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Database: UniProt
Entry: RYR1_HUMAN
LinkDB: RYR1_HUMAN
Original site: RYR1_HUMAN 
ID   RYR1_HUMAN              Reviewed;        5038 AA.
AC   P21817; Q16314; Q16368; Q9NPK1; Q9P1U4;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   13-JUN-2006, sequence version 3.
DT   30-AUG-2017, entry version 203.
DE   RecName: Full=Ryanodine receptor 1;
DE            Short=RYR-1;
DE            Short=RyR1;
DE   AltName: Full=Skeletal muscle calcium release channel;
DE   AltName: Full=Skeletal muscle ryanodine receptor;
DE   AltName: Full=Skeletal muscle-type ryanodine receptor;
DE   AltName: Full=Type 1 ryanodine receptor;
GN   Name=RYR1; Synonyms=RYDR;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Skeletal muscle;
RX   PubMed=2298749;
RA   Zorzato F., Fujii J., Otsu K., Phillips M.S., Green N.M., Lai F.A.,
RA   Meissner G., Maclennan D.H.;
RT   "Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+
RT   release channel (ryanodine receptor) of skeletal muscle sarcoplasmic
RT   reticulum.";
RL   J. Biol. Chem. 265:2244-2256(1990).
RN   [2]
RP   SEQUENCE REVISION TO 2324; 2840 AND 3380, INVOLVEMENT IN MHS1, VARIANT
RP   MHS1 ARG-248, AND VARIANTS CYS-471; LEU-1787; CYS-2060 AND VAL-2550.
RC   TISSUE=Muscle;
RX   PubMed=1354642; DOI=10.1016/0888-7543(92)90042-Q;
RA   Gillard E.F., Otsu K., Fujii J., Duff C.L., de Leon S., Khanna V.K.,
RA   Britt B.A., Worton R.G., McLennan D.H.;
RT   "Polymorphisms and deduced amino acid substitutions in the coding
RT   sequence of the ryanodine receptor (RYR1) gene in individuals with
RT   malignant hyperthermia.";
RL   Genomics 13:1247-1254(1992).
RN   [3]
RP   SEQUENCE REVISION TO 1365-1368, VARIANT CCD HIS-2435, AND ALTERNATIVE
RP   SPLICING.
RC   TISSUE=Muscle;
RX   PubMed=8220422; DOI=10.1038/ng0993-46;
RA   Zhang Y., Chen H.S., Khanna V.K., de Leon S., Phillips M.S.,
RA   Schappert K.T., Britt B.A., Brownell A.K.W., McLennan D.H.;
RT   "A mutation in the human ryanodine receptor gene associated with
RT   central core disease.";
RL   Nat. Genet. 5:46-50(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANTS
RP   ALA-1832 AND VAL-2550.
RX   PubMed=8661021; DOI=10.1006/geno.1996.0238;
RA   Phillips M.S., Fujii J., Khanna V.K., de Leon S., Yokobata K.,
RA   de Jong P.J., McLennan D.H.;
RT   "The structural organization of the human skeletal muscle ryanodine
RT   receptor (RYR1) gene.";
RL   Genomics 34:24-41(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 598-722.
RC   TISSUE=Skeletal muscle;
RX   PubMed=1639409; DOI=10.1016/0888-7543(92)90163-M;
RA   Otsu K., Phillips M.S., Khanna V.K., de Leon S., McLennan D.H.;
RT   "Refinement of diagnostic assays for a probable causal mutation for
RT   porcine and human malignant hyperthermia.";
RL   Genomics 13:835-837(1992).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 603-641, AND VARIANT MHS1
RP   CYS-614.
RX   PubMed=1774074; DOI=10.1016/0888-7543(91)90084-R;
RA   Gillard E.F., Otsu K., Fujii J., Khanna V.K., de Leon S.,
RA   Derdemezi J., Britt B.A., Duff C.L., Worton R.G., MacLennan D.H.;
RT   "A substitution of cysteine for arginine 614 in the ryanodine receptor
RT   is potentially causative of human malignant hyperthermia.";
RL   Genomics 11:751-755(1991).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 603-627, AND VARIANT MHS1
RP   CYS-614.
RX   PubMed=7751854; DOI=10.1007/BF00936884;
RA   Moroni I., Gonano E.F., Comi G.P., Tegazzin V., Prelle A., Bordoni A.,
RA   Bresolin N., Scarlato G.;
RT   "Ryanodine receptor gene point mutation and malignant hyperthermia
RT   susceptibility.";
RL   J. Neurol. 242:127-133(1995).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4696-4974, AND SUBCELLULAR LOCATION.
RC   TISSUE=Myometrium;
RX   PubMed=7556644; DOI=10.1016/0014-5793(95)00924-X;
RA   Lynn S., Morgan J.M., Lamb H.K., Meissner G., Gillespie J.I.;
RT   "Isolation and partial cloning of ryanodine-sensitive Ca2+ release
RT   channel protein isoforms from human myometrial smooth muscle.";
RL   FEBS Lett. 372:6-12(1995).
RN   [10]
RP   TISSUE SPECIFICITY.
RX   PubMed=9607712; DOI=10.1016/S0306-4522(97)00612-X;
RA   Martin C., Chapman K.E., Seckl J.R., Ashley R.H.;
RT   "Partial cloning and differential expression of ryanodine
RT   receptor/calcium-release channel genes in human tissues including the
RT   hippocampus and cerebellum.";
RL   Neuroscience 85:205-216(1998).
RN   [11]
RP   INTERACTION WITH CALM AND S100A1, AND ENZYME REGULATION.
RX   PubMed=18650434; DOI=10.1074/jbc.M804432200;
RA   Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F.,
RA   Weber D.J.;
RT   "S100A1 and calmodulin compete for the same binding site on ryanodine
RT   receptor.";
RL   J. Biol. Chem. 283:26676-26683(2008).
RN   [12]
RP   FUNCTION, PHOSPHORYLATION AT SER-2843, S-NITROSYLATION, AND
RP   IDENTIFICATION IN A COMPLEX WITH PDE4D; PKA; FKBP1A AND PROTEIN
RP   PHOSPHATASE 1.
RX   PubMed=18268335; DOI=10.1073/pnas.0711074105;
RA   Bellinger A.M., Reiken S., Dura M., Murphy P.W., Deng S.X.,
RA   Landry D.W., Nieman D., Lehnart S.E., Samaru M., LaCampagne A.,
RA   Marks A.R.;
RT   "Remodeling of ryanodine receptor complex causes 'leaky' channels: a
RT   molecular mechanism for decreased exercise capacity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:2198-2202(2008).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-4864 AND SER-4867, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=18318008; DOI=10.1002/pmic.200700884;
RA   Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA   Zou H., Gu J.;
RT   "Large-scale phosphoproteome analysis of human liver tissue by
RT   enrichment and fractionation of phosphopeptides with strong anion
RT   exchange chromatography.";
RL   Proteomics 8:1346-1361(2008).
RN   [14]
RP   REVIEW.
RX   PubMed=20961976; DOI=10.1101/cshperspect.a003996;
RA   Lanner J.T., Georgiou D.K., Joshi A.D., Hamilton S.L.;
RT   "Ryanodine receptors: structure, expression, molecular details, and
RT   function in calcium release.";
RL   Cold Spring Harb. Perspect. Biol. 2:E3996-E3996(2010).
RN   [15]
RP   INVOLVEMENT IN SAMARITAN MYOPATHY, AND VARIANT CYS-1088.
RX   PubMed=22752422; DOI=10.1007/s00401-012-1007-3;
RA   Bohm J., Leshinsky-Silver E., Vassilopoulos S., Le Gras S.,
RA   Lerman-Sagie T., Ginzberg M., Jost B., Lev D., Laporte J.;
RT   "Samaritan myopathy, an ultimately benign congenital myopathy, is
RT   caused by a RYR1 mutation.";
RL   Acta Neuropathol. 124:575-581(2012).
RN   [16]
RP   VARIANTS CCD CYS-163 AND MET-403, AND VARIANTS MHS1 CYS-163 AND
RP   MET-403.
RX   PubMed=8220423; DOI=10.1038/ng0993-51;
RA   Quane K.A., Healy J.M.S., Keating K.E., Manning B.M., Couch F.J.,
RA   Palmucci L.M., Doriguzzi C., Fagerlund T.H., Berg K., Ording H.,
RA   Bendixen D., Mortier W., Linz U., Muller C.R., McCarthy T.V.;
RT   "Mutations in the ryanodine receptor gene in central core disease and
RT   malignant hyperthermia.";
RL   Nat. Genet. 5:51-55(1993).
RN   [17]
RP   VARIANT CCD SER-522.
RX   PubMed=7829078; DOI=10.1006/geno.1994.1483;
RA   Quane K.A., Keating K.E., Healy J.M.S., Manning B.M.,
RA   Krivosic-Horber R., Krivosic I., Monnier N., Lunardi J.,
RA   McCarthy T.V.;
RT   "Mutation screening of the RYR1 gene in malignant hyperthermia:
RT   detection of a novel Tyr to Ser mutation in a pedigree with associated
RT   central cores.";
RL   Genomics 23:236-239(1994).
RN   [18]
RP   VARIANT MHS1 ARG-341.
RX   PubMed=8012359; DOI=10.1093/hmg/3.3.471;
RA   Quane K.A., Keating K.E., Manning B.M., Healy J.M.S., Monsieurs K.,
RA   Heffron J.J.A., Lehane M., Heytens L., Krivosic-Horber R., Adnet P.,
RA   Ellis F.R., Monnier N., Lunardi J., McCarthy T.V.;
RT   "Detection of a novel common mutation in the ryanodine receptor gene
RT   in malignant hyperthermia: implications for diagnosis and
RT   heterogeneity studies.";
RL   Hum. Mol. Genet. 3:471-476(1994).
RN   [19]
RP   VARIANT MHS1 ARG-2434.
RX   PubMed=7849712; DOI=10.1093/hmg/3.10.1855;
RA   Keating K.E., Quane K.A., Manning B.M., Lehane M., Hartung E.,
RA   Censier K., Urwyler A., Klausnitzer M., Muller C.R., Heffron J.J.A.,
RA   McCarthy T.V.;
RT   "Detection of a novel RYR1 mutation in four malignant hyperthermia
RT   pedigrees.";
RL   Hum. Mol. Genet. 3:1855-1858(1994).
RN   [20]
RP   VARIANT MHS1 ARG-2434.
RX   PubMed=7881417; DOI=10.1093/hmg/3.12.2181;
RA   Phillips M.S., Khanna V.K., de Leon S., Frodis W., Britt B.A.,
RA   McLennan D.H.;
RT   "The substitution of Arg for Gly2433 in the human skeletal muscle
RT   ryanodine receptor is associated with malignant hyperthermia.";
RL   Hum. Mol. Genet. 3:2181-2186(1994).
RN   [21]
RP   VARIANT MHS1 ARG-35.
RX   PubMed=9066328; DOI=10.1097/00000542-199703000-00014;
RA   Lynch P.J., Krivosic-Horber R., Reyford H., Monnier N., Quane K.A.,
RA   Adnet P., Haudecoeur G., Krivosic I., McCarthy T.V., Lunardi J.;
RT   "Identification of heterozygous and homozygous individuals with the
RT   novel RYR1 mutation Cys35Arg in a large kindred.";
RL   Anesthesiology 86:620-626(1997).
RN   [22]
RP   VARIANT MHS1 LEU-614.
RX   PubMed=9389851; DOI=10.1093/bja/79.3.332;
RA   Quane K.A., Ording H., Keating K.E., Manning B.M., Heine R.,
RA   Bendixen D., Berg K., Krivosic-Horber R., Lehmann-Horn F.,
RA   Fagerlund T.H., McCarthy T.V.;
RT   "Detection of a novel mutation at amino acid position 614 in the
RT   ryanodine receptor in malignant hyperthermia.";
RL   Br. J. Anaesth. 79:332-337(1997).
RN   [23]
RP   VARIANT MHS1 TRP-552.
RX   PubMed=9138151; DOI=10.1136/jmg.34.4.291;
RA   Keating K.E., Giblin L., Lynch P.J., Quane K.A., Lehane M.,
RA   Heffron J.J.A., McCarthy T.V.;
RT   "Detection of a novel mutation in the ryanodine receptor gene in an
RT   Irish malignant hyperthermia pedigree: correlation of the IVCT
RT   response with the affected and unaffected haplotypes.";
RL   J. Med. Genet. 34:291-296(1997).
RN   [24]
RP   VARIANTS MHS1 CYS-2163; MET-2168 AND MET-2206, AND VARIANT CCD/MHS1
RP   HIS-2163.
RX   PubMed=9497245; DOI=10.1086/301748;
RA   Manning B.M., Quane K.A., Ording H., Urwyler A., Tegazzin V.,
RA   Lehane M., O'Halloran J., Hartung E., Giblin L.M., Lynch P.J.,
RA   Vaughan P., Censier K., Bendixen D., Comi G.P., Heytens L.,
RA   Monsieurs K., Fagerlund T.H., Wolz W., Heffron J.J.A., Mueller C.R.,
RA   McCarthy T.V.;
RT   "Identification of novel mutations in the ryanodine-receptor gene
RT   (RYR1) in malignant hyperthermia: genotype-phenotype correlation.";
RL   Am. J. Hum. Genet. 62:599-609(1998).
RN   [25]
RP   VARIANTS MHS1 CYS-2458 AND HIS-2458.
RX   PubMed=9450902;
RX   DOI=10.1002/(SICI)1098-1004(1998)11:1<45::AID-HUMU7>3.3.CO;2-H;
RA   Manning B.M., Quane K.A., Lynch P.J., Urwyler A., Tegazzin V.,
RA   Krivosic-Horber R., Censier K., Comi G.P., Adnet P., Wolz W.,
RA   Lunardi J., Muller C.R., McCarthy T.V.;
RT   "Novel mutations at a CpG dinucleotide in the ryanodine receptor in
RT   malignant hyperthermia.";
RL   Hum. Mutat. 11:45-50(1998).
RN   [26]
RP   VARIANTS MHS1.
RX   PubMed=10484775; DOI=10.1093/hmg/8.11.2055;
RA   Brandt A., Schleithoff L., Jurkat-Rott K., Klingler W., Baur C.,
RA   Lehmann-Horn F.;
RT   "Screening of the ryanodine receptor gene in 105 malignant
RT   hyperthermia families: novel mutations and concordance with the in
RT   vitro contracture test.";
RL   Hum. Mol. Genet. 8:2055-2062(1999).
RN   [27]
RP   VARIANTS MHS1 LEU-2435 AND HIS-2454.
RX   PubMed=10051009;
RA   Barone V., Massa O., Intravaia E., Bracco A., Di Martino A.,
RA   Tegazzin V., Cozzolino S., Sorrentino V.;
RT   "Mutation screening of the RYR1 gene and identification of two novel
RT   mutations in Italian malignant hyperthermia families.";
RL   J. Med. Genet. 36:115-118(1999).
RN   [28]
RP   VARIANT CCD THR-4898, AND CHARACTERIZATION OF VARIANT CCD THR-4898.
RX   PubMed=10097181; DOI=10.1073/pnas.96.7.4164;
RA   Lynch P.J., Tong J., Lehane M., Mallet A., Giblin L., Heffron J.J.A.,
RA   Vaughan P., Zafra G., MacLennan D.H., McCarthy T.V.;
RT   "A mutation in the transmembrane/luminal domain of the ryanodine
RT   receptor is associated with abnormal Ca(2+) release channel function
RT   and severe central core disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:4164-4169(1999).
