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 28-FEB-2018, entry version 208.
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.
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 CCD GLY-2508, CHARACTERIZATION OF VARIANT
RP MHS1 HIS-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; 9.
DR DIP; DIP-29708N; -.
DR ELM; P21817; -.
DR IntAct; P21817; 12.
DR MINT; P21817; -.
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 CarbonylDB; P21817; -.
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 EuPathDB; HostDB:ENSG00000196218.11; -.
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; HDA: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 CDD; cd12877; SPRY1_RyR; 1.
DR CDD; cd12878; SPRY2_RyR; 1.
DR CDD; cd12879; SPRY3_RyR; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
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; IPR036300; MIR_dom_sf.
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; IPR035910; RyR/IP3R_RIH_dom_sf.
DR InterPro; IPR033215; RyR1.
DR InterPro; IPR035761; SPRY1_RyR.
DR InterPro; IPR035764; SPRY2_RyR.
DR InterPro; IPR035762; SPRY3_RyR.
DR InterPro; IPR003877; SPRY_dom.
DR PANTHER; PTHR13715; PTHR13715; 1.
DR PANTHER; PTHR13715:SF15; PTHR13715:SF15; 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:23558838,
FT ECO:0000269|PubMed:26115329,
FT ECO:0000269|PubMed:8220423,
FT ECO:0000305|PubMed:16163667}.
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:rs121918592).
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:rs118192172).
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:rs118192175).
FT {ECO:0000269|PubMed:15448513,
FT ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:9497245,
FT ECO:0000305|PubMed:27586648}.
FT /FTId=VAR_005601.
FT VARIANT 2163 2163 R -> H (in CCD and MHS1; increases
FT calcium-induced calcium release activity;
FT dbSNP:rs118192163).
FT {ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:16163667,
FT ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:9497245,
FT ECO:0000305|PubMed:27586648}.
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:9497245,
FT ECO:0000305|PubMed:27586648}.
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:rs118192177).
FT {ECO:0000269|PubMed:11575529,
FT ECO:0000269|PubMed:12059893,
FT ECO:0000269|PubMed:12208234,
FT ECO:0000269|PubMed:15448513,
FT ECO:0000269|PubMed:23558838,
FT ECO:0000269|PubMed:9497245,
FT ECO:0000305|PubMed:16163667,
FT ECO:0000305|PubMed:27586648}.
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:0000305|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:0000305|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; dbSNP:rs976108591).
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:0000305|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:7849712,
FT ECO:0000269|PubMed:7881417,
FT ECO:0000305|PubMed:27586648}.
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:8220422,
FT ECO:0000305|PubMed:27586648}.
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:0000305|PubMed:16163667,
FT ECO:0000305|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:23558838,
FT ECO:0000305|PubMed:16163667,
FT ECO:0000305|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:9450902,
FT ECO:0000305|PubMed:27586648}.
FT /FTId=VAR_008977.
FT VARIANT 2458 2458 R -> H (in MHS1; dbSNP:rs121918594).
FT {ECO:0000269|PubMed:14985404,
FT ECO:0000269|PubMed:9450902,
FT ECO:0000305|PubMed:27586648}.
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; increases calcium-induced calcium
FT release activity; dbSNP:rs118192178).
FT {ECO:0000269|PubMed:19685112,
FT ECO:0000305|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; increases
FT calcium-induced calcium release activity;
FT dbSNP:rs193922818).
FT {ECO:0000269|PubMed:26381711,
FT ECO:0000305|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:rs193922826).
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; dbSNP:rs886039586).
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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