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Database: UniProt
Entry: SCN4A_HUMAN
LinkDB: SCN4A_HUMAN
Original site: SCN4A_HUMAN 
ID   SCN4A_HUMAN             Reviewed;        1836 AA.
AC   P35499; Q15478; Q16447; Q7Z6B1;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 4.
DT   22-NOV-2017, entry version 184.
DE   RecName: Full=Sodium channel protein type 4 subunit alpha;
DE   AltName: Full=SkM1;
DE   AltName: Full=Sodium channel protein skeletal muscle subunit alpha;
DE   AltName: Full=Sodium channel protein type IV subunit alpha;
DE   AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.4;
GN   Name=SCN4A;
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 [GENOMIC DNA / MRNA], AND VARIANTS GLY-524;
RP   ASP-559 AND ASP-1376.
RC   TISSUE=Skeletal muscle;
RX   PubMed=1315496; DOI=10.1002/ana.410310203;
RA   George A.L. Jr., Komisarof J., Kallen R.G., Barchi R.L.;
RT   "Primary structure of the adult human skeletal muscle voltage-
RT   dependent sodium channel.";
RL   Ann. Neurol. 31:131-137(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1310396; DOI=10.1016/0006-291X(92)91802-W;
RA   Wang J., Rojas C.V., Zhou J., Schwartz L.S., Nicholas H.,
RA   Hoffmann E.P.;
RT   "Sequence and genomic structure of the human adult skeletal muscle
RT   sodium channel alpha subunit gene on 17q.";
RL   Biochem. Biophys. Res. Commun. 182:794-801(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMS16 GLU-1442, AND VARIANTS
RP   LEU-246; GLY-524 AND ASP-559.
RX   PubMed=12766226; DOI=10.1073/pnas.1230273100;
RA   Tsujino A., Maertens C., Ohno K., Shen X.-M., Fukuda T., Harper C.M.,
RA   Cannon S.C., Engel A.G.;
RT   "Myasthenic syndrome caused by mutation of the SCN4A sodium channel.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:7377-7382(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-524.
RX   PubMed=1339144; DOI=10.1093/hmg/1.7.521;
RA   McClatchey A.I., Lin C.S., Wang J., Hoffman E.P., Rojas C.V.,
RA   Gusella J.F.;
RT   "The genomic structure of the human skeletal muscle sodium channel
RT   gene.";
RL   Hum. Mol. Genet. 1:521-527(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA   Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA   Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA   Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA   Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA   Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA   Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA   Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT   the human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1305-1339, AND VARIANTS PMC
RP   VAL-1306 AND MET-1313.
RX   PubMed=1310898; DOI=10.1016/0092-8674(92)90151-2;
RA   McClatchey A.I., van den Bergh P., Pericak-Vance M.A., Raskind W.,
RA   Verellen C., McKenna-Yasek D., Rao K., Haines J.L., Bird T.,
RA   Brown R.H. Jr., Gusella J.F.;
RT   "Temperature-sensitive mutations in the III-IV cytoplasmic loop region
RT   of the skeletal muscle sodium channel gene in paramyotonia
RT   congenita.";
RL   Cell 68:769-774(1992).
RN   [7]
RP   INTERACTION WITH THE CONOTOXIN GVIIJ.
RX   PubMed=24497506; DOI=10.1073/pnas.1324189111;
RA   Gajewiak J., Azam L., Imperial J., Walewska A., Green B.R.,
RA   Bandyopadhyay P.K., Raghuraman S., Ueberheide B., Bern M., Zhou H.M.,
RA   Minassian N.A., Hagan R.H., Flinspach M., Liu Y., Bulaj G.,
RA   Wickenden A.D., Olivera B.M., Yoshikami D., Zhang M.M.;
RT   "A disulfide tether stabilizes the block of sodium channels by the
RT   conotoxin muO[section sign]-GVIIJ.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:2758-2763(2014).
RN   [8]
RP   VARIANT HYPP MET-704.
RX   PubMed=1659948; DOI=10.1016/0092-8674(91)90374-8;
RA   Ptacek L.J., George A.L. Jr., Griggs R.C., Tawil R., Kallen R.G.,
RA   Barchi R.L., Robertson M., Leppert M.F.;
RT   "Identification of a mutation in the gene causing hyperkalemic
RT   periodic paralysis.";
RL   Cell 67:1021-1027(1991).