RN   [29]
RP   VARIANTS MHS1 TRP-2452 AND HIS-2454.
RX   PubMed=10823104; DOI=10.1093/oxfordjournals.bja.a013478;
RA   Chamley D., Pollock N.A., Stowell K.M., Brown R.L.;
RT   "Malignant hyperthermia in infancy and identification of novel RYR1
RT   mutation.";
RL   Br. J. Anaesth. 84:500-504(2000).
RN   [30]
RP   VARIANT MHS1 ILE-4826.
RX   PubMed=10888602; DOI=10.1093/hmg/9.10.1515;
RA   Brown R.L., Pollock A.N., Couchman K.G., Hodges M., Hutchinson D.O.,
RA   Waaka R., Lynch P., McCarthy T.V., Stowell K.M.;
RT   "A novel ryanodine receptor mutation and genotype-phenotype
RT   correlation in a large malignant hyperthermia New Zealand Maori
RT   pedigree.";
RL   Hum. Mol. Genet. 9:1515-1524(2000).
RN   [31]
RP   VARIANT MHS1 CYS-2454.
RX   PubMed=10612851;
RX   DOI=10.1002/(SICI)1098-1004(200001)15:1<122::AID-HUMU40>3.0.CO;2-A;
RA   Gencik M., Gencik A., Mortier W., Epplen J.T.;
RT   "Novel mutation in the RYR1 gene (R2454C) in a patient with malignant
RT   hyperthermia.";
RL   Hum. Mutat. 15:122-122(2000).
RN   [32]
RP   VARIANT CCD ALA-4637.
RX   PubMed=11113224; DOI=10.1212/WNL.55.11.1689;
RA   Scacheri P.C., Hoffman E.P., Fratkin J.D., Semino-Mora C., Senchak A.,
RA   Davis M.R., Laing N.G., Vedanarayanan V., Subramony S.H.;
RT   "A novel ryanodine receptor gene mutation causing both cores and rods
RT   in congenital myopathy.";
RL   Neurology 55:1689-1696(2000).
RN   [33]
RP   VARIANT MHS1 GLU-2347 DEL.
RX   PubMed=11389482; DOI=10.1086/321270;
RA   Sambuughin N., McWilliams S., de Bantel A., Sivakumar K., Nelson T.E.;
RT   "Single-amino-acid deletion in the RYR1 gene, associated with
RT   malignant hyperthermia susceptibility and unusual contraction
RT   phenotype.";
RL   Am. J. Hum. Genet. 69:204-208(2001).
RN   [34]
RP   VARIANTS MHS1 CYS-163; ARG-248; CYS-614; MET-2168; MET-2206; ILE-2214;
RP   THR-2367; ASN-2431; ARG-2434 AND HIS-2454.
RX   PubMed=11575529; DOI=10.1097/00000542-200109000-00009;
RA   Sambuughin N., Sei Y., Gallagher K.L., Wyre H.W., Madsen D.,
RA   Nelson T.E., Fletcher J.E., Rosenberg H., Muldoon S.M.;
RT   "North American malignant hyperthermia population: screening of the
RT   ryanodine receptor gene and identification of novel mutations.";
RL   Anesthesiology 95:594-599(2001).
RN   [35]
RP   VARIANTS CCD MET-2168; 4214-ARG--4216-PHE DEL; 4647-LEU-SER-4648 DEL;
RP   PRO-4793; CYS-4796; CYS-4825; PHE-4860 DEL; HIS-4861; TRP-4893;
RP   THR-4898; GLU-4899 AND GLY-4914.
RX   PubMed=11709545; DOI=10.1093/hmg/10.22.2581;
RA   Monnier N., Romero N.B., Lerale J., Landrieu P., Nivoche Y.,
RA   Fardeau M., Lunardi J.;
RT   "Familial and sporadic forms of central core disease are associated
RT   with mutations in the C-terminal domain of the skeletal muscle
RT   ryanodine receptor.";
RL   Hum. Mol. Genet. 10:2581-2592(2001).
RN   [36]
RP   VARIANTS CCD HIS-4861; ARG-4891; THR-4898; ARG-4899 AND VAL-4906,
RP   CHARACTERIZATION OF VARIANTS CCD MET-2168; HIS-4861; TRP-4893;
RP   THR-4898 AND ARG-4899, AND FUNCTION.
RX   PubMed=11741831; DOI=10.1093/hmg/10.25.2879;
RA   Tilgen N., Zorzato F., Halliger-Keller B., Muntoni F., Sewry C.,
RA   Palmucci L.M., Schneider C., Hauser E., Lehmann-Horn F., Mueller C.R.,
RA   Treves S.;
RT   "Identification of four novel mutations in the C-terminal membrane
RT   spanning domain of the ryanodine receptor 1: association with central
RT   core disease and alteration of calcium homeostasis.";
RL   Hum. Mol. Genet. 10:2879-2887(2001).
RN   [37]
RP   VARIANT MHS1 GLU-2129.
RX   PubMed=11241852; DOI=10.1002/humu.15;
RA   Rueffert H., Kraus H., Olthoff D., Deutrich C., Froster U.G.;
RT   "Identification of a novel mutation in the ryanodine receptor gene
RT   (RYR1) in patients with malignant hyperthermia.";
RL   Hum. Mutat. 17:238-238(2001).
RN   [38]
RP   VARIANT MHS1 THR-2350, AND CHARACTERIZATION OF VARIANT MHS1 THR-2350.
RX   PubMed=11525881; DOI=10.1016/S0960-8966(01)00202-4;
RA   Sambuughin N., Nelson T.E., Jankovic J., Xin C., Meissner G.,
RA   Mullakandov M., Ji J., Rosenberg H., Sivakumar K., Goldfarb L.G.;
RT   "Identification and functional characterization of a novel ryanodine
RT   receptor mutation causing malignant hyperthermia in North American and
RT   South American families.";
RL   Neuromuscul. Disord. 11:530-537(2001).
RN   [39]
RP   VARIANTS MHS1 CYS-163; ASN-166; ARG-341; HIS-401; CYS-614; GLU-2129;
RP   MET-2168; MET-2206; THR-2428; ARG-2434; HIS-2435; TRP-2452 AND
RP   HIS-2454.
RX   PubMed=12059893; DOI=10.1034/j.1399-6576.2002.460610.x;
RA   Rueffert H., Olthoff D., Deutrich C., Meinecke C.D., Froster U.G.;
RT   "Mutation screening in the ryanodine receptor 1 gene (RYR1) in
RT   patients susceptible to malignant hyperthermia who show definite IVCT
RT   results: identification of three novel mutations.";
RL   Acta Anaesthesiol. Scand. 46:692-698(2002).
RN   [40]
RP   VARIANTS MHS1 CYS-163; ARG-341; CYS-614; CYS-2454; MET-3916 AND
RP   LEU-4973.
RX   PubMed=12411788; DOI=10.1097/00000542-200211000-00007;
RA   Monnier N., Krivosic-Horber R., Payen J.-F., Kozak-Ribbens G.,
RA   Nivoche Y., Adnet P., Reyford H., Lunardi J.;
RT   "Presence of two different genetic traits in malignant hyperthermia
RT   families: implication for genetic analysis, diagnosis, and incidence
RT   of malignant hyperthermia susceptibility.";
RL   Anesthesiology 97:1067-1074(2002).
RN   [41]
RP   VARIANT CCD SER-3527.
RX   PubMed=12112081; DOI=10.1002/ana.10231;
RA   Ferreiro A., Monnier N., Romero N.B., Leroy J.-P., Boennemann C.,
RA   Haenggeli C.-A., Straub V., Voss W.D., Nivoche Y., Jungbluth H.,
RA   Lemainque A., Voit T., Lunardi J., Fardeau M., Guicheney P.;
RT   "A recessive form of central core disease, transiently presenting as
RT   multi-minicore disease, is associated with a homozygous mutation in
RT   the ryanodine receptor type 1 gene.";
RL   Ann. Neurol. 51:750-759(2002).
RN   [42]
RP   VARIANT MHS1 CYS-401.
RX   PubMed=12066726; DOI=10.1093/bja/88.4.508;
RA   Davis M., Brown R., Dickson A., Horton H., James D., Laing N.,
RA   Marston R., Norgate M., Perlman D., Pollock N., Stowell K.;
RT   "Malignant hyperthermia associated with exercise-induced
RT   rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation
RT   in New Zealand and Australian pedigrees.";
RL   Br. J. Anaesth. 88:508-515(2002).
RN   [43]
RP   VARIANTS MHS1 CYS-163; CYS-401; HIS-2163; MET-2206; ILE-2280;
RP   ARG-2434; LEU-2435; CYS-2458; SER-4136; LEU-4234; TRP-4737; VAL-4942
RP   AND LEU-4973.
RX   PubMed=12208234; DOI=10.1016/S0143-4160(02)00138-0;
RA   Galli L., Orrico A., Cozzolino S., Pietrini V., Tegazzin V.,
RA   Sorrentino V.;
RT   "Mutations in the RYR1 gene in Italian patients at risk for malignant
RT   hyperthermia: evidence for a cluster of novel mutations in the C-
RT   terminal region.";
RL   Cell Calcium 32:143-151(2002).
RN   [44]
RP   VARIANT MHS1 CYS-2355.
RX   PubMed=12123492; DOI=10.1034/j.1399-0004.2002.620111.x;
RA   McWilliams S., Nelson T., Sudo R.T., Zapata-Sudo G., Batti M.,
RA   Sambuughin N.;
RT   "Novel skeletal muscle ryanodine receptor mutation in a large
RT   Brazilian family with malignant hyperthermia.";
RL   Clin. Genet. 62:80-83(2002).
RN   [45]
RP   VARIANT MHS1 VAL-4838, AND VARIANTS ALA-1832; GLU-3756 AND SER-4668.
RX   PubMed=11928716; DOI=10.1254/jjp.88.159;
RA   Oyamada H., Oguchi K., Saitoh N., Yamazawa T., Hirose K., Kawana Y.,
RA   Wakatsuki K., Oguchi K., Tagami M., Hanaoka K., Endo M., Iino M.;
RT   "Novel mutations in C-terminal channel region of the ryanodine
RT   receptor in malignant hyperthermia patients.";
RL   Jpn. J. Pharmacol. 88:159-166(2002).
RN   [46]
RP   VARIANT CCD ILE-4849.
RX   PubMed=12136074; DOI=10.1212/WNL.59.2.284;
RA   Jungbluth H., Muller C.R., Halliger-Keller B., Brockington M.,
RA   Brown S.C., Feng L., Chattopadhyay A., Mercuri E., Manzur A.Y.,
RA   Ferreiro A., Laing N.G., Davis M.R., Roper H.P., Dubowitz V.,
RA   Bydder G., Sewry C.A., Muntoni F.;
RT   "Autosomal recessive inheritance of RYR1 mutations in a congenital
RT   myopathy with cores.";
RL   Neurology 59:284-287(2002).
RN   [47]
RP   VARIANT MHS1 TRP-328, AND CHARACTERIZATION OF VARIANT MHS1 TRP-328.
RX   PubMed=12883402; DOI=10.1097/00000542-200308000-00011;
RA   Loke J.C.P., Kraev N., Sharma P., Du G., Patel L., Kraev A.,
RA   MacLennan D.H.;
RT   "Detection of a novel ryanodine receptor subtype 1 mutation (R328W) in
RT   a malignant hyperthermia family by sequencing of a leukocyte
RT   transcript.";
RL   Anesthesiology 99:297-302(2003).
RN   [48]
RP   VARIANTS CCD HIS-4861; CYS-4864; TRP-4893 AND THR-4940.
RX   PubMed=14670767; DOI=10.1136/adc.88.12.1051;
RA   Quinlivan R.M., Muller C.R., Davis M., Laing N.G., Evans G.A.,
RA   Dwyer J., Dove J., Roberts A.P., Sewry C.A.;
RT   "Central core disease: clinical, pathological, and genetic features.";
RL   Arch. Dis. Child. 88:1051-1055(2003).
RN   [49]
RP   VARIANTS CCD GLU-215; CYS-614; PRO-4650; GLN-4724 AND GLU-4899.
RX   PubMed=12937085; DOI=10.1093/brain/awg244;
RA   Romero N.B., Monnier N., Viollet L., Cortey A., Chevallay M.,
RA   Leroy J.P., Lunardi J., Fardeau M.;
RT   "Dominant and recessive central core disease associated with RYR1
RT   mutations and fetal akinesia.";
RL   Brain 126:2341-2349(2003).
RN   [50]
RP   VARIANTS MHS1 CYS-44; CYS-533; LEU-2117; PRO-2163; MET-2168; LEU-2435
RP   AND HIS-2454, AND VARIANT LYS-2101.
RX   PubMed=12709367; DOI=10.1373/49.5.761;
RA   Tammaro A., Bracco A., Cozzolino S., Esposito M., Di Martino A.,
RA   Savoia G., Zeuli L., Piluso G., Aurino S., Nigro V.;
RT   "Scanning for mutations of the ryanodine receptor (RYR1) gene by
RT   denaturing HPLC: detection of three novel malignant hyperthermia
RT   alleles.";
RL   Clin. Chem. 49:761-768(2003).
RN   [51]
RP   VARIANT CCD 4863-ARG--ASP-4869 DELINS TYR.
RX   PubMed=12566385; DOI=10.1093/hmg/ddg032;
RA   Zorzato F., Yamaguchi N., Xu L., Meissner G., Mueller C.R.,
RA   Pouliquin P., Muntoni F., Sewry C., Girard T., Treves S.;
RT   "Clinical and functional effects of a deletion in a COOH-terminal
RT   lumenal loop of the skeletal muscle ryanodine receptor.";
RL   Hum. Mol. Genet. 12:379-388(2003).
RN   [52]
RP   INVOLVEMENT IN MMDO.
RX   PubMed=12719381; DOI=10.1093/hmg/ddg121;
RA   Monnier N., Ferreiro A., Marty I., Labarre-Vila A., Mezin P.,
RA   Lunardi J.;
RT   "A homozygous splicing mutation causing a depletion of skeletal muscle
RT   RYR1 is associated with multi-minicore disease congenital myopathy
RT   with ophthalmoplegia.";
RL   Hum. Mol. Genet. 12:1171-1178(2003).
RN   [53]
RP   VARIANT CORE/ROD DISEASE ILE-4637, AND VARIANTS CCD ASP-4638;
RP   PRO-4651; CYS-4861; HIS-4861; GLN-4893; THR-4898; GLY-4914; THR-4914;
RP   4927-VAL-ILE-4928 DEL AND THR-4940.
RX   PubMed=12565913; DOI=10.1016/S0960-8966(02)00218-3;
RA   Davis M.R., Haan E., Jungbluth H., Sewry C., North K., Muntoni F.,
RA   Kuntzer T., Lamont P., Bankier A., Tomlinson P., Sanchez A., Walsh P.,
RA   Nagarajan L., Oley C., Colley A., Gedeon A., Quinlivan R., Dixon J.,
RA   James D., Mueller C.R., Laing N.G.;
RT   "Principal mutation hotspot for central core disease and related
RT   myopathies in the C-terminal transmembrane region of the RYR1 gene.";
RL   Neuromuscul. Disord. 13:151-157(2003).
RN   [54]
RP   VARIANTS MHS1 CYS-163; ARG-248; CYS-614; CYS-2163; MET-2168; MET-2206;
RP   ILE-2214; THR-2350; THR-2367; ASN-2431; ARG-2434; VAL-2437; HIS-2454
RP   AND PRO-4824.
RX   PubMed=15448513; DOI=10.1097/00000542-200410000-00005;
RA   Sei Y., Sambuughin N.N., Davis E.J., Sachs D., Cuenca P.B.,
RA   Brandom B.W., Tautz T., Rosenberg H., Nelson T.E., Muldoon S.M.;
RT   "Malignant hyperthermia in North America: genetic screening of the
RT   three hot spots in the type I ryanodine receptor gene.";
RL   Anesthesiology 101:824-830(2004).
RN   [55]
RP   VARIANTS MHS1 TRP-2676 AND SER-2787.
RX   PubMed=14732627; DOI=10.1001/archneur.61.1.106;
RA   Guis S., Figarella-Branger D., Monnier N., Bendahan D.,
RA   Kozak-Ribbens G., Mattei J.-P., Lunardi J., Cozzone P.J.,
RA   Pellissier J.-F.;
RT   "Multiminicore disease in a family susceptible to malignant
RT   hyperthermia: histology, in vitro contracture tests, and genetic
RT   characterization.";
RL   Arch. Neurol. 61:106-113(2004).
RN   [56]
RP   VARIANTS CCD GLY-160; ASP-4638; PHE-4814; HIS-4861 AND MET-4938, AND
RP   VARIANTS MHS1 CYS-614; MET-2346; GLY-2348; TRP-2452; HIS-2458;
RP   PRO-4824 AND GLU-4939.
RX   PubMed=14985404; DOI=10.1136/jmg.2003.014274;
RA   Shepherd S., Ellis F., Halsall J., Hopkins P., Robinson R.;
RT   "RYR1 mutations in UK central core disease patients: more than just
RT   the C-terminal transmembrane region of the RYR1 gene.";
RL   J. Med. Genet. 41:E33-E33(2004).
RN   [57]
RP   VARIANT MHS1 SER-2342.
RX   PubMed=15221887; DOI=10.1002/mus.20068;
RA   Marchant C.L., Ellis F.R., Halsall P.J., Hopkins P.M., Robinson R.L.;
RT   "Mutation analysis of two patients with hypokalemic periodic paralysis
RT   and suspected malignant hyperthermia.";
RL   Muscle Nerve 30:114-117(2004).
RN   [58]
RP   VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-165; ASN-166; CYS-177;
RP   CYS-178; VAL-227; ARG-248; TRP-328; ARG-341; SER-401; HIS-401;
RP   MET-403; SER-522; TRP-552; CYS-614; LEU-614; CYS-2163; HIS-2163;
RP   MET-2168; MET-2206; ARG-2206; ASP-2344; MET-2346; THR-2350; THR-2428;
RP   ARG-2434; HIS-2435; CYS-2454; HIS-2454; CYS-2458; TRP-2676; SER-2787;
RP   MET-3916; SER-4684; GLN-4737; TRP-4737; ILE-4826; VAL-4838; ILE-4849;
RP   ARG-4876; GLU-4939 AND LEU-4973, CHARACTERIZATION OF VARIANTS MHS1
RP   LEU-163; MET-2206; THR-2428; CYS-2454 AND HIS-2454, FUNCTION, AND
RP   ENZYME REGULATION.
RX   PubMed=16163667; DOI=10.1002/humu.20231;
RA   Monnier N., Kozak-Ribbens G., Krivosic-Horber R., Nivoche Y., Qi D.,
RA   Kraev N., Loke J., Sharma P., Tegazzin V., Figarella-Branger D.,
RA   Romero N., Mezin P., Bendahan D., Payen J.-F., Depret T.,
RA   Maclennan D.H., Lunardi J.;
RT   "Correlations between genotype and pharmacological, histological,
RT   functional, and clinical phenotypes in malignant hyperthermia
RT   susceptibility.";
RL   Hum. Mutat. 26:413-425(2005).
RN   [59]
RP   VARIANTS MMDO TRP-109 AND LYS-2423, AND VARIANTS VAL-485 AND CYS-2060.
RX   PubMed=16380615; DOI=10.1212/01.wnl.0000188870.37076.f2;
RA   Jungbluth H., Zhou H., Hartley L., Halliger-Keller B., Messina S.,
RA   Longman C., Brockington M., Robb S.A., Straub V., Voit T., Swash M.,
RA   Ferreiro A., Bydder G., Sewry C.A., Mueller C., Muntoni F.;
RT   "Minicore myopathy with ophthalmoplegia caused by mutations in the
RT   ryanodine receptor type 1 gene.";
RL   Neurology 65:1930-1935(2005).
RN   [60]
RP   VARIANT CCD VAL-4846.
RX   PubMed=17204054; DOI=10.1111/j.1399-0004.2006.00725.x;
RA   Gambelli S., Malandrini A., Berti G., Gaudiano C., Zicari E.,
RA   Brunori P., Perticoni G., Orrico A., Galli L., Sorrentino V.,
RA   Lunardi J., Federico A., Dotti M.T.;
RT   "Inheritance of a novel RYR1 mutation in a family with myotonic
RT   dystrophy type 1.";
RL   Clin. Genet. 71:93-94(2007).
RN   [61]
RP   VARIANTS CCD GLN-4558; VAL-4846; ILE-4849; HIS-4861; CYS-4861;
RP   VAL-4897 AND THR-4914.
RX   PubMed=17226826; DOI=10.1002/mus.20715;
RA   Kossugue P.M., Paim J.F., Navarro M.M., Silva H.C., Pavanello R.C.M.,
RA   Gurgel-Giannetti J., Zatz M., Vainzof M.;
RT   "Central core disease due to recessive mutations in RYR1 gene: is it
RT   more common than described?";
RL   Muscle Nerve 35:670-674(2007).
RN   [62]
RP   VARIANT CCD MET-4882.
RX   PubMed=18312400; DOI=10.1111/j.1468-1331.2008.02094.x;
RA   von der Hagen M., Kress W., Hahn G., Brocke K.S., Mitzscherling P.,
RA   Huebner A., Muller-Reible C., Stoltenburg-Didinger G., Kaindl A.M.;
RT   "Novel RYR1 missense mutation causes core rod myopathy.";
RL   Eur. J. Neurol. 15:E31-E32(2008).
RN   [63]
RP   VARIANTS CCD VAL-13; SER-1704; PRO-2421; LYS-2423; HIS-3539; GLN-3772;
RP   GLN-4558; MET-4842 AND ILE-4849.
RX   PubMed=18253926; DOI=10.1002/humu.20696;
RA   Monnier N., Marty I., Faure J., Castiglioni C., Desnuelle C.,
RA   Sacconi S., Estournet B., Ferreiro A., Romero N., Laquerriere A.,
RA   Lazaro L., Martin J.-J., Morava E., Rossi A., Van der Kooi A.,
RA   de Visser M., Verschuuren C., Lunardi J.;
RT   "Null mutations causing depletion of the type 1 ryanodine receptor
RT   (RYR1) are commonly associated with recessive structural congenital
RT   myopathies with cores.";
RL   Hum. Mutat. 29:670-678(2008).
RN   [64]
RP   VARIANTS MHS1 ARG-13; LYS-226; LEU-367; HIS-530; TYR-544; CYS-1043;
RP   GLY-1352; HIS-2336; LYS-2404; TRP-2676; GLY-2730; SER-2787; LYS-2880;
RP   PRO-3217; LYS-3290; TRP-3772; ARG-3806; LEU-4501; VAL-4838; ARG-4876
RP   AND THR-4938, AND VARIANTS GLY-1342; LEU-1787; ALA-1832; CYS-2060;
RP   VAL-2321; VAL-2550; GLN-3583 AND GLU-3756.
RX   PubMed=19191329; DOI=10.1002/humu.20878;
RA   Levano S., Vukcevic M., Singer M., Matter A., Treves S., Urwyler A.,
RA   Girard T.;
RT   "Increasing the number of diagnostic mutations in malignant
RT   hyperthermia.";
RL   Hum. Mutat. 30:590-598(2009).
RN   [65]
RP   VARIANT MHS1 CYS-2508, AND CHARACTERIZATION OF VARIANT MHS1 CYS-2508.
RX   PubMed=19685112; DOI=10.1007/s00540-009-0746-3;
RA   Migita T., Mukaida K., Hamada H., Yasuda T., Haraki T., Nishino I.,
RA   Murakami N., Kawamoto M.;
RT   "Functional analysis of ryanodine receptor type 1 p.R2508C mutation in
RT   exon 47.";
RL   J. Anesth. 23:341-346(2009).
RN   [66]
RP   VARIANTS MHS1 ASN-382; LYS-1058 AND ARG-1393, VARIANT CCD GLY-2508,
RP   AND VARIANT HIS-1679.
RX   PubMed=20142353; DOI=10.1213/ANE.0b013e3181cbd815;
RA   Vukcevic M., Broman M., Islander G., Bodelsson M., Ranklev-Twetman E.,
RA   Muller C.R., Treves S.;
RT   "Functional properties of RYR1 mutations identified in Swedish
RT   patients with malignant hyperthermia and central core disease.";
RL   Anesth. Analg. 111:185-190(2010).
RN   [67]
RP   VARIANTS MMDO THR-402; LEU-2035; LYS-3326 AND GLY-3402.
RX   PubMed=20583297; DOI=10.1002/humu.21278;
RA   Clarke N.F., Waddell L.B., Cooper S.T., Perry M., Smith R.L.L.,
RA   Kornberg A.J., Muntoni F., Lillis S., Straub V., Bushby K.,
RA   Guglieri M., King M.D., Farrell M.A., Marty I., Lunardi J.,
RA   Monnier N., North K.N.;
RT   "Recessive mutations in RYR1 are a common cause of congenital fiber
RT   type disproportion.";
RL   Hum. Mutat. 31:E1544-E1550(2010).
RN   [68]
RP   VARIANTS MHS1 ASN-1056; HIS-1127; ARG-1467; VAL-1571; GLN-2013;
RP   GLY-2400; GLY-2593; GLN-3410; TYR-3501 AND CYS-3933, AND VARIANTS
RP   LYS-899; CYS-2060; CYS-2248; TYR-2976 AND GLN-3360.
RX   PubMed=20681998; DOI=10.1111/j.1399-0004.2010.01493.x;
RA   Tammaro A., Di Martino A., Bracco A., Cozzolino S., Savoia G.,
RA   Andria B., Cannavo A., Spagnuolo M., Piluso G., Aurino S., Nigro V.;
RT   "Novel missense mutations and unexpected multiple changes of RYR1 gene
RT   in 75 malignant hyperthermia families.";
RL   Clin. Genet. 79:438-447(2011).
RN   [69]
RP   VARIANTS CCD GLY-160; GLN-2204; HIS-3366; CYS-3933 AND ASP-4743, AND
RP   VARIANTS LEU-1787; CYS-2060 AND ALA-4493.
RX   PubMed=21674524; DOI=10.1002/mus.22009;
RA   Duarte S.T., Oliveira J., Santos R., Pereira P., Barroso C.,
RA   Conceicao I., Evangelista T.;
RT   "Dominant and recessive RYR1 mutations in adults with core lesions and
RT   mild muscle symptoms.";
RL   Muscle Nerve 44:102-108(2011).
RN   [70]
RP   VARIANTS MHS1 HIS-1056; MET-2627 AND LEU-4234.
RX   PubMed=24013571; DOI=10.1097/ALN.0b013e3182a8a998;
RA   Kim J.H., Jarvik G.P., Browning B.L., Rajagopalan R., Gordon A.S.,
RA   Rieder M.J., Robertson P.D., Nickerson D.A., Fisher N.A.,
RA   Hopkins P.M.;
RT   "Exome sequencing reveals novel rare variants in the ryanodine
RT   receptor and calcium channel genes in malignant hyperthermia
RT   families.";
RL   Anesthesiology 119:1054-1065(2013).
RN   [71]
RP   VARIANTS MHS1 ALA-40; CYS-163; ARG-248; ARG-341; PRO-487; ALA-518;
RP   CYS-614; HIS-1043; HIS-2163; MET-2206; HIS-2248; HIS-2351; MET-2354;
RP   LEU-2358; GLN-2383; ARG-2434; HIS-2454; ARG-3711; VAL-4178; ARG-4230;
RP   GLU-4837; HIS-4861 AND GLY-4906, VARIANTS CCD TRP-975; MET-2168 AND
RP   GLY-3238, AND VARIANTS MET-974; LEU-1109; ARG-1393; LEU-1787; CYS-2060
RP   AND VAL-2321.
RX   PubMed=23558838; DOI=10.1213/ANE.0b013e31828a71ff;
RA   Brandom B.W., Bina S., Wong C.A., Wallace T., Visoiu M.,
RA   Isackson P.J., Vladutiu G.D., Sambuughin N., Muldoon S.M.;
RT   "Ryanodine receptor type 1 gene variants in the malignant
RT   hyperthermia-susceptible population of the United States.";
RL   Anesth. Analg. 116:1078-1086(2013).
RN   [72]
RP   VARIANTS CCD HIS-4861; ALA-4897 AND THR-4898.
RX   PubMed=24561095; DOI=10.1016/j.neulet.2014.02.015;
RA   Gu M., Zhang S., Hu J., Yuan Y., Wang Z., Da Y., Wu S.;
RT   "Novel RYR1 missense mutations in six Chinese patients with central
RT   core disease.";
RL   Neurosci. Lett. 566:32-35(2014).
RN   [73]
RP   CHARACTERIZATION OF VARIANT MHS1 CYS-2508, CHARACTERIZATION OF VARIANT
RP   CCD GLY-2508, AND MUTAGENESIS OF ARG-2508.
RX   PubMed=26381711; DOI=10.1213/ANE.0000000000000886;
RA   Miyoshi H., Yasuda T., Otsuki S., Kondo T., Haraki T., Mukaida K.,
RA   Nakamura R., Hamada H., Kawamoto M.;
RT   "Several ryanodine receptor type 1 gene mutations of p.Arg2508 are
RT   potential sources of malignant hyperthermia.";
RL   Anesth. Analg. 121:994-1000(2015).
RN   [74]
RP   CHARACTERIZATION OF VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-248;
RP   ARG-341; CYS-401; HIS-401; SER-522; CYS-614 AND LEU-614, AND
RP   MUTAGENESIS OF TYR-522.
RX   PubMed=26115329; DOI=10.1371/journal.pone.0130606;
RA   Murayama T., Kurebayashi N., Yamazawa T., Oyamada H., Suzuki J.,
RA   Kanemaru K., Oguchi K., Iino M., Sakurai T.;
RT   "Divergent activity profiles of type 1 ryanodine receptor channels
RT   carrying malignant hyperthermia and central core disease mutations in
RT   the amino-terminal Region.";
RL   PLoS ONE 10:E0130606-E0130606(2015).
RN   [75]
RP   CHARACTERIZATION OF VARIANTS MHS1 CYS-2163; HIS-2163; MET-2168;
RP   MET-2206; THR-2350; ARG-2434; HIS-2435; CYS-2454; HIS-2454; CYS-2458;
RP   HIS-2458 AND HIS-2508, CHARACTERIZATION OF VARIANT CCD CYS-2508, AND
RP   CHARACTERIZATION OF VARIANT ALA-2375 AND HIS-2508.