RN   [9]
RP   VARIANT HYPP VAL-1592.
RX   PubMed=1659668; DOI=10.1038/354387a0;
RA   Rojas C.V., Wang J., Schwartz L.S., Hoffman E.P., Powell B.R.,
RA   Brown R.H. Jr.;
RT   "A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-
RT   subunit in hyperkalaemic periodic paralysis.";
RL   Nature 354:387-389(1991).
RN   [10]
RP   VARIANTS PMC PHE-804 AND THR-1156.
RX   PubMed=1338909; DOI=10.1038/ng1092-148;
RA   McClatchey A.I., McKenna-Yasek D., Cros D., Worthen H.G., Kuncl R.W.,
RA   Desilva S.M., Cornblath D.R., Gusella J.F., Brown R.H. Jr.;
RT   "Novel mutations in families with unusual and variable disorders of
RT   the skeletal muscle sodium channel.";
RL   Nat. Genet. 2:148-152(1992).
RN   [11]
RP   VARIANTS PMC CYS-1448 AND HIS-1448.
RX   PubMed=1316765; DOI=10.1016/0896-6273(92)90203-P;
RA   Ptacek L.J., George A.L. Jr., Barchi R.L., Griggs R.C., Riggs J.E.,
RA   Robertson M., Leppert M.F.;
RT   "Mutations in an S4 segment of the adult skeletal muscle sodium
RT   channel cause paramyotonia congenita.";
RL   Neuron 8:891-897(1992).
RN   [12]
RP   VARIANT PMC/HYPP ARG-1433.
RX   PubMed=8388676; DOI=10.1002/ana.410330312;
RA   Ptacek L.J., Gouw L., Kwiecinski H., McManis P., Mendell J.R.,
RA   Barohn R.J., George A.L. Jr., Barchi R.L., Robertson M., Leppert M.F.;
RT   "Sodium channel mutations in paramyotonia congenita and hyperkalemic
RT   periodic paralysis.";
RL   Ann. Neurol. 33:300-307(1993).
RN   [13]
RP   VARIANTS PMC ALA-1306; GLU-1306 AND VAL-1306.
RX   PubMed=8308722; DOI=10.1113/jphysiol.1993.sp019843;
RA   Lerche H., Heine R., Pika U., George A.L. Jr., Mitrovic N.,
RA   Browatzki M., Weiss T., Rivet-Bastide M., Franke C., Lomonaco M.,
RA   Ricker K., Lehmann-Horn F.;
RT   "Human sodium channel myotonia: slowed channel inactivation due to
RT   substitutions for a glycine within the III-IV linker.";
RL   J. Physiol. (Lond.) 470:13-22(1993).
RN   [14]
RP   VARIANT PMC MET-1589.
RX   PubMed=8242056; DOI=10.1093/hmg/2.9.1349;
RA   Heine R., Pika U., Lehmann-Horn F.;
RT   "A novel SCN4A mutation causing myotonia aggravated by cold and
RT   potassium.";
RL   Hum. Mol. Genet. 2:1349-1353(1993).
RN   [15]
RP   VARIANT MYOSCN4A VAL-1160.
RX   PubMed=8058156; DOI=10.1212/WNL.44.8.1500;
RA   Ptacek L.J., Tawil R., Griggs R.C., Meola G., McManis P., Barohn R.J.,
RA   Mendell J.R., Harris C., Spitzer R., Santiago F., Leppert M.F.;
RT   "Sodium channel mutations in acetazolamide-responsive myotonia
RT   congenita, paramyotonia congenita, and hyperkalemic periodic
RT   paralysis.";
RL   Neurology 44:1500-1503(1994).
RN   [16]
RP   VARIANT ILE-781.
RX   PubMed=7695243; DOI=10.1002/ana.410370320;
RA   Baquero J.L., Ayala R.A., Wang J., Curless R.G., Feero W.G.,
RA   Hoffman E.P., Ebeid M.R.;
RT   "Hyperkalemic periodic paralysis with cardiac dysrhythmia: a novel
RT   sodium channel mutation?";
RL   Ann. Neurol. 37:408-411(1995).
RN   [17]
RP   VARIANT PMC ILE-1293.
RX   PubMed=8580427;
RA   Koch M.C., Baumbach K., George A.L. Jr., Ricker K.;
RT   "Paramyotonia congenita without paralysis on exposure to cold: a novel
RT   mutation in the SCN4A gene (Val1293Ile).";
RL   NeuroReport 6:2001-2004(1995).