RX   PubMed=27586648; DOI=10.1002/humu.23072;
RA   Murayama T., Kurebayashi N., Ogawa H., Yamazawa T., Oyamada H.,
RA   Suzuki J., Kanemaru K., Oguchi K., Iino M., Sakurai T.;
RT   "Genotype-phenotype correlations of malignant hyperthermia and central
RT   core disease mutations in the central region of the RYR1 channel.";
RL   Hum. Mutat. 37:1231-1241(2016).
RN   [76]
RP   VARIANT MHS1 TRP-4737, AND CHARACTERIZATION OF VARIANT MHS1 TRP-4737.
RX   PubMed=26631338; DOI=10.1016/j.nmd.2015.11.001;
RA   Johannsen S., Treves S., Mueller C.R., Moegele S., Schneiderbanger D.,
RA   Roewer N., Schuster F.;
RT   "Functional characterization of the RYR1 mutation p.Arg4737Trp
RT   associated with susceptibility to malignant hyperthermia.";
RL   Neuromuscul. Disord. 26:21-25(2016).
RN   [77]
RP   VARIANT ARG-705.
RX   PubMed=27616680; DOI=10.1002/pd.4925;
RA   Casey J., Flood K., Ennis S., Doyle E., Farrell M., Lynch S.A.;
RT   "Intra-familial variability associated with recessive RYR1 mutation
RT   diagnosed prenatally by exome sequencing.";
RL   Prenat. Diagn. 36:1020-1026(2016).
RN   [78]
RP   VARIANTS CCD PRO-2963 AND ASP-4806.
RX   PubMed=27234031; DOI=10.1111/cge.12810;
RA   Fattahi Z., Kalhor Z., Fadaee M., Vazehan R., Parsimehr E.,
RA   Abolhassani A., Beheshtian M., Zamani G., Nafissi S., Nilipour Y.,
RA   Akbari M.R., Kahrizi K., Kariminejad A., Najmabadi H.;
RT   "Improved diagnostic yield of neuromuscular disorders applying
RT   clinical exome sequencing in patients arising from a consanguineous
RT   population.";
RL   Clin. Genet. 91:386-402(2017).
CC   -!- FUNCTION: Calcium channel that mediates the release of Ca(2+) from
CC       the sarcoplasmic reticulum into the cytoplasm and thereby plays a
CC       key role in triggering muscle contraction following depolarization
CC       of T-tubules (PubMed:11741831, PubMed:16163667). Repeated very
CC       high-level exercise increases the open probability of the channel
CC       and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335).
CC       Can also mediate the release of Ca(2+) from intracellular stores
CC       in neurons, and may thereby promote prolonged Ca(2+) signaling in
CC       the brain. Required for normal embryonic development of muscle
CC       fibers and skeletal muscle. Required for normal heart
CC       morphogenesis, skin development and ossification during
CC       embryogenesis (By similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC       ECO:0000269|PubMed:18268335, ECO:0000305|PubMed:11741831,
CC       ECO:0000305|PubMed:16163667}.
CC   -!- ENZYME REGULATION: Channel activity is modulated by the alkaloid
CC       ryanodine that binds to the open Ca-release channel with high
CC       affinity. At low concentrations, ryanodine maintains the channel
CC       in an open conformation. High ryanodine concentrations inhibit
CC       channel activity (By similarity). Channel activity is regulated by
CC       calmodulin (CALM) (PubMed:18650434). The calcium release is
CC       activated by increased cytoplasmic calcium levels, by nitric oxyde
CC       (NO), caffeine and ATP (PubMed:18268335, PubMed:16163667). Channel
CC       activity is inhibited by magnesium ions, possibly by competition
CC       for calcium binding sites (By similarity).
CC       {ECO:0000250|UniProtKB:P11716, ECO:0000269|PubMed:16163667,
CC       ECO:0000269|PubMed:18268335, ECO:0000269|PubMed:18650434}.
CC   -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR2 (By
CC       similarity). Identified in a complex composed of RYR1, PDE4D, PKA,
CC       FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). Repeated
CC       very high-level exercise decreases interaction with PDE4D and
CC       protein phosphatase 1 (PP1) (PubMed:18268335). Interacts with
CC       CALM; CALM with bound calcium inhibits the RYR1 channel activity
CC       (PubMed:18650434). Interacts with S100A1 (PubMed:18650434).
CC       Interacts with FKBP1A; this stabilizes the closed conformation of
CC       the channel. Interacts with CACNA1S; interaction with CACNA1S is
CC       important for activation of the RYR1 channel. Interacts with
CC       CACNB1. Interacts with TRDN and ASPH; these interactions stimulate
CC       RYR1 channel activity. Interacts with SELENON (By similarity).
CC       {ECO:0000250|UniProtKB:E9PZQ0, ECO:0000250|UniProtKB:P11716,
CC       ECO:0000269|PubMed:18268335, ECO:0000269|PubMed:18650434}.
CC   -!- INTERACTION:
CC       P54296:MYOM2; NbExp=2; IntAct=EBI-1221290, EBI-5357134;
CC   -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:7556644}; Multi-pass membrane protein
CC       {ECO:0000305}. Sarcoplasmic reticulum
CC       {ECO:0000250|UniProtKB:P11716}. Note=The number of predicted
CC       transmembrane domains varies between orthologs, but the 3D-
CC       structures show the presence of six transmembrane regions. Both N-
CC       terminus and C-terminus are cytoplasmic.
CC       {ECO:0000250|UniProtKB:P11716}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC         Comment=Experimental confirmation may be lacking for some
CC         isoforms.;
CC       Name=1;
CC         IsoId=P21817-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P21817-2; Sequence=VSP_005951;
CC       Name=3;
CC         IsoId=P21817-3; Sequence=VSP_005952;
CC   -!- TISSUE SPECIFICITY: Skeletal muscle and brain (cerebellum and
CC       hippocampus). {ECO:0000269|PubMed:9607712}.
CC   -!- DOMAIN: The calcium release channel activity resides in the C-
CC       terminal region while the remaining part of the protein
CC       constitutes the 'foot' structure spanning the junctional gap
CC       between the sarcoplasmic reticulum (SR) and the T-tubule. Pore
CC       opening is mediated via the cytoplasmic calcium-binding domains
CC       that mediate a small rotation of the channel-forming transmembrane
CC       regions that then leads to channel opening.
CC       {ECO:0000250|UniProtKB:P11716}.
CC   -!- PTM: Channel activity is modulated by phosphorylation.
CC       Phosphorylation at Ser-2843 may increase channel activity.
CC       Repeated very high-level exercise increases phosphorylation at
CC       Ser-2843. {ECO:0000269|PubMed:18268335}.
CC   -!- PTM: Activated by reversible S-nitrosylation (By similarity).
CC       Repeated very high-level exercise increases S-nitrosylation
CC       (PubMed:18268335). {ECO:0000250|UniProtKB:P11716,
CC       ECO:0000269|PubMed:18268335}.
CC   -!- DISEASE: Malignant hyperthermia 1 (MHS1) [MIM:145600]: Autosomal
CC       dominant pharmacogenetic disorder of skeletal muscle and is one of
CC       the main causes of death due to anesthesia. In susceptible people,
CC       an MH episode can be triggered by all commonly used inhalational
CC       anesthetics such as halothane and by depolarizing muscle relaxants
CC       such as succinylcholine. The clinical features of the myopathy are
CC       hyperthermia, accelerated muscle metabolism, contractures,
CC       metabolic acidosis, tachycardia and death, if not treated with the
CC       postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can
CC       be determined with the 'in vitro' contracture test (IVCT):
CC       observing the magnitude of contractures induced in strips of
CC       muscle tissue by caffeine alone and halothane alone. Patients with
CC       normal response are MH normal (MHN), those with abnormal response
CC       to caffeine alone or halothane alone are MH equivocal (MHE(C) and
CC       MHE(H) respectively). {ECO:0000269|PubMed:10051009,
CC       ECO:0000269|PubMed:10484775, ECO:0000269|PubMed:10612851,
CC       ECO:0000269|PubMed:10823104, ECO:0000269|PubMed:10888602,
CC       ECO:0000269|PubMed:11241852, ECO:0000269|PubMed:11389482,
CC       ECO:0000269|PubMed:11525881, ECO:0000269|PubMed:11575529,
CC       ECO:0000269|PubMed:11928716, ECO:0000269|PubMed:12059893,
CC       ECO:0000269|PubMed:12066726, ECO:0000269|PubMed:12123492,
CC       ECO:0000269|PubMed:12208234, ECO:0000269|PubMed:12411788,
CC       ECO:0000269|PubMed:12709367, ECO:0000269|PubMed:12883402,
CC       ECO:0000269|PubMed:1354642, ECO:0000269|PubMed:14732627,
CC       ECO:0000269|PubMed:14985404, ECO:0000269|PubMed:15221887,
CC       ECO:0000269|PubMed:15448513, ECO:0000269|PubMed:16163667,
CC       ECO:0000269|PubMed:1774074, ECO:0000269|PubMed:19191329,
CC       ECO:0000269|PubMed:19685112, ECO:0000269|PubMed:20142353,
CC       ECO:0000269|PubMed:20681998, ECO:0000269|PubMed:23558838,
CC       ECO:0000269|PubMed:24013571, ECO:0000269|PubMed:26115329,
CC       ECO:0000269|PubMed:26381711, ECO:0000269|PubMed:26631338,
CC       ECO:0000269|PubMed:27586648, ECO:0000269|PubMed:7751854,
CC       ECO:0000269|PubMed:7849712, ECO:0000269|PubMed:7881417,
CC       ECO:0000269|PubMed:8012359, ECO:0000269|PubMed:8220423,
CC       ECO:0000269|PubMed:9066328, ECO:0000269|PubMed:9138151,
CC       ECO:0000269|PubMed:9389851, ECO:0000269|PubMed:9450902,
CC       ECO:0000269|PubMed:9497245}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Central core disease of muscle (CCD) [MIM:117000]:
CC       Autosomal dominant congenital myopathy, but a severe autosomal
CC       recessive form also exists. Both clinical and histological
CC       variability is observed. Affected individuals typically display
CC       hypotonia and proximal muscle weakness in infancy, leading to the
CC       delay of motor milestones. The clinical course of the disorder is
CC       usually slow or nonprogressive in adulthood, and the severity of
CC       the symptoms may vary from normal to significant muscle weakness.
CC       Microscopic examination of CCD-affected skeletal muscle reveals a
CC       predominance of type I fibers containing amorphous-looking areas
CC       (cores) that do not stain with oxidative and phosphorylase
CC       histochemical techniques. {ECO:0000269|PubMed:10097181,
CC       ECO:0000269|PubMed:11113224, ECO:0000269|PubMed:11709545,
CC       ECO:0000269|PubMed:11741831, ECO:0000269|PubMed:12112081,
CC       ECO:0000269|PubMed:12136074, ECO:0000269|PubMed:12565913,
CC       ECO:0000269|PubMed:12566385, ECO:0000269|PubMed:12937085,
CC       ECO:0000269|PubMed:14670767, ECO:0000269|PubMed:14985404,
CC       ECO:0000269|PubMed:17204054, ECO:0000269|PubMed:17226826,
CC       ECO:0000269|PubMed:18253926, ECO:0000269|PubMed:18312400,
CC       ECO:0000269|PubMed:20142353, ECO:0000269|PubMed:21674524,
CC       ECO:0000269|PubMed:23558838, ECO:0000269|PubMed:24561095,
CC       ECO:0000269|PubMed:26381711, ECO:0000269|PubMed:27234031,
CC       ECO:0000269|PubMed:27586648, ECO:0000269|PubMed:7829078,
CC       ECO:0000269|PubMed:8220422, ECO:0000269|PubMed:8220423,
CC       ECO:0000269|PubMed:9497245}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Multiminicore disease with external ophthalmoplegia
CC       (MMDO) [MIM:255320]: Clinically heterogeneous neuromuscular
CC       disorder. General features include neonatal hypotonia, delayed
CC       motor development, and generalized muscle weakness and amyotrophy,
CC       which may progress slowly or remain stable. Muscle biopsy shows
CC       multiple, poorly circumscribed, short areas of sarcomere
CC       disorganization and mitochondria depletion (areas termed
CC       minicores) in most muscle fibers. Typically, no dystrophic signs,
CC       such as muscle fiber necrosis or regeneration or significant
CC       endomysial fibrosis, are present in multiminicore disease.
CC       {ECO:0000269|PubMed:12719381, ECO:0000269|PubMed:16380615,
CC       ECO:0000269|PubMed:20583297}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Note=Defects in RYR1 may be a cause of Samaritan
CC       myopathy, a congenital myopathy with benign course. Patients
CC       display severe hypotonia and respiratory distress at birth. Unlike
CC       other congenital myopathies, the health status constantly improves
CC       and patients are minimally affected at adulthood.
CC   -!- MISCELLANEOUS: Coexpression of normal and mutant Thr-4898 RYR1 in
CC       a 1:1 ratio produces RYR1 channels with normal halothane and
CC       caffeine sensitivities, but maximal levels of Ca(2+) release are
CC       reduced by 67%. Binding of [3H]ryanodine indicates that the
CC       heterozygous channel is activated by Ca(2+) concentrations 4-fold
CC       lower than normal. Single-cell analysis of cotransfected cells
CC       shows a significantly increased resting cytoplasmic Ca(2+) level
CC       and a significantly reduced luminal Ca(2+) level. These data
CC       indicated a leaky channel, possibly caused by a reduction in the
CC       Ca(2+) concentration required for channel activation. Comparison
CC       with 2 other coexpressed mutant/normal channels suggests that the
CC       Thr-4898 mutation produces one of the most abnormal RYR1 channels
CC       that has been investigated, and this level of abnormality is
CC       reflected in the severe and penetrant phenotype of affected CCD
CC       individuals. {ECO:0000269|PubMed:10097181}.
CC   -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family.
CC       RYR1 subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Ryanodine receptor entry;
CC       URL="https://en.wikipedia.org/wiki/Ryanodine_receptor";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=RYR1 entry;
CC       URL="https://en.wikipedia.org/wiki/RYR1";
CC   -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages Ryanodine
CC       receptor 1 (skeletal) (RYR1); Note=Leiden Open Variation Database
CC       (LOVD);
CC       URL="http://www.dmd.nl/nmdb2/home.php?select_db=RYR1";
DR   EMBL; J05200; AAA60294.1; -; mRNA.
DR   EMBL; U48508; AAC51191.1; -; Genomic_DNA.
DR   EMBL; U48449; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48450; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48451; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48452; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48453; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48454; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48455; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48456; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48457; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48458; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48459; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48460; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48461; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48462; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48463; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48464; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48465; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48466; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48467; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48468; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48469; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48470; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48471; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48472; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48473; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48474; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48475; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48476; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48477; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48478; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48479; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48480; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48481; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48482; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48483; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48484; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48485; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48486; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48487; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48488; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48489; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48490; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48491; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48492; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48493; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48494; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48495; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48496; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48497; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48498; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48499; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48500; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48501; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48502; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48503; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48504; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48505; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48506; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; U48507; AAC51191.1; JOINED; Genomic_DNA.
DR   EMBL; AC067969; AAF66076.1; -; Genomic_DNA.
DR   EMBL; AC005933; AAC71651.1; -; Genomic_DNA.