RN   [18]
RP   VARIANT ILE-781.
RX   PubMed=9266738; DOI=10.1002/ana.410420219;
RA   Green D.S., Hayward L.J., George A.L. Jr., Cannon S.C.;
RT   "A proposed mutation, Val781Ile, associated with hyperkalemic periodic
RT   paralysis and cardiac dysrhythmia is a benign polymorphism.";
RL   Ann. Neurol. 42:253-256(1997).
RN   [19]
RP   VARIANT MYOSCN4A MET-445.
RX   PubMed=9392583; DOI=10.1002/ana.410420520;
RA   Rosenfeld J., Sloan-Brown K., George A.L. Jr.;
RT   "A novel muscle sodium channel mutation causes painful congenital
RT   myotonia.";
RL   Ann. Neurol. 42:811-814(1997).
RN   [20]
RP   VARIANT PMC GLU-1456.
RX   PubMed=10369308; DOI=10.1001/archneur.56.6.692;
RA   Sasaki R., Takano H., Kamakura K., Kaida K., Hirata A., Saito M.,
RA   Tanaka H., Kuzuhara S., Tsuji S.;
RT   "A novel mutation in the gene for the adult skeletal muscle sodium
RT   channel alpha-subunit (SCN4A) that causes paramyotonia congenita of
RT   von Eulenburg.";
RL   Arch. Neurol. 56:692-696(1999).
RN   [21]
RP   VARIANT MYOSCN4A MET-445.
RX   PubMed=10218481; DOI=10.1016/S0014-5793(99)00338-5;
RA   Wang D.W., VanDeCarr D., Ruben P.C., George A.L. Jr., Bennett P.B.;
RT   "Functional consequences of a domain 1/S6 segment sodium channel
RT   mutation associated with painful congenital myotonia.";
RL   FEBS Lett. 448:231-234(1999).
RN   [22]
RP   VARIANT HOKPP2 HIS-669.
RX   PubMed=10599760; DOI=10.1212/WNL.53.9.1932;
RA   Bulman D.E., Scoggan K.A., van Oene M.D., Nicolle M.W., Hahn A.F.,
RA   Tollar L.L., Ebers G.C.;
RT   "A novel sodium channel mutation in a family with hypokalemic periodic
RT   paralysis.";
RL   Neurology 53:1932-1936(1999).
RN   [23]
RP   VARIANT PMC GLU-1456.
RX   PubMed=10727489; DOI=10.1136/jnnp.68.4.504;
RA   Davies N.P., Eunson L.H., Gregory R.P., Mills K.R., Morrison P.J.,
RA   Hanna M.G.;
RT   "Clinical, electrophysiological, and molecular genetic studies in a
RT   new family with paramyotonia congenita.";
RL   J. Neurol. Neurosurg. Psych. 68:504-507(2000).
RN   [24]
RP   VARIANT HOKPP2 SER-1158.
RX   PubMed=10851391; DOI=10.1212/WNL.54.11.2179;
RA   Sugiura Y., Aoki T., Sugiyama Y., Hida C., Ogata M., Yamamoto T.;
RT   "Temperature-sensitive sodium channelopathy with heat-induced myotonia
RT   and cold-induced paralysis.";
RL   Neurology 54:2179-2181(2000).
RN   [25]
RP   VARIANTS HOKPP2 GLY-672 AND HIS-672.
RX   PubMed=10944223; DOI=10.1073/pnas.97.17.9549;
RA   Jurkat-Rott K., Mitrovic N., Hang C., Kouzmekine A., Iaizzo P.,
RA   Herzog J., Lerche H., Nicole S., Vale-Santos J., Chauveau D.,
RA   Fontaine B., Lehmann-Horn F.;
RT   "Voltage-sensor sodium channel mutations cause hypokalemic periodic
RT   paralysis type 2 by enhanced inactivation and reduced current.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:9549-9554(2000).
RN   [26]
RP   VARIANT HOKPP2 SER-672.
RX   PubMed=11558801; DOI=10.1002/ana.1144;
RA   Bendahhou S., Cummins T.R., Griggs R.C., Fu Y.H., Ptacek L.J.;
RT   "Sodium channel inactivation defects are associated with
RT   acetazolamide-exacerbated hypokalemic periodic paralysis.";
RL   Ann. Neurol. 50:417-420(2001).