DR   EMBL; AC011469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; M91455; AAA60295.1; -; Genomic_DNA.
DR   EMBL; S78717; AAB21245.2; -; Genomic_DNA.
DR   EMBL; S77392; AAB34356.1; -; Genomic_DNA.
DR   CCDS; CCDS33011.1; -. [P21817-1]
DR   CCDS; CCDS42563.1; -. [P21817-2]
DR   PIR; A35041; A35041.
DR   RefSeq; NP_000531.2; NM_000540.2. [P21817-1]
DR   RefSeq; NP_001036188.1; NM_001042723.1. [P21817-2]
DR   UniGene; Hs.466664; -.
DR   ProteinModelPortal; P21817; -.
DR   BioGrid; 112173; 8.
DR   DIP; DIP-29708N; -.
DR   ELM; P21817; -.
DR   IntAct; P21817; 10.
DR   MINT; MINT-1605046; -.
DR   STRING; 9606.ENSP00000352608; -.
DR   BindingDB; P21817; -.
DR   ChEMBL; CHEMBL1846; -.
DR   DrugBank; DB00201; Caffeine.
DR   DrugBank; DB01219; Dantrolene.
DR   DrugBank; DB04786; Suramin.
DR   DrugBank; DB09085; Tetracaine.
DR   GuidetoPHARMACOLOGY; 747; -.
DR   TCDB; 1.A.3.1.2; the ryanodine-inositol 1,4,5-triphosphate receptor ca(2+) channel (rir-cac) family.
DR   iPTMnet; P21817; -.
DR   PhosphoSitePlus; P21817; -.
DR   BioMuta; RYR1; -.
DR   DMDM; 108935904; -.
DR   PaxDb; P21817; -.
DR   PeptideAtlas; P21817; -.
DR   PRIDE; P21817; -.
DR   Ensembl; ENST00000355481; ENSP00000347667; ENSG00000196218. [P21817-2]
DR   Ensembl; ENST00000359596; ENSP00000352608; ENSG00000196218. [P21817-1]
DR   GeneID; 6261; -.
DR   KEGG; hsa:6261; -.
DR   UCSC; uc002oit.4; human. [P21817-1]
DR   CTD; 6261; -.
DR   DisGeNET; 6261; -.
DR   GeneCards; RYR1; -.
DR   GeneReviews; RYR1; -.
DR   H-InvDB; HIX0039957; -.
DR   HGNC; HGNC:10483; RYR1.
DR   HPA; HPA056416; -.
DR   MalaCards; RYR1; -.
DR   MIM; 117000; phenotype.
DR   MIM; 145600; phenotype.
DR   MIM; 180901; gene.
DR   MIM; 255320; phenotype.
DR   neXtProt; NX_P21817; -.
DR   OpenTargets; ENSG00000196218; -.
DR   Orphanet; 169189; Autosomal dominant centronuclear myopathy.
DR   Orphanet; 324581; Benign Samaritan congenital myopathy.
DR   Orphanet; 597; Central core disease.
DR   Orphanet; 98905; Congenital multicore myopathy with external ophthalmoplegia.
DR   Orphanet; 99741; King-Denborough syndrome.
DR   Orphanet; 423; Malignant hyperthermia.
DR   Orphanet; 178145; Moderate multiminicore disease with hand involvement.
DR   PharmGKB; PA34896; -.
DR   eggNOG; KOG2243; Eukaryota.
DR   eggNOG; ENOG410YCNW; LUCA.
DR   GeneTree; ENSGT00760000119152; -.
DR   HOGENOM; HOG000231428; -.
DR   HOVERGEN; HBG006699; -.
DR   InParanoid; P21817; -.
DR   KO; K04961; -.
DR   OMA; DIPARRN; -.
DR   OrthoDB; EOG091G00T0; -.
DR   PhylomeDB; P21817; -.
DR   TreeFam; TF315244; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   Reactome; R-HSA-5578775; Ion homeostasis.
DR   SIGNOR; P21817; -.
DR   ChiTaRS; RYR1; human.
DR   GeneWiki; RYR1; -.
DR   GenomeRNAi; 6261; -.
DR   PRO; PR:P21817; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000196218; -.
DR   CleanEx; HS_RYR1; -.
DR   ExpressionAtlas; P21817; baseline and differential.
DR   Genevisible; P21817; HS.
DR   GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0031674; C:I band; IDA:UniProtKB.
DR   GO; GO:0031301; C:integral component of organelle membrane; ISS:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0030314; C:junctional membrane complex; IEA:Ensembl.
DR   GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; TAS:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:1990425; C:ryanodine receptor complex; ISS:UniProtKB.
DR   GO; GO:0016529; C:sarcoplasmic reticulum; ISS:BHF-UCL.
DR   GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0005790; C:smooth endoplasmic reticulum; TAS:ProtInc.
DR   GO; GO:0030315; C:T-tubule; IEA:Ensembl.
DR   GO; GO:0014802; C:terminal cisterna; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR   GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0048763; F:calcium-induced calcium release activity; IMP:UniProtKB.
DR   GO; GO:0015278; F:calcium-release channel activity; TAS:ProtInc.
DR   GO; GO:0005516; F:calmodulin binding; ISS:BHF-UCL.
DR   GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR   GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IDA:CACAO.
DR   GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR   GO; GO:0006816; P:calcium ion transport; ISS:BHF-UCL.
DR   GO; GO:0071313; P:cellular response to caffeine; IMP:UniProtKB.
DR   GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR   GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0006936; P:muscle contraction; ISS:UniProtKB.
DR   GO; GO:0043931; P:ossification involved in bone maturation; ISS:UniProtKB.
DR   GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
DR   GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR   GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR   GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR   GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR   GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0031000; P:response to caffeine; ISS:BHF-UCL.
DR   GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
DR   GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR   GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR   InterPro; IPR001870; B30.2/SPRY.
DR   InterPro; IPR013320; ConA-like_dom.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR014821; Ins145_P3_rcpt.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR016093; MIR_motif.
DR   InterPro; IPR013662; RIH_assoc-dom.
DR   InterPro; IPR000699; RIH_dom.
DR   InterPro; IPR013333; Ryan_recept.
DR   InterPro; IPR003032; Ryanodine_rcpt.
DR   InterPro; IPR015925; Ryanodine_recept-rel.
DR   InterPro; IPR009460; Ryanrecept_TM4-6.
DR   InterPro; IPR033215; RyR1.
DR   InterPro; IPR003877; SPRY_dom.
DR   PANTHER; PTHR13715; PTHR13715; 1.
DR   PANTHER; PTHR13715:SF97; PTHR13715:SF97; 1.
DR   Pfam; PF13833; EF-hand_8; 1.
DR   Pfam; PF08709; Ins145_P3_rec; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF02815; MIR; 1.
DR   Pfam; PF08454; RIH_assoc; 1.
DR   Pfam; PF06459; RR_TM4-6; 1.
DR   Pfam; PF01365; RYDR_ITPR; 2.
DR   Pfam; PF02026; RyR; 4.
DR   Pfam; PF00622; SPRY; 3.
DR   PRINTS; PR00795; RYANODINER.
DR   SMART; SM00472; MIR; 4.
DR   SMART; SM00449; SPRY; 3.
DR   SUPFAM; SSF100909; SSF100909; 2.
DR   SUPFAM; SSF47473; SSF47473; 1.
DR   SUPFAM; SSF49899; SSF49899; 2.
DR   SUPFAM; SSF82109; SSF82109; 2.
DR   PROSITE; PS50188; B302_SPRY; 3.
DR   PROSITE; PS50919; MIR; 5.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Calcium; Calcium channel;
KW   Calcium transport; Calmodulin-binding; Complete proteome;
KW   Developmental protein; Direct protein sequencing; Disease mutation;
KW   Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW   Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW   Receptor; Reference proteome; Repeat; S-nitrosylation;
KW   Sarcoplasmic reticulum; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN         1   5038       Ryanodine receptor 1.
FT                                /FTId=PRO_0000219358.
FT   TOPO_DOM      1   4559       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TRANSMEM   4560   4580       Helical; Name=1.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4581   4641       Lumenal. {ECO:0000250|UniProtKB:P11716}.
FT   TRANSMEM   4642   4662       Helical; Name=2.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4663   4780       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TRANSMEM   4781   4803       Helical; Name=3.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4804   4804       Lumenal. {ECO:0000250|UniProtKB:P11716}.
FT   TRANSMEM   4805   4821       Helical; Name=4.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4822   4836       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TRANSMEM   4837   4857       Helical; Name=5.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4858   4880       Lumenal. {ECO:0000250|UniProtKB:P11716}.
FT   INTRAMEM   4881   4900       Pore-forming.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4901   4920       Lumenal. {ECO:0000250|UniProtKB:P11716}.
FT   TRANSMEM   4921   4941       Helical; Name=6.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   TOPO_DOM   4942   5038       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   DOMAIN       97    152       MIR 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      159    204       MIR 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      210    264       MIR 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      270    327       MIR 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      335    392       MIR 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00131}.
FT   DOMAIN      581    797       B30.2/SPRY 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00548}.
FT   REPEAT      841    954       1.
FT   REPEAT      955   1068       2.
FT   DOMAIN     1013   1208       B30.2/SPRY 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00548}.
FT   REPEAT     1344   1359       3; truncated.
FT   DOMAIN     1356   1570       B30.2/SPRY 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00548}.
FT   REPEAT     1372   1387       4; truncated.
FT   REPEAT     2726   2845       5.
FT   REPEAT     2846   2959       6.
FT   DOMAIN     4074   4102       EF-hand. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00448}.
FT   NP_BIND    4210   4214       ATP. {ECO:0000250|UniProtKB:P11716}.
FT   NP_BIND    4955   4960       ATP. {ECO:0000250|UniProtKB:P11716}.
FT   NP_BIND    4980   4986       ATP. {ECO:0000250|UniProtKB:P11716}.
FT   REGION      669    680       Interaction with FKBP1A.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   REGION      841   2959       6 X approximate repeats.
FT   REGION     3614   3643       Interaction with CALM.
FT                                {ECO:0000269|PubMed:18650434}.
FT   MOTIF      4895   4901       Selectivity filter.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   COMPBIAS   1873   1924       Glu-rich (acidic).
FT   COMPBIAS   4462   4532       Pro-rich.
FT   METAL      3892   3892       Calcium. {ECO:0000250|UniProtKB:P11716}.
FT   METAL      3966   3966       Calcium. {ECO:0000250|UniProtKB:P11716}.
FT   METAL      5002   5002       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   BINDING    4717   4717       Caffeine. {ECO:0000250|UniProtKB:P11716}.
FT   MOD_RES    1337   1337       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:F1LMY4}.
FT   MOD_RES    2345   2345       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:F1LMY4}.
FT   MOD_RES    2843   2843       Phosphoserine; by PKA and PKG.
FT                                {ECO:0000250|UniProtKB:E9PZQ0}.
FT   MOD_RES    3635   3635       S-nitrosocysteine.
FT                                {ECO:0000250|UniProtKB:P11716}.
FT   MOD_RES    4467   4467       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:F1LMY4}.
FT   MOD_RES    4471   4471       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:F1LMY4}.
FT   MOD_RES    4864   4864       Phosphotyrosine.
FT                                {ECO:0000244|PubMed:18318008}.
FT   MOD_RES    4867   4867       Phosphoserine.
FT                                {ECO:0000244|PubMed:18318008}.
FT   VAR_SEQ    3481   3485       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:2298749}.
FT                                /FTId=VSP_005951.
FT   VAR_SEQ    3865   3869       Missing (in isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_005952.
FT   VARIANT      13     13       L -> R (in MHS1; dbSNP:rs193922744).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058560.
FT   VARIANT      13     13       L -> V (in CCD; autosomal recessive
FT                                form). {ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045694.
FT   VARIANT      35     35       C -> R (in MHS1; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs193922747).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:26115329,
FT                                ECO:0000269|PubMed:9066328}.
FT                                /FTId=VAR_005589.
FT   VARIANT      40     40       G -> A (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071721.
FT   VARIANT      44     44       R -> C (in CCD and MHS1;
FT                                dbSNP:rs193922748).
FT                                {ECO:0000269|PubMed:12709367}.
FT                                /FTId=VAR_045695.
FT   VARIANT     109    109       R -> W (in MMDO; dbSNP:rs118192173).
FT                                {ECO:0000269|PubMed:16380615}.
FT                                /FTId=VAR_032910.
FT   VARIANT     160    160       E -> G (in CCD; dbSNP:rs193922752).
FT                                {ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:21674524}.
FT                                /FTId=VAR_045696.
FT   VARIANT     163    163       R -> C (in CCD and MHS1; 2-3% of the
FT                                cases; increases calcium-induced calcium
FT                                release activity; dbSNP:rs118192161).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:12411788,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:26115329,
FT                                ECO:0000269|PubMed:8220423}.
FT                                /FTId=VAR_005590.
FT   VARIANT     163    163       R -> L (in MHS1; induces an increase
FT                                sensitivity to caffeine; increases
FT                                calcium-induced calcium release activity;
FT                                dbSNP:rs193922753).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:26115329}.
FT                                /FTId=VAR_045697.
FT   VARIANT     165    165       G -> R (in MHS1; dbSNP:rs193922754).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045698.
FT   VARIANT     166    166       D -> N (in MHS1; dbSNP:rs193922755).
FT                                {ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045699.
FT   VARIANT     177    177       R -> C (in MHS1; dbSNP:rs193922757).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045700.
FT   VARIANT     178    178       Y -> C (in MHS1).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045701.
FT   VARIANT     215    215       G -> E (in CCD; autosomal recessive form;
FT                                dbSNP:rs118192115).
FT                                {ECO:0000269|PubMed:12937085}.
FT                                /FTId=VAR_045702.
FT   VARIANT     226    226       M -> K (in MHS1; dbSNP:rs112596687).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058561.
FT   VARIANT     227    227       D -> V (in MHS1; dbSNP:rs193922760).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045703.
FT   VARIANT     248    248       G -> R (in MHS1; unknown pathological
FT                                significance; increases calcium-induced
FT                                calcium release activity;
FT                                dbSNP:rs1801086).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:1354642,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:26115329}.
FT                                /FTId=VAR_005591.
FT   VARIANT     291    291       A -> T (in dbSNP:rs2229140).
FT                                /FTId=VAR_051890.
FT   VARIANT     328    328       R -> W (in MHS1; has increased
FT                                sensitivity to both caffeine and
FT                                halothane; dbSNP:rs193922762).
FT                                {ECO:0000269|PubMed:12883402,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045704.
FT   VARIANT     341    341       G -> R (in MHS1; 10% of the cases;
FT                                increases calcium-induced calcium release
FT                                activity; dbSNP:rs28933997).
FT                                {ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12411788,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:26115329,
FT                                ECO:0000269|PubMed:8012359}.
FT                                /FTId=VAR_005592.
FT   VARIANT     367    367       R -> L (in MHS1; dbSNP:rs113332073).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058562.
FT   VARIANT     382    382       H -> N (in MHS1).
FT                                {ECO:0000269|PubMed:20142353}.
FT                                /FTId=VAR_068510.
FT   VARIANT     401    401       R -> C (in MHS1; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs193922764).
FT                                {ECO:0000269|PubMed:12066726,
FT                                ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:26115329}.
FT                                /FTId=VAR_045705.
FT   VARIANT     401    401       R -> H (in MHS1; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs193922766).