RN   [27]
RP   VARIANT HOKPP2 SER-672.
RX   PubMed=11591859; DOI=10.1212/WNL.57.7.1323;
RA   Davies N.P., Eunson L.H., Samuel M., Hanna M.G.;
RT   "Sodium channel gene mutations in hypokalemic periodic paralysis: an
RT   uncommon cause in the UK.";
RL   Neurology 57:1323-1325(2001).
RN   [28]
RP   VARIANTS PMC MET-1313 AND CYS-1448, CHARACTERIZATION OF VARIANTS PMC
RP   MET-1313 AND CYS-1448, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=15318338; DOI=10.1002/mus.20080;
RA   Dice M.S., Abbruzzese J.L., Wheeler J.T., Groome J.R., Fujimoto E.,
RA   Ruben P.C.;
RT   "Temperature-sensitive defects in paramyotonia congenita mutants
RT   R1448C and T1313M.";
RL   Muscle Nerve 30:277-288(2004).
RN   [29]
RP   VARIANTS NKPP GLY-675; GLN-675 AND TRP-675.
RX   PubMed=15596759; DOI=10.1212/01.WNL.0000145768.09934.EC;
RA   Vicart S., Sternberg D., Fournier E., Ochsner F., Laforet P.,
RA   Kuntzer T., Eymard B., Hainque B., Fontaine B.;
RT   "New mutations of SCN4A cause a potassium-sensitive normokalemic
RT   periodic paralysis.";
RL   Neurology 63:2120-2127(2004).
RN   [30]
RP   VARIANT PMC ASP-1152.
RX   PubMed=15790667; DOI=10.1113/jphysiol.2004.081018;
RA   Bouhours M., Luce S., Sternberg D., Willer J.-C., Fontaine B.,
RA   Tabti N.;
RT   "A1152D mutation of the Na+ channel causes paramyotonia congenita and
RT   emphasizes the role of DIII/S4-S5 linker in fast inactivation.";
RL   J. Physiol. (Lond.) 565:415-427(2005).
RN   [31]
RP   VARIANT PMC LYS-270, AND VARIANTS MYOSCN4A THR-715; ASN-804 AND
RP   ASN-1310.
RX   PubMed=16786525; DOI=10.1002/ana.20905;
RA   Fournier E., Viala K., Gervais H., Sternberg D., Arzel-Hezode M.,
RA   Laforet P., Eymard B., Tabti N., Willer J.-C., Vial C., Fontaine B.;
RT   "Cold extends electromyography distinction between ion channel
RT   mutations causing myotonia.";
RL   Ann. Neurol. 60:356-365(2006).
RN   [32]
RP   VARIANT HOKPP2 GLN-1132, CHARACTERIZATION OF VARIANT HOKPP2 GLN-1132,
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16890191; DOI=10.1016/j.bbrc.2006.07.101;
RA   Carle T., Lhuillier L., Luce S., Sternberg D., Devuyst O.,
RA   Fontaine B., Tabti N.;
RT   "Gating defects of a novel Na+ channel mutant causing hypokalemic
RT   periodic paralysis.";
RL   Biochem. Biophys. Res. Commun. 348:653-661(2006).
RN   [33]
RP   VARIANT MYOSCN4A GLU-1306.
RX   PubMed=16832098; DOI=10.1212/01.wnl.0000223838.88872.da;
RA   Colding-Joergensen E., Duno M., Vissing J.;
RT   "Autosomal dominant monosymptomatic myotonia permanens.";
RL   Neurology 67:153-155(2006).
RN   [34]
RP   VARIANTS HOKPP2 HIS-669; CYS-672 AND GLY-672.
RX   PubMed=18162704; DOI=10.3346/jkms.2007.22.6.946;
RA   Kim J.-B., Kim M.-H., Lee S.J., Kim D.-J., Lee B.C.;
RT   "The genotype and clinical phenotype of Korean patients with familial
RT   hypokalemic periodic paralysis.";
RL   J. Korean Med. Sci. 22:946-951(2007).
RN   [35]
RP   VARIANT MYOSCN4A ASP-1481.