FT                                {ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:26115329}.
FT                                /FTId=VAR_045706.
FT   VARIANT     401    401       R -> S (in MHS1).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045707.
FT   VARIANT     402    402       M -> T (in MMDO; dbSNP:rs118192117).
FT                                {ECO:0000269|PubMed:20583297}.
FT                                /FTId=VAR_063846.
FT   VARIANT     403    403       I -> M (in CCD and MHS1;
FT                                dbSNP:rs118192116).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:8220423}.
FT                                /FTId=VAR_005593.
FT   VARIANT     471    471       R -> C. {ECO:0000269|PubMed:1354642}.
FT                                /FTId=VAR_005594.
FT   VARIANT     485    485       M -> V (in dbSNP:rs147723844).
FT                                {ECO:0000269|PubMed:16380615}.
FT                                /FTId=VAR_032911.
FT   VARIANT     487    487       L -> P (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071722.
FT   VARIANT     518    518       V -> A (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071723.
FT   VARIANT     522    522       Y -> S (in CCD and MHS1; increases
FT                                calcium-induced calcium release activity;
FT                                dbSNP:rs118192162).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:26115329,
FT                                ECO:0000269|PubMed:7829078}.
FT                                /FTId=VAR_005595.
FT   VARIANT     530    530       R -> H (in MHS1; dbSNP:rs111888148).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058563.
FT   VARIANT     533    533       R -> C (in MHS1; dbSNP:rs193922768).
FT                                {ECO:0000269|PubMed:12709367}.
FT                                /FTId=VAR_045708.
FT   VARIANT     533    533       R -> H (in MHS1; dbSNP:rs144336148).
FT                                /FTId=VAR_008971.
FT   VARIANT     544    544       D -> Y (in MHS1; dbSNP:rs113812662).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058564.
FT   VARIANT     552    552       R -> W (in MHS1; dbSNP:rs193922770).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:9138151}.
FT                                /FTId=VAR_005596.
FT   VARIANT     614    614       R -> C (in CCD and MHS1; 3-5% of the
FT                                cases; increases calcium-induced calcium
FT                                release activity; dbSNP:rs28933996).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12411788,
FT                                ECO:0000269|PubMed:12937085,
FT                                ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:1774074,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:26115329,
FT                                ECO:0000269|PubMed:7751854}.
FT                                /FTId=VAR_005597.
FT   VARIANT     614    614       R -> L (in MHS1; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs193922772).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:26115329,
FT                                ECO:0000269|PubMed:9389851}.
FT                                /FTId=VAR_005598.
FT   VARIANT     705    705       G -> R (probable disease-associated
FT                                mutation found in primary myopathy
FT                                causing fetal akinesia and pregnancy
FT                                loss; dbSNP:rs565825739).
FT                                {ECO:0000269|PubMed:27616680}.
FT                                /FTId=VAR_078775.
FT   VARIANT     899    899       N -> K (in dbSNP:rs201401814).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071724.
FT   VARIANT     974    974       V -> M (in dbSNP:rs748676912).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071725.
FT   VARIANT     975    975       R -> W (in CCD; unknown pathological
FT                                significance; dbSNP:rs371278145).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071726.
FT   VARIANT    1043   1043       R -> C (in MHS1; dbSNP:rs111272095).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058565.
FT   VARIANT    1043   1043       R -> H (in MHS1; unknown pathological
FT                                significance; dbSNP:rs374776563).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071727.
FT   VARIANT    1056   1056       D -> H (in MHS1).
FT                                {ECO:0000269|PubMed:24013571}.
FT                                /FTId=VAR_071728.
FT   VARIANT    1056   1056       D -> N (in MHS1).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071729.
FT   VARIANT    1058   1058       E -> K (in MHS1).
FT                                {ECO:0000269|PubMed:20142353}.
FT                                /FTId=VAR_068511.
FT   VARIANT    1088   1088       Y -> C (probable disease-associated
FT                                mutation found in a family with Samaritan
FT                                myopathy). {ECO:0000269|PubMed:22752422}.
FT                                /FTId=VAR_068512.
FT   VARIANT    1109   1109       R -> K (in dbSNP:rs35719391).
FT                                /FTId=VAR_032912.
FT   VARIANT    1109   1109       R -> L. {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071730.
FT   VARIANT    1127   1127       R -> H (in MHS1; dbSNP:rs545579559).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071731.
FT   VARIANT    1342   1342       S -> G (in dbSNP:rs34694816).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_032913.
FT   VARIANT    1352   1352       A -> G (in MHS1; dbSNP:rs112105381).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058566.
FT   VARIANT    1393   1393       K -> R (in MHS1; unknown pathological
FT                                significance; dbSNP:rs137933390).
FT                                {ECO:0000269|PubMed:20142353,
FT                                ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_068513.
FT   VARIANT    1467   1467       K -> R (in MHS1; dbSNP:rs145573319).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071732.
FT   VARIANT    1489   1489       S -> N (in dbSNP:rs34404839).
FT                                /FTId=VAR_032914.
FT   VARIANT    1571   1571       I -> V (in MHS1; dbSNP:rs146429605).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071733.
FT   VARIANT    1679   1679       R -> H (may be associated with
FT                                susceptibility to malignant hyperthermia;
FT                                dbSNP:rs146504767).
FT                                {ECO:0000269|PubMed:20142353}.
FT                                /FTId=VAR_068514.
FT   VARIANT    1704   1704       G -> S (in CCD; autosomal recessive form;
FT                                dbSNP:rs193922779).
FT                                {ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045709.
FT   VARIANT    1787   1787       P -> L (in MHS1; dbSNP:rs34934920).
FT                                {ECO:0000269|PubMed:1354642,
FT                                ECO:0000269|PubMed:19191329,
FT                                ECO:0000269|PubMed:21674524,
FT                                ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_005599.
FT   VARIANT    1832   1832       G -> A (in dbSNP:rs193922784).
FT                                {ECO:0000269|PubMed:11928716,
FT                                ECO:0000269|PubMed:19191329,
FT                                ECO:0000269|PubMed:8661021}.
FT                                /FTId=VAR_045710.
FT   VARIANT    2013   2013       K -> Q (in MHS1).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071734.
FT   VARIANT    2035   2035       H -> L (in MMDO; dbSNP:rs367543056).
FT                                {ECO:0000269|PubMed:20583297}.
FT                                /FTId=VAR_063847.
FT   VARIANT    2060   2060       G -> C (in MHS1; dbSNP:rs35364374).
FT                                {ECO:0000269|PubMed:1354642,
FT                                ECO:0000269|PubMed:16380615,
FT                                ECO:0000269|PubMed:19191329,
FT                                ECO:0000269|PubMed:20681998,
FT                                ECO:0000269|PubMed:21674524,
FT                                ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_005600.
FT   VARIANT    2101   2101       M -> K (in dbSNP:rs746818096).
FT                                {ECO:0000269|PubMed:12709367}.
FT                                /FTId=VAR_045711.
FT   VARIANT    2117   2117       V -> L (in MHS1; dbSNP:rs193922788).
FT                                {ECO:0000269|PubMed:12709367}.
FT                                /FTId=VAR_045712.
FT   VARIANT    2129   2129       D -> E (in MHS1; dbSNP:rs117886618).
FT                                {ECO:0000269|PubMed:11241852,
FT                                ECO:0000269|PubMed:12059893}.
FT                                /FTId=VAR_045713.
FT   VARIANT    2163   2163       R -> C (in MHS1; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs28933998).
FT                                {ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:9497245}.
FT                                /FTId=VAR_005601.
FT   VARIANT    2163   2163       R -> H (in CCD and MHS1; increases
FT                                calcium-induced calcium release activity;
FT                                dbSNP:rs28933999).
FT                                {ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:9497245}.
FT                                /FTId=VAR_005602.
FT   VARIANT    2163   2163       R -> P (in MHS1; dbSNP:rs118192163).
FT                                {ECO:0000269|PubMed:12709367}.
FT                                /FTId=VAR_008972.
FT   VARIANT    2168   2168       V -> M (in CCD and MHS1; no difference in
FT                                the thapsigargin-sensitive calcium stores
FT                                of cells carrying this mutation and the
FT                                wild-type; increases calcium-induced
FT                                calcium release activity;
FT                                dbSNP:rs118192176).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:11709545,
FT                                ECO:0000269|PubMed:11741831,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12709367,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:9497245}.
FT                                /FTId=VAR_005603.
FT   VARIANT    2204   2204       H -> Q (in CCD; dbSNP:rs141646642).
FT                                {ECO:0000269|PubMed:21674524}.
FT                                /FTId=VAR_068515.
FT   VARIANT    2206   2206       T -> M (in MHS1; induces an increase
FT                                sensitivity to caffeine;
FT                                dbSNP:rs28934000).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:9497245}.
FT                                /FTId=VAR_005604.
FT   VARIANT    2206   2206       T -> R (in MHS1; dbSNP:rs118192177).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_008973.
FT   VARIANT    2214   2214       V -> I (in MHS1; dbSNP:rs193922795).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:15448513}.
FT                                /FTId=VAR_045714.
FT   VARIANT    2248   2248       R -> C (in dbSNP:rs763352221).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071735.
FT   VARIANT    2248   2248       R -> H (in MHS1; unknown pathological
FT                                significance; dbSNP:rs140152019).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071736.
FT   VARIANT    2280   2280       V -> I (in MHS1; dbSNP:rs193922797).
FT                                {ECO:0000269|PubMed:12208234}.
FT                                /FTId=VAR_045715.
FT   VARIANT    2321   2321       I -> V (in dbSNP:rs34390345).
FT                                {ECO:0000269|PubMed:19191329,
FT                                ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_058567.
FT   VARIANT    2336   2336       R -> H (in MHS1; dbSNP:rs112563513).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058568.
FT   VARIANT    2342   2342       N -> S (in MHS1; dbSNP:rs147213895).
FT                                {ECO:0000269|PubMed:15221887}.
FT                                /FTId=VAR_045716.
FT   VARIANT    2344   2344       E -> D (in MHS1; unknown pathological
FT                                significance; dbSNP:rs193922798).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045717.
FT   VARIANT    2346   2346       V -> M (in MHS1; dbSNP:rs193922799).
FT                                {ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045718.
FT   VARIANT    2347   2347       Missing (in MHS1).
FT                                {ECO:0000269|PubMed:11389482}.
FT                                /FTId=VAR_045719.
FT   VARIANT    2348   2348       E -> G (in MHS1; dbSNP:rs193922801).
FT                                {ECO:0000269|PubMed:14985404}.
FT                                /FTId=VAR_045720.
FT   VARIANT    2350   2350       A -> T (in MHS1; reveals an altered
FT                                calcium dependence and increased caffeine
FT                                sensitivity; increases calcium-induced
FT                                calcium release activity;
FT                                dbSNP:rs193922802).
FT                                {ECO:0000269|PubMed:11525881,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:27586648}.
FT                                /FTId=VAR_045721.
FT   VARIANT    2351   2351       N -> H (in MHS1; unknown pathological
FT                                significance; dbSNP:rs376176332).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071738.
FT   VARIANT    2354   2354       V -> M (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071739.
FT   VARIANT    2355   2355       R -> C (in MHS1).
FT                                {ECO:0000269|PubMed:12123492}.
FT                                /FTId=VAR_045722.
FT   VARIANT    2358   2358       I -> L (in MHS1; unknown pathological
FT                                significance; dbSNP:rs759306349).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071740.
FT   VARIANT    2367   2367       A -> T (in MHS1; dbSNP:rs146306934).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:15448513}.
FT                                /FTId=VAR_045723.
FT   VARIANT    2375   2375       G -> A (increases calcium-induced calcium
FT                                release activity; dbSNP:rs193922807).
FT                                {ECO:0000269|PubMed:27586648}.
FT                                /FTId=VAR_077682.
FT   VARIANT    2383   2383       A -> Q (in MHS1; requires 2 nucleotide
FT                                substitutions; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071741.
FT   VARIANT    2400   2400       D -> G (in MHS1).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071742.
FT   VARIANT    2404   2404       E -> K (in MHS1; dbSNP:rs111364296).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058569.
FT   VARIANT    2421   2421       A -> P (in CCD; autosomal recessive form;
FT                                dbSNP:rs193922808).
FT                                {ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045724.
FT   VARIANT    2423   2423       M -> K (in MMDO and CCD; autosomal
FT                                recessive form; dbSNP:rs118192174).
FT                                {ECO:0000269|PubMed:16380615,
FT                                ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_032915.
FT   VARIANT    2428   2428       A -> T (in MHS1; induces an increase
FT                                sensitivity to caffeine;
FT                                dbSNP:rs193922809).
FT                                {ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045725.
FT   VARIANT    2431   2431       D -> N (in MHS1; dbSNP:rs193922810).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:15448513}.
FT                                /FTId=VAR_045726.
FT   VARIANT    2434   2434       G -> R (in MHS1; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs121918593).
FT                                {ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:7849712,
FT                                ECO:0000269|PubMed:7881417}.
FT                                /FTId=VAR_005605.
FT   VARIANT    2435   2435       R -> H (in CCD and MHS1; increases
FT                                calcium-induced calcium release activity;
FT                                dbSNP:rs28933396).
FT                                {ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:8220422}.
FT                                /FTId=VAR_005606.
FT   VARIANT    2435   2435       R -> L (in MHS1; dbSNP:rs28933396).
FT                                {ECO:0000269|PubMed:10051009,
FT                                ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:12709367}.
FT                                /FTId=VAR_008974.
FT   VARIANT    2437   2437       A -> V (in MHS1; dbSNP:rs193922812).
FT                                {ECO:0000269|PubMed:15448513}.
FT                                /FTId=VAR_045727.
FT   VARIANT    2452   2452       R -> W (in MHS1; dbSNP:rs118192124).
FT                                {ECO:0000269|PubMed:10823104,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:14985404}.
FT                                /FTId=VAR_045728.
FT   VARIANT    2454   2454       R -> C (in MHS1; induces an increase
FT                                sensitivity to caffeine; increases
FT                                calcium-induced calcium release activity;
FT                                dbSNP:rs193922816).
FT                                {ECO:0000269|PubMed:10612851,
FT                                ECO:0000269|PubMed:12411788,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:27586648}.
FT                                /FTId=VAR_008975.
FT   VARIANT    2454   2454       R -> H (in MHS1; severe form; increases
FT                                calcium-induced calcium release activity;
FT                                dbSNP:rs118192122).
FT                                {ECO:0000269|PubMed:10051009,
FT                                ECO:0000269|PubMed:10823104,
FT                                ECO:0000269|PubMed:11575529,
FT                                ECO:0000269|PubMed:12059893,
FT                                ECO:0000269|PubMed:12709367,
FT                                ECO:0000269|PubMed:15448513,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:27586648}.
FT                                /FTId=VAR_008976.
FT   VARIANT    2458   2458       R -> C (in MHS1; dbSNP:rs28933397).
FT                                {ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:9450902}.
FT                                /FTId=VAR_008977.
FT   VARIANT    2458   2458       R -> H (in MHS1; dbSNP:rs121918594).
FT                                {ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:27586648,
FT                                ECO:0000269|PubMed:9450902}.
FT                                /FTId=VAR_008978.
FT   VARIANT    2508   2508       R -> C (in MHS1 and CCD; increases
FT                                sensitivity to caffeine and 4-chloro-m-
FT                                cresol; decreases protein abundance;
FT                                increases calcium-induced calcium release
FT                                activity; dbSNP:rs118192178).