RX   PubMed=17212350; DOI=10.1002/mus.20733;
RA   Schoser B.G.H., Schroeder J.M., Grimm T., Sternberg D., Kress W.;
RT   "A large German kindred with cold-aggravated myotonia and a
RT   heterozygous A1481D mutation in the SCN4A gene.";
RL   Muscle Nerve 35:599-606(2007).
RN   [36]
RP   VARIANT MYOSCN4A ILE-1476.
RX   PubMed=17998485; DOI=10.1212/01.wnl.0000290831.08585.2c;
RA   Rossignol E., Mathieu J., Thiffault I., Tetreault M., Dicaire M.J.,
RA   Chrestian N., Dupre N., Puymirat J., Brais B.;
RT   "A novel founder SCN4A mutation causes painful cold-induced myotonia
RT   in French-Canadians.";
RL   Neurology 69:1937-1941(2007).
RN   [37]
RP   VARIANT MYOSCN4A LYS-1297.
RX   PubMed=18203179; DOI=10.1002/ajmg.a.32141;
RA   Gay S., Dupuis D., Faivre L., Masurel-Paulet A., Labenne M.,
RA   Colombani M., Soichot P., Huet F., Hainque B., Sternberg D.,
RA   Fontaine B., Gouyon J.B., Thauvin-Robinet C.;
RT   "Severe neonatal non-dystrophic myotonia secondary to a novel mutation
RT   of the voltage-gated sodium channel (SCN4A) gene.";
RL   Am. J. Med. Genet. A 146:380-383(2008).
RN   [38]
RP   VARIANTS NKPP GLN-675 AND VAL-1592, AND VARIANT ILE-781.
RX   PubMed=18046642; DOI=10.1007/s10571-007-9231-4;
RA   Xiuhai G., Weiping W., Ke Z., Hongbin W., Yiling S., Yanling M.;
RT   "Mutations of sodium channel alpha-subunit genes in Chinese patients
RT   with normokalemic periodic paralysis.";
RL   Cell. Mol. Neurobiol. 28:653-661(2008).
RN   [39]
RP   CHARACTERIZATION OF VARIANTS PMC SER-1473 AND ILE-1705.
RX   PubMed=18690054; DOI=10.4161/chan.2.1.6051;
RA   Groome J.R., Larsen M.F., Coonts A.;
RT   "Differential effects of paramyotonia congenita mutations F1473S and
RT   F1705I on sodium channel gating.";
RL   Channels 2:39-50(2008).
RN   [40]
RP   VARIANTS PMC LYS-270; MET-704; ALA-1306; GLU-1306; MET-1313; PRO-1436;
RP   CYS-1448; HIS-1448; LEU-1448; GLU-1456; SER-1473 AND MET-1589.
RX   PubMed=18166706; DOI=10.1212/01.wnl.0000287069.21162.94;
RA   Matthews E., Tan S.V., Fialho D., Sweeney M.G., Sud R., Haworth A.,
RA   Stanley E., Cea G., Davis M.B., Hanna M.G.;
RT   "What causes paramyotonia in the United Kingdom? Common and new SCN4A
RT   mutations revealed.";
RL   Neurology 70:50-53(2008).
RN   [41]
RP   VARIANT HOKPP2 SER-1158, AND CHARACTERIZATION OF VARIANT HOKPP2
RP   SER-1158.
RX   PubMed=17898326; DOI=10.1212/01.wnl.0000265397.70057.d8;
RA   Webb J., Cannon S.C.;
RT   "Cold-induced defects of sodium channel gating in atypical periodic
RT   paralysis plus myotonia.";
RL   Neurology 70:755-761(2008).
RN   [42]
RP   VARIANT MYOSCN4A VAL-141, AND CHARACTERIZATION OF VARIANT MYOSCN4A
RP   VAL-141.
RX   PubMed=19015483; DOI=10.1212/01.wnl.0000335168.86248.55;
RA   Petitprez S., Tiab L., Chen L., Kappeler L., Rosler K.M.,
RA   Schorderet D., Abriel H., Burgunder J.M.;
RT   "A novel dominant mutation of the Nav1.4 alpha-subunit domain I
RT   leading to sodium channel myotonia.";
RL   Neurology 71:1669-1675(2008).
RN   [43]
RP   VARIANTS MYOSCN4A TRP-225; THR-1156 AND GLU-1306, VARIANT PMC THR-693,
RP   AND VARIANT HYPP THR-1156.
RX   PubMed=20076800; DOI=10.3988/jcn.2009.5.4.186;
RA   Lee S.C., Kim H.S., Park Y.E., Choi Y.C., Park K.H., Kim D.S.;
RT   "Clinical diversity of SCN4A-mutation-associated skeletal muscle
RT   sodium channelopathy.";
RL   J. Clin. Neurol. 5:186-191(2009).
RN   [44]
RP   VARIANT MYOSCN4A GLU-1633, AND CHARACTERIZATION OF VARIANT MYOSCN4A
RP   GLU-1633.
RX   PubMed=19347921; DOI=10.1002/mus.21155;
RA   Kubota T., Kinoshita M., Sasaki R., Aoike F., Takahashi M.P.,
RA   Sakoda S., Hirose K.;
RT   "New mutation of the Na channel in the severe form of potassium-
RT   aggravated myotonia.";
RL   Muscle Nerve 39:666-673(2009).
RN   [45]
RP   VARIANTS MYOSCN4A MET-445; LYS-452; SER-671; VAL-1306 AND ILE-1476.
RX   PubMed=18337100; DOI=10.1016/j.nmd.2008.01.007;
RA   Dupre N., Chrestian N., Bouchard J.-P., Rossignol E., Brunet D.,
RA   Sternberg D., Brais B., Mathieu J., Puymirat J.;
RT   "Clinical, electrophysiologic, and genetic study of non-dystrophic
RT   myotonia in French-Canadians.";
RL   Neuromuscul. Disord. 19:330-334(2009).
RN   [46]
RP   VARIANTS HOKPP2 TRP-222; CYS-672; GLY-672; HIS-672; SER-672; GLN-1132
RP   AND HIS-1135.
RX   PubMed=19118277; DOI=10.1212/01.wnl.0000342387.65477.46;
RA   Matthews E., Labrum R., Sweeney M.G., Sud R., Haworth A.,
RA   Chinnery P.F., Meola G., Schorge S., Kullmann D.M., Davis M.B.,
RA   Hanna M.G.;
RT   "Voltage sensor charge loss accounts for most cases of hypokalemic
RT   periodic paralysis.";
RL   Neurology 72:1544-1547(2009).
RN   [47]
RP   VARIANT PMC MET-704.
RX   PubMed=19077043; DOI=10.1111/j.1440-1789.2008.00985.x;
RA   Luan X., Chen B., Liu Y., Zheng R., Zhang W., Yuan Y.;
RT   "Tubular aggregates in paralysis periodica paramyotonica with T704M
RT   mutation of SCN4A.";
RL   Neuropathology 29:579-584(2009).
RN   [48]
RP   VARIANT NKPP GLN-1129, AND VARIANT HOKPP2 GLN-1129.
RX   PubMed=20522878; DOI=10.1136/jnnp.2009.177451;
RA   Hong D., Luan X., Chen B., Zheng R., Zhang W., Wang Z., Yuan Y.;
RT   "Both hypokalaemic and normokalaemic periodic paralysis in different
RT   members of a single family with novel R1129Q mutation in SCN4A gene.";
RL   J. Neurol. Neurosurg. Psych. 81:703-704(2010).
RN   [49]
RP   VARIANT HOKPP2 HIS-672.
RX   PubMed=21043388;
RA   Incecik F., Herguner M.O., Altunbasak S., Lehman-Horn F.;
RT   "Hypokalemic periodic paralysis due to the SCN4A R672H mutation in a
RT   Turkish family.";
RL   Turk. J. Pediatr. 52:409-410(2010).
RN   [50]
RP   VARIANTS HOKPP2 CYS-1135 AND HIS-1135, AND CHARACTERIZATION OF
RP   VARIANTS HOKPP2 CYS-1135 AND HIS-1135.
RX   PubMed=24549961; DOI=10.1093/brain/awu015;
RA   Groome J.R., Lehmann-Horn F., Fan C., Wolf M., Winston V., Merlini L.,
RA   Jurkat-Rott K.;
RT   "NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting
RT   IIIS4 movement during recovery.";
RL   Brain 137:998-1008(2014).
RN   [51]
RP   VARIANT CMS16 HIS-1457, AND CHARACTERIZATION OF VARIANT CMS16
RP   HIS-1457.