FT                                {ECO:0000269|PubMed:19685112,
FT                                ECO:0000269|PubMed:26381711,
FT                                ECO:0000269|PubMed:27586648}.
FT                                /FTId=VAR_075399.
FT   VARIANT    2508   2508       R -> G (in CCD; increases sensitivity to
FT                                caffeine and 4-chloro-m-cresol;
FT                                dbSNP:rs118192178).
FT                                {ECO:0000269|PubMed:20142353,
FT                                ECO:0000269|PubMed:26381711}.
FT                                /FTId=VAR_068516.
FT   VARIANT    2508   2508       R -> H (in MHS1; increases sensitivity to
FT                                caffeine and 4-chloro-m-cresol; decreases
FT                                protein abundance; increases calcium-
FT                                induced calcium release activity;
FT                                dbSNP:rs193922818).
FT                                {ECO:0000269|PubMed:26381711,
FT                                ECO:0000269|PubMed:27586648}.
FT                                /FTId=VAR_077683.
FT   VARIANT    2509   2509       V -> I (in dbSNP:rs2071088).
FT                                /FTId=VAR_051891.
FT   VARIANT    2550   2550       L -> V (in dbSNP:rs193922821).
FT                                {ECO:0000269|PubMed:1354642,
FT                                ECO:0000269|PubMed:19191329,
FT                                ECO:0000269|PubMed:8661021}.
FT                                /FTId=VAR_058570.
FT   VARIANT    2593   2593       R -> G (in MHS1).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071743.
FT   VARIANT    2627   2627       V -> M (in MHS1).
FT                                {ECO:0000269|PubMed:24013571}.
FT                                /FTId=VAR_071744.
FT   VARIANT    2676   2676       R -> W (in MHS1; located on the same
FT                                allele as S-2787; dbSNP:rs28934001).
FT                                {ECO:0000269|PubMed:14732627,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_045729.
FT   VARIANT    2730   2730       D -> G (in MHS1; dbSNP:rs112196644).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058571.
FT   VARIANT    2779   2779       E -> K (in dbSNP:rs2915952).
FT                                /FTId=VAR_051892.
FT   VARIANT    2787   2787       T -> S (in MHS1; located on the same
FT                                allele as W-2676; dbSNP:rs35180584).
FT                                {ECO:0000269|PubMed:14732627,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_045730.
FT   VARIANT    2880   2880       E -> K (in MHS1; dbSNP:rs112772310).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058572.
FT   VARIANT    2963   2963       L -> P (in CCD; dbSNP:rs756870293).
FT                                {ECO:0000269|PubMed:27234031}.
FT                                /FTId=VAR_076568.
FT   VARIANT    2976   2976       H -> Y. {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071745.
FT   VARIANT    3118   3118       A -> V (in dbSNP:rs2915960).
FT                                /FTId=VAR_045731.
FT   VARIANT    3217   3217       S -> P (in MHS1; dbSNP:rs113422327).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058573.
FT   VARIANT    3238   3238       E -> G (in CCD; unknown pathological
FT                                significance; dbSNP:rs200950673).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071746.
FT   VARIANT    3290   3290       E -> K (in MHS1; dbSNP:rs112151058).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058574.
FT   VARIANT    3326   3326       N -> K (in MMDO; dbSNP:rs367543057).
FT                                {ECO:0000269|PubMed:20583297}.
FT                                /FTId=VAR_063848.
FT   VARIANT    3360   3360       P -> Q. {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071747.
FT   VARIANT    3366   3366       R -> H (in CCD; dbSNP:rs137932199).
FT                                {ECO:0000269|PubMed:21674524}.
FT                                /FTId=VAR_068517.
FT   VARIANT    3402   3402       C -> G (in MMDO; dbSNP:rs367543058).
FT                                {ECO:0000269|PubMed:20583297}.
FT                                /FTId=VAR_063849.
FT   VARIANT    3410   3410       P -> Q (in MHS1).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071748.
FT   VARIANT    3501   3501       D -> Y (in MHS1; dbSNP:rs763259167).
FT                                {ECO:0000269|PubMed:20681998}.
FT                                /FTId=VAR_071749.
FT   VARIANT    3527   3527       P -> S (in CCD; autosomal recessive form;
FT                                dbSNP:rs118192164).
FT                                {ECO:0000269|PubMed:12112081}.
FT                                /FTId=VAR_045732.
FT   VARIANT    3539   3539       R -> H (in CCD; autosomal recessive form;
FT                                dbSNP:rs143987857).
FT                                {ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045733.
FT   VARIANT    3583   3583       E -> Q (in dbSNP:rs55876273).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058575.
FT   VARIANT    3711   3711       T -> R (in MHS1; unknown pathological
FT                                significance; dbSNP:rs375915752).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071750.
FT   VARIANT    3756   3756       Q -> E (in dbSNP:rs4802584).
FT                                {ECO:0000269|PubMed:11928716,
FT                                ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_032916.
FT   VARIANT    3772   3772       R -> Q (in CCD; autosomal recessive form;
FT                                dbSNP:rs193922839).
FT                                {ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045734.
FT   VARIANT    3772   3772       R -> W (in MHS1; dbSNP:rs763112609).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058576.
FT   VARIANT    3806   3806       G -> R (in MHS1; dbSNP:rs111565359).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058577.
FT   VARIANT    3916   3916       I -> M (in MHS1; dbSNP:rs193922840).
FT                                {ECO:0000269|PubMed:12411788,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045735.
FT   VARIANT    3933   3933       Y -> C (in CCD and MHS1;
FT                                dbSNP:rs147136339).
FT                                {ECO:0000269|PubMed:20681998,
FT                                ECO:0000269|PubMed:21674524}.
FT                                /FTId=VAR_068518.
FT   VARIANT    4136   4136       R -> S (in MHS1; dbSNP:rs193922849).
FT                                {ECO:0000269|PubMed:12208234}.
FT                                /FTId=VAR_045736.
FT   VARIANT    4178   4178       G -> V (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071751.
FT   VARIANT    4214   4216       Missing (in CCD).
FT                                /FTId=VAR_045737.
FT   VARIANT    4230   4230       M -> R (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071752.
FT   VARIANT    4234   4234       V -> L (in MHS1; dbSNP:rs193922852).
FT                                {ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:24013571}.
FT                                /FTId=VAR_045738.
FT   VARIANT    4493   4493       P -> A (in dbSNP:rs149455643).
FT                                {ECO:0000269|PubMed:21674524}.
FT                                /FTId=VAR_068519.
FT   VARIANT    4501   4501       P -> L (in MHS1; dbSNP:rs73933023).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058578.
FT   VARIANT    4558   4558       R -> Q (in CCD; autosomal recessive form;
FT                                dbSNP:rs118192130).
FT                                {ECO:0000269|PubMed:17226826,
FT                                ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045739.
FT   VARIANT    4637   4637       T -> A (in CCD; dbSNP:rs118192166).
FT                                {ECO:0000269|PubMed:11113224}.
FT                                /FTId=VAR_045740.
FT   VARIANT    4637   4637       T -> I (in core/rod disease;
FT                                dbSNP:rs118192134).
FT                                {ECO:0000269|PubMed:12565913}.
FT                                /FTId=VAR_045741.
FT   VARIANT    4638   4638       G -> D (in CCD; dbSNP:rs118192135).
FT                                {ECO:0000269|PubMed:12565913,
FT                                ECO:0000269|PubMed:14985404}.
FT                                /FTId=VAR_045742.
FT   VARIANT    4647   4648       Missing (in CCD).
FT                                {ECO:0000269|PubMed:11709545}.
FT                                /FTId=VAR_045743.
FT   VARIANT    4650   4650       L -> P (in CCD; autosomal recessive form;
FT                                dbSNP:rs118192138).
FT                                {ECO:0000269|PubMed:12937085}.
FT                                /FTId=VAR_045744.
FT   VARIANT    4651   4651       H -> P (in CCD; dbSNP:rs118192139).
FT                                {ECO:0000269|PubMed:12565913}.
FT                                /FTId=VAR_045745.
FT   VARIANT    4668   4668       P -> S (in dbSNP:rs193922863).
FT                                {ECO:0000269|PubMed:11928716}.
FT                                /FTId=VAR_045746.
FT   VARIANT    4684   4684       F -> S (in MHS1; dbSNP:rs193922864).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045747.
FT   VARIANT    4724   4724       K -> Q (in CCD; autosomal recessive form;
FT                                dbSNP:rs118192141).
FT                                {ECO:0000269|PubMed:12937085}.
FT                                /FTId=VAR_045748.
FT   VARIANT    4737   4737       R -> Q (in MHS1; dbSNP:rs193922868).
FT                                {ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045749.
FT   VARIANT    4737   4737       R -> W (in MHS1; unknown pathological
FT                                significance; slightly increases Ca(2+)
FT                                release in response to 4-chloro-m-cresol;
FT                                dbSNP:rs193922867).
FT                                {ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:26631338}.
FT                                /FTId=VAR_045750.
FT   VARIANT    4743   4743       G -> D (in CCD; dbSNP:rs193922869).
FT                                {ECO:0000269|PubMed:21674524}.
FT                                /FTId=VAR_068520.
FT   VARIANT    4793   4793       L -> P (in CCD; dbSNP:rs118192179).
FT                                {ECO:0000269|PubMed:11709545}.
FT                                /FTId=VAR_045751.
FT   VARIANT    4796   4796       Y -> C (in CCD; dbSNP:rs118192167).
FT                                {ECO:0000269|PubMed:11709545}.
FT                                /FTId=VAR_045752.
FT   VARIANT    4806   4806       N -> D (in CCD).
FT                                {ECO:0000269|PubMed:27234031}.
FT                                /FTId=VAR_076569.
FT   VARIANT    4814   4814       L -> F (in CCD; dbSNP:rs118192142).
FT                                {ECO:0000269|PubMed:14985404}.
FT                                /FTId=VAR_045753.
FT   VARIANT    4824   4824       L -> P (in MHS1; dbSNP:rs193922874).
FT                                {ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:15448513}.
FT                                /FTId=VAR_045754.
FT   VARIANT    4825   4825       R -> C (in CCD; dbSNP:rs118192180).
FT                                {ECO:0000269|PubMed:11709545}.
FT                                /FTId=VAR_045755.
FT   VARIANT    4826   4826       T -> I (in MHS1; dbSNP:rs121918595).
FT                                {ECO:0000269|PubMed:10888602,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045756.
FT   VARIANT    4837   4837       Q -> E (in MHS1; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071753.
FT   VARIANT    4838   4838       L -> V (in MHS1; dbSNP:rs193922878).
FT                                {ECO:0000269|PubMed:11928716,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_045757.
FT   VARIANT    4842   4842       V -> M (in CCD; autosomal recessive form;
FT                                dbSNP:rs193922879).
FT                                {ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045758.
FT   VARIANT    4846   4846       A -> V (in CCD; autosomal recessive form;
FT                                dbSNP:rs118192143).
FT                                {ECO:0000269|PubMed:17204054,
FT                                ECO:0000269|PubMed:17226826}.
FT                                /FTId=VAR_045759.
FT   VARIANT    4849   4849       V -> I (in MHS1 and CCD; autosomal
FT                                recessive form; dbSNP:rs118192168).
FT                                {ECO:0000269|PubMed:12136074,
FT                                ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:17226826,
FT                                ECO:0000269|PubMed:18253926}.
FT                                /FTId=VAR_045760.
FT   VARIANT    4860   4860       Missing (in CCD).
FT                                {ECO:0000269|PubMed:11709545}.
FT                                /FTId=VAR_045761.
FT   VARIANT    4861   4861       R -> C (in CCD; dbSNP:rs118192181).
FT                                {ECO:0000269|PubMed:12565913,
FT                                ECO:0000269|PubMed:17226826}.
FT                                /FTId=VAR_045762.
FT   VARIANT    4861   4861       R -> H (in CCD and MHS1; release of
FT                                calcium from intracellular stores in the
FT                                absence of any pharmacological activator
FT                                of RYR; dbSNP:rs63749869).
FT                                {ECO:0000269|PubMed:11709545,
FT                                ECO:0000269|PubMed:11741831,
FT                                ECO:0000269|PubMed:12565913,
FT                                ECO:0000269|PubMed:14670767,
FT                                ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:17226826,
FT                                ECO:0000269|PubMed:23558838,
FT                                ECO:0000269|PubMed:24561095}.
FT                                /FTId=VAR_045763.
FT   VARIANT    4863   4869       FYNKSED -> Y (in CCD).
FT                                /FTId=VAR_045764.
FT   VARIANT    4864   4864       Y -> C (in CCD; dbSNP:rs118192146).
FT                                {ECO:0000269|PubMed:14670767}.
FT                                /FTId=VAR_045765.
FT   VARIANT    4876   4876       K -> R (in MHS1; dbSNP:rs113210953).
FT                                {ECO:0000269|PubMed:16163667,
FT                                ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_045766.
FT   VARIANT    4882   4882       T -> M (in CCD; dbSNP:rs193922884).
FT                                {ECO:0000269|PubMed:18312400}.
FT                                /FTId=VAR_068521.
FT   VARIANT    4891   4891       G -> R (in CCD; dbSNP:rs118192149).
FT                                {ECO:0000269|PubMed:11741831}.
FT                                /FTId=VAR_045767.
FT   VARIANT    4893   4893       R -> Q (in CCD; dbSNP:rs118192151).
FT                                {ECO:0000269|PubMed:12565913}.
FT                                /FTId=VAR_045768.
FT   VARIANT    4893   4893       R -> W (in CCD; release of calcium from
FT                                intracellular stores in the absence of
FT                                any pharmacological activator of RYR;
FT                                smaller thapsigargin-sensitive
FT                                intracellular calcium stores; normal
FT                                sensitivity of the calcium release to the
FT                                RYR inhibitor dantrolene;
FT                                dbSNP:rs118192150).
FT                                {ECO:0000269|PubMed:11709545,
FT                                ECO:0000269|PubMed:11741831,
FT                                ECO:0000269|PubMed:14670767}.
FT                                /FTId=VAR_045769.
FT   VARIANT    4897   4897       G -> A (in CCD).
FT                                {ECO:0000269|PubMed:24561095}.
FT                                /FTId=VAR_071754.
FT   VARIANT    4897   4897       G -> V (in CCD; dbSNP:rs118192148).
FT                                {ECO:0000269|PubMed:17226826}.
FT                                /FTId=VAR_045770.
FT   VARIANT    4898   4898       I -> T (in CCD; severe phenotype;
FT                                dbSNP:rs118192170).
FT                                {ECO:0000269|PubMed:10097181,
FT                                ECO:0000269|PubMed:11709545,
FT                                ECO:0000269|PubMed:11741831,
FT                                ECO:0000269|PubMed:12565913,
FT                                ECO:0000269|PubMed:24561095}.
FT                                /FTId=VAR_045771.
FT   VARIANT    4899   4899       G -> E (in CCD; dbSNP:rs118192183).
FT                                {ECO:0000269|PubMed:11709545,
FT                                ECO:0000269|PubMed:12937085}.
FT                                /FTId=VAR_045772.
FT   VARIANT    4899   4899       G -> R (in CCD; release of calcium from
FT                                intracellular stores in the absence of
FT                                any pharmacological activator of RYR;
FT                                smaller thapsigargin-sensitive
FT                                intracellular calcium stores; normal
FT                                sensitivity of the calcium release to the
FT                                RYR inhibitor dantrolene;
FT                                dbSNP:rs193922891).