RX   PubMed=25707578; DOI=10.1002/ana.24389;
RA   Arnold W.D., Feldman D.H., Ramirez S., He L., Kassar D., Quick A.,
RA   Klassen T.L., Lara M., Nguyen J., Kissel J.T., Lossin C.,
RA   Maselli R.A.;
RT   "Defective fast inactivation recovery of Nav 1.4 in congenital
RT   myasthenic syndrome.";
RL   Ann. Neurol. 77:840-850(2015).
RN   [52]
RP   INVOLVEMENT IN FETAL HYPOKINESIA AND CONGENITAL MYOPATHY, VARIANTS
RP   HIS-104; LYS-203; TRP-225; THR-382; ASN-1069; CYS-1135 AND PHE-1209,
RP   AND CHARACTERIZATION OF VARIANTS HIS-104; LYS-203; TRP-225; THR-382;
RP   ASN-1069 AND PHE-1209.
RX   PubMed=26700687; DOI=10.1093/brain/awv352;
RA   Zaharieva I.T., Thor M.G., Oates E.C., van Karnebeek C., Hendson G.,
RA   Blom E., Witting N., Rasmussen M., Gabbett M.T., Ravenscroft G.,
RA   Sframeli M., Suetterlin K., Sarkozy A., D'Argenzio L., Hartley L.,
RA   Matthews E., Pitt M., Vissing J., Ballegaard M., Krarup C.,
RA   Sloerdahl A., Halvorsen H., Ye X.C., Zhang L.H., Loekken N.,
RA   Werlauff U., Abdelsayed M., Davis M.R., Feng L., Phadke R.,
RA   Sewry C.A., Morgan J.E., Laing N.G., Vallance H., Ruben P.,
RA   Hanna M.G., Lewis S., Kamsteeg E.J., Maennikkoe R., Muntoni F.;
RT   "Loss-of-function mutations in SCN4A cause severe foetal hypokinesia
RT   or 'classical' congenital myopathy.";
RL   Brain 139:674-691(2016).
RN   [53]
RP   VARIANT LEU-72, CHARACTERIZATION OF VARIANT LEU-72, AND INVOLVEMENT IN
RP   DM2.
RX   PubMed=25660391; DOI=10.1016/j.nmd.2015.01.006;
RA   Bugiardini E., Rivolta I., Binda A., Soriano Caminero A., Cirillo F.,
RA   Cinti A., Giovannoni R., Botta A., Cardani R., Wicklund M.P.,
RA   Meola G.;
RT   "SCN4A mutation as modifying factor of myotonic dystrophy type 2
RT   phenotype.";
RL   Neuromuscul. Disord. 25:301-307(2015).
RN   [54]
RP   VARIANT MYOSCN4A LEU-1290.
RX   PubMed=27653901; DOI=10.1016/j.jns.2016.08.030;
RA   Kato H., Kokunai Y., Dalle C., Kubota T., Madokoro Y., Yuasa H.,
RA   Uchida Y., Ikeda T., Mochizuki H., Nicole S., Fontaine B.,
RA   Takahashi M.P., Mitake S.;
RT   "A case of non-dystrophic myotonia with concomitant mutations in the
RT   SCN4A and CLCN1 genes.";
RL   J. Neurol. Sci. 369:254-258(2016).
RN   [55]
RP   VARIANT ILE-781.
RX   PubMed=27535533; DOI=10.1038/nature19057;
RG   Exome Aggregation Consortium;
RA   Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E.,
RA   Fennell T., O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B.,
RA   Tukiainen T., Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K.,
RA   Zhao F., Zou J., Pierce-Hoffman E., Berghout J., Cooper D.N.,
RA   Deflaux N., DePristo M., Do R., Flannick J., Fromer M., Gauthier L.,
RA   Goldstein J., Gupta N., Howrigan D., Kiezun A., Kurki M.I.,
RA   Moonshine A.L., Natarajan P., Orozco L., Peloso G.M., Poplin R.,
RA   Rivas M.A., Ruano-Rubio V., Rose S.A., Ruderfer D.M., Shakir K.,
RA   Stenson P.D., Stevens C., Thomas B.P., Tiao G., Tusie-Luna M.T.,
RA   Weisburd B., Won H.H., Yu D., Altshuler D.M., Ardissino D.,
RA   Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA   Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S.,
RA   Laakso M., McCarroll S., McCarthy M.I., McGovern D., McPherson R.,
RA   Neale B.M., Palotie A., Purcell S.M., Saleheen D., Scharf J.M.,
RA   Sklar P., Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C.,
RA   Wilson J.G., Daly M.J., MacArthur D.G.;
RT   "Analysis of protein-coding genetic variation in 60,706 humans.";
RL   Nature 536:285-291(2016).