FT                                {ECO:0000269|PubMed:11741831}.
FT                                /FTId=VAR_045773.
FT   VARIANT    4906   4906       A -> G (in MHS1; unknown pathological
FT                                significance; dbSNP:rs118192153).
FT                                {ECO:0000269|PubMed:23558838}.
FT                                /FTId=VAR_071755.
FT   VARIANT    4906   4906       A -> V (in CCD; dbSNP:rs118192153).
FT                                {ECO:0000269|PubMed:11741831}.
FT                                /FTId=VAR_045774.
FT   VARIANT    4914   4914       R -> G (in CCD; dbSNP:rs118192184).
FT                                {ECO:0000269|PubMed:11709545,
FT                                ECO:0000269|PubMed:12565913}.
FT                                /FTId=VAR_045775.
FT   VARIANT    4914   4914       R -> T (in CCD; dbSNP:rs118192154).
FT                                {ECO:0000269|PubMed:12565913,
FT                                ECO:0000269|PubMed:17226826}.
FT                                /FTId=VAR_045776.
FT   VARIANT    4927   4928       Missing (in CCD).
FT                                {ECO:0000269|PubMed:12565913}.
FT                                /FTId=VAR_045777.
FT   VARIANT    4938   4938       I -> M (in CCD; dbSNP:rs118192159).
FT                                {ECO:0000269|PubMed:14985404}.
FT                                /FTId=VAR_045778.
FT   VARIANT    4938   4938       I -> T (in MHS1; dbSNP:rs111657878).
FT                                {ECO:0000269|PubMed:19191329}.
FT                                /FTId=VAR_058579.
FT   VARIANT    4939   4939       D -> E (in MHS1; dbSNP:rs193922895).
FT                                {ECO:0000269|PubMed:14985404,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045779.
FT   VARIANT    4940   4940       A -> T (in CCD; dbSNP:rs118192158).
FT                                {ECO:0000269|PubMed:12565913,
FT                                ECO:0000269|PubMed:14670767}.
FT                                /FTId=VAR_045780.
FT   VARIANT    4942   4942       G -> V (in MHS1; dbSNP:rs193922896).
FT                                {ECO:0000269|PubMed:12208234}.
FT                                /FTId=VAR_045781.
FT   VARIANT    4973   4973       P -> L (in MHS1; dbSNP:rs146876145).
FT                                {ECO:0000269|PubMed:12208234,
FT                                ECO:0000269|PubMed:12411788,
FT                                ECO:0000269|PubMed:16163667}.
FT                                /FTId=VAR_045782.
FT   MUTAGEN     522    522       Y->C: Increases calcium-induced calcium
FT                                release activity.
FT                                {ECO:0000269|PubMed:26115329}.
FT   MUTAGEN    2508   2508       R->K: Increases sensitivity to caffeine
FT                                and 4-chloro-m-cresol.
FT                                {ECO:0000269|PubMed:26381711}.
FT   MUTAGEN    2508   2508       R->S: Increases sensitivity to caffeine
FT                                and 4-chloro-m-cresol.
FT                                {ECO:0000269|PubMed:26381711}.
FT   CONFLICT   1365   1368       GEAQ -> RGA (in Ref. 1; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT   2324   2324       N -> K (in Ref. 1; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT   2840   2840       R -> A (in Ref. 1; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT   3380   3380       R -> A (in Ref. 1; AA sequence).
FT                                {ECO:0000305}.
SQ   SEQUENCE   5038 AA;  565176 MW;  EC32277F4885CC7F CRC64;
     MGDAEGEDEV QFLRTDDEVV LQCSATVLKE QLKLCLAAEG FGNRLCFLEP TSNAQNVPPD
     LAICCFVLEQ SLSVRALQEM LANTVEAGVE SSQGGGHRTL LYGHAILLRH AHSRMYLSCL
     TTSRSMTDKL AFDVGLQEDA TGEACWWTMH PASKQRSEGE KVRVGDDIIL VSVSSERYLH
     LSTASGELQV DASFMQTLWN MNPICSRCEE GFVTGGHVLR LFHGHMDECL TISPADSDDQ
     RRLVYYEGGA VCTHARSLWR LEPLRISWSG SHLRWGQPLR VRHVTTGQYL ALTEDQGLVV
     VDASKAHTKA TSFCFRISKE KLDVAPKRDV EGMGPPEIKY GESLCFVQHV ASGLWLTYAA
     PDPKALRLGV LKKKAMLHQE GHMDDALSLT RCQQEESQAA RMIHSTNGLY NQFIKSLDSF
     SGKPRGSGPP AGTALPIEGV ILSLQDLIIY FEPPSEDLQH EEKQSKLRSL RNRQSLFQEE
     GMLSMVLNCI DRLNVYTTAA HFAEFAGEEA AESWKEIVNL LYELLASLIR GNRSNCALFS
     TNLDWLVSKL DRLEASSGIL EVLYCVLIES PEVLNIIQEN HIKSIISLLD KHGRNHKVLD
     VLCSLCVCNG VAVRSNQDLI TENLLPGREL LLQTNLINYV TSIRPNIFVG RAEGTTQYSK
     WYFEVMVDEV TPFLTAQATH LRVGWALTEG YTPYPGAGEG WGGNGVGDDL YSYGFDGLHL
     WTGHVARPVT SPGQHLLAPE DVISCCLDLS VPSISFRING CPVQGVFESF NLDGLFFPVV
     SFSAGVKVRF LLGGRHGEFK FLPPPGYAPC HEAVLPRERL HLEPIKEYRR EGPRGPHLVG
     PSRCLSHTDF VPCPVDTVQI VLPPHLERIR EKLAENIHEL WALTRIEQGW TYGPVRDDNK
     RLHPCLVDFH SLPEPERNYN LQMSGETLKT LLALGCHVGM ADEKAEDNLK KTKLPKTYMM
     SNGYKPAPLD LSHVRLTPAQ TTLVDRLAEN GHNVWARDRV GQGWSYSAVQ DIPARRNPRL
     VPYRLLDEAT KRSNRDSLCQ AVRTLLGYGY NIEPPDQEPS QVENQSRCDR VRIFRAEKSY
     TVQSGRWYFE FEAVTTGEMR VGWARPELRP DVELGADELA YVFNGHRGQR WHLGSEPFGR
     PWQPGDVVGC MIDLTENTII FTLNGEVLMS DSGSETAFRE IEIGDGFLPV CSLGPGQVGH
     LNLGQDVSSL RFFAICGLQE GFEPFAINMQ RPVTTWFSKG LPQFEPVPLE HPHYEVSRVD
     GTVDTPPCLR LTHRTWGSQN SLVEMLFLRL SLPVQFHQHF RCTAGATPLA PPGLQPPAED
     EARAAEPDPD YENLRRSAGG WSEAENGKEG TAKEGAPGGT PQAGGEAQPA RAENEKDATT
     EKNKKRGFLF KAKKVAMMTQ PPATPTLPRL PHDVVPADNR DDPEIILNTT TYYYSVRVFA
     GQEPSCVWAG WVTPDYHQHD MSFDLSKVRV VTVTMGDEQG NVHSSLKCSN CYMVWGGDFV
     SPGQQGRISH TDLVIGCLVD LATGLMTFTA NGKESNTFFQ VEPNTKLFPA VFVLPTHQNV
     IQFELGKQKN IMPLSAAMFQ SERKNPAPQC PPRLEMQMLM PVSWSRMPNH FLQVETRRAG
     ERLGWAVQCQ EPLTMMALHI PEENRCMDIL ELSERLDLQR FHSHTLRLYR AVCALGNNRV
     AHALCSHVDQ AQLLHALEDA HLPGPLRAGY YDLLISIHLE SACRSRRSML SEYIVPLTPE
     TRAITLFPPG RSTENGHPRH GLPGVGVTTS LRPPHHFSPP CFVAALPAAG AAEAPARLSP
     AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGIFGDEDVK
     QILKMIEPEV FTEEEEEEDE EEEGEEEDEE EKEEDEEETA QEKEDEEKEE EEAAEGEKEE
     GLEEGLLQMK LPESVKLQMC HLLEYFCDQE LQHRVESLAA FAERYVDKLQ ANQRSRYGLL
     IKAFSMTAAE TARRTREFRS PPQEQINMLL QFKDGTDEED CPLPEEIRQD LLDFHQDLLA
     HCGIQLDGEE EEPEEETTLG SRLMSLLEKV RLVKKKEEKP EEERSAEESK PRSLQELVSH
     MVVRWAQEDF VQSPELVRAM FSLLHRQYDG LGELLRALPR AYTISPSSVE DTMSLLECLG
     QIRSLLIVQM GPQEENLMIQ SIGNIMNNKV FYQHPNLMRA LGMHETVMEV MVNVLGGGES
     KEIRFPKMVT SCCRFLCYFC RISRQNQRSM FDHLSYLLEN SGIGLGMQGS TPLDVAAASV
     IDNNELALAL QEQDLEKVVS YLAGCGLQSC PMLVAKGYPD IGWNPCGGER YLDFLRFAVF
     VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGIRRD
     RRREHFGEEP PEENRVHLGH AIMSFYAALI DLLGRCAPEM HLIQAGKGEA LRIRAILRSL
     VPLEDLVGII SLPLQIPTLG KDGALVQPKM SASFVPDHKA SMVLFLDRVY GIENQDFLLH
     VLDVGFLPDM RAAASLDTAT FSTTEMALAL NRYLCLAVLP LITKCAPLFA GTEHRAIMVD
     SMLHTVYRLS RGRSLTKAQR DVIEDCLMSL CRYIRPSMLQ HLLRRLVFDV PILNEFAKMP
     LKLLTNHYER CWKYYCLPTG WANFGVTSEE ELHLTRKLFW GIFDSLAHKK YDPELYRMAM
     PCLCAIAGAL PPDYVDASYS SKAEKKATVD AEGNFDPRPV ETLNVIIPEK LDSFINKFAE
     YTHEKWAFDK IQNNWSYGEN IDEELKTHPM LRPYKTFSEK DKEIYRWPIK ESLKAMIAWE
     WTIEKAREGE EEKTEKKKTR KISQSAQTYD PREGYNPQPP DLSAVTLSRE LQAMAEQLAE
     NYHNTWGRKK KQELEAKGGG THPLLVPYDT LTAKEKARDR EKAQELLKFL QMNGYAVTRG
     LKDMELDSSS IEKRFAFGFL QQLLRWMDIS QEFIAHLEAV VSSGRVEKSP HEQEIKFFAK
     ILLPLINQYF TNHCLYFLST PAKVLGSGGH ASNKEKEMIT SLFCKLAALV RHRVSLFGTD
     APAVVNCLHI LARSLDARTV MKSGPEIVKA GLRSFFESAS EDIEKMVENL RLGKVSQART
     QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTKN
     TYVEKLRPAL GECLARLAAA MPVAFLEPQL NEYNACSVYT TKSPRERAIL GLPNSVEEMC
     PDIPVLERLM ADIGGLAESG ARYTEMPHVI EITLPMLCSY LPRWWERGPE APPSALPAGA
     PPPCTAVTSD HLNSLLGNIL RIIVNNLGID EASWMKRLAV FAQPIVSRAR PELLQSHFIP
     TIGRLRKRAG KVVSEEEQLR LEAKAEAQEG ELLVRDEFSV LCRDLYALYP LLIRYVDNNR
     AQWLTEPNPS AEELFRMVGE IFIYWSKSHN FKREEQNFVV QNEINNMSFL TADNKSKMAK
     AGDIQSGGSD QERTKKKRRG DRYSVQTSLI VATLKKMLPI GLNMCAPTDQ DLITLAKTRY
     ALKDTDEEVR EFLHNNLHLQ GKVEGSPSLR WQMALYRGVP GREEDADDPE KIVRRVQEVS
     AVLYYLDQTE HPYKSKKAVW HKLLSKQRRR AVVACFRMTP LYNLPTHRAC NMFLESYKAA
     WILTEDHSFE DRMIDDLSKA GEQEEEEEEV EEKKPDPLHQ LVLHFSRTAL TEKSKLDEDY
     LYMAYADIMA KSCHLEEGGE NGEAEEEVEV SFEEKQMEKQ RLLYQQARLH TRGAAEMVLQ
     MISACKGETG AMVSSTLKLG ISILNGGNAE VQQKMLDYLK DKKEVGFFQS IQALMQTCSV
     LDLNAFERQN KAEGLGMVNE DGTVINRQNG EKVMADDEFT QDLFRFLQLL CEGHNNDFQN
     YLRTQTGNTT TINIIICTVD YLLRLQESIS DFYWYYSGKD VIEEQGKRNF SKAMSVAKQV
     FNSLTEYIQG PCTGNQQSLA HSRLWDAVVG FLHVFAHMMM KLAQDSSQIE LLKELLDLQK
     DMVVMLLSLL EGNVVNGMIA RQMVDMLVES SSNVEMILKF FDMFLKLKDI VGSEAFQDYV
     TDPRGLISKK DFQKAMDSQK QFSGPEIQFL LSCSEADENE MINCEEFANR FQEPARDIGF
     NVAVLLTNLS EHVPHDPRLH NFLELAESIL EYFRPYLGRI EIMGASRRIE RIYFEISETN
     RAQWEMPQVK ESKRQFIFDV VNEGGEAEKM ELFVSFCEDT IFEMQIAAQI SEPEGEPETD
     EDEGAGAAEA GAEGAEEGAA GLEGTAATAA AGATARVVAA AGRALRGLSY RSLRRRVRRL
     RRLTAREAAT AVAALLWAAV TRAGAAGAGA AAGALGLLWG SLFGGGLVEG AKKVTVTELL
     AGMPDPTSDE VHGEQPAGPG GDADGEGASE GAGDAAEGAG DEEEAVHEAG PGGADGAVAV
     TDGGPFRPEG AGGLGDMGDT TPAEPPTPEG SPILKRKLGV DGVEEELPPE PEPEPEPELE
     PEKADAENGE KEEVPEPTPE PPKKQAPPSP PPKKEEAGGE FWGELEVQRV KFLNYLSRNF
     YTLRFLALFL AFAINFILLF YKVSDSPPGE DDMEGSAAGD VSGAGSGGSS GWGLGAGEEA
     EGDEDENMVY YFLEESTGYM EPALRCLSLL HTLVAFLCII GYNCLKVPLV IFKREKELAR
     KLEFDGLYIT EQPEDDDVKG QWDRLVLNTP SFPSNYWDKF VKRKVLDKHG DIYGRERIAE
     LLGMDLATLE ITAHNERKPN PPPGLLTWLM SIDVKYQIWK FGVIFTDNSF LYLGWYMVMS
     LLGHYNNFFF AAHLLDIAMG VKTLRTILSS VTHNGKQLVM TVGLLAVVVY LYTVVAFNFF
     RKFYNKSEDE DEPDMKCDDM MTCYLFHMYV GVRAGGGIGD EIEDPAGDEY ELYRVVFDIT
     FFFFVIVILL AIIQGLIIDA FGELRDQQEQ VKEDMETKCF ICGIGSDYFD TTPHGFETHT
     LEEHNLANYM FFLMYLINKD ETEHTGQESY VWKMYQERCW DFFPAGDCFR KQYEDQLS
//
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