RN   [56]
RP   VARIANT CMS16 TRP-1454, AND CHARACTERIZATION OF VARIANT CMS16
RP   TRP-1454.
RX   PubMed=26659129; DOI=10.1212/WNL.0000000000002264;
RA   Habbout K., Poulin H., Rivier F., Giuliano S., Sternberg D.,
RA   Fontaine B., Eymard B., Morales R.J., Echenne B., King L., Hanna M.G.,
RA   Maennikkoe R., Chahine M., Nicole S., Bendahhou S.;
RT   "A recessive Nav1.4 mutation underlies congenital myasthenic syndrome
RT   with periodic paralysis.";
RL   Neurology 86:161-169(2016).
CC   -!- FUNCTION: This protein mediates the voltage-dependent sodium ion
CC       permeability of excitable membranes. Assuming opened or closed
CC       conformations in response to the voltage difference across the
CC       membrane, the protein forms a sodium-selective channel through
CC       which Na(+) ions may pass in accordance with their electrochemical
CC       gradient. This sodium channel may be present in both denervated
CC       and innervated skeletal muscle. {ECO:0000269|PubMed:15318338,
CC       ECO:0000269|PubMed:16890191}.
CC   -!- SUBUNIT: Muscle sodium channels contain an alpha subunit and a
CC       smaller beta subunit. Heterooligomer with SCN2B or SCN4B;
CC       disulfide-linked. Interacts with the PDZ domain of the syntrophin
CC       SNTA1, SNTB1 and SNTB2. Interacts with the conotoxin GVIIJ
CC       (PubMed:24497506). {ECO:0000250|UniProtKB:P04775,
CC       ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:24497506}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15318338,
CC       ECO:0000269|PubMed:16890191}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:D0E0C2}.
CC   -!- DOMAIN: The sequence contains 4 internal repeats, each with 5
CC       hydrophobic segments (S1, S2, S3, S5, S6) and one positively
CC       charged segment (S4). Segments S4 are probably the voltage-sensors
CC       and are characterized by a series of positively charged amino
CC       acids at every third position. {ECO:0000305}.
CC   -!- PTM: Phosphorylation at Ser-1328 by PKC in a highly conserved
CC       cytoplasmic loop slows inactivation of the sodium channel and
CC       reduces peak sodium currents. {ECO:0000250}.
CC   -!- DISEASE: Paramyotonia congenita of von Eulenburg (PMC)
CC       [MIM:168300]: An autosomal dominant channelopathy characterized by
CC       myotonia, increased by exposure to cold, intermittent flaccid
CC       paresis, not necessarily dependent on cold or myotonia, lability
CC       of serum potassium, non-progressive nature and lack of atrophy or
CC       hypertrophy of muscles. In some patients, myotonia is not
CC       increased by cold exposure (paramyotonia without cold paralysis).
CC       Patients may have a combination phenotype of PMC and HYPP.
CC       {ECO:0000269|PubMed:10369308, ECO:0000269|PubMed:10727489,
CC       ECO:0000269|PubMed:1310898, ECO:0000269|PubMed:1316765,
CC       ECO:0000269|PubMed:1338909, ECO:0000269|PubMed:15318338,
CC       ECO:0000269|PubMed:15790667, ECO:0000269|PubMed:16786525,
CC       ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:18690054,
CC       ECO:0000269|PubMed:19077043, ECO:0000269|PubMed:20076800,
CC       ECO:0000269|PubMed:8242056, ECO:0000269|PubMed:8308722,
CC       ECO:0000269|PubMed:8388676, ECO:0000269|PubMed:8580427}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]:
CC       An autosomal dominant disorder manifested by episodic flaccid
CC       generalized muscle weakness associated with falls of serum
CC       potassium levels. {ECO:0000269|PubMed:10599760,
CC       ECO:0000269|PubMed:10851391, ECO:0000269|PubMed:10944223,
CC       ECO:0000269|PubMed:11558801, ECO:0000269|PubMed:11591859,
CC       ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326,
CC       ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277,
CC       ECO:0000269|PubMed:20522878, ECO:0000269|PubMed:21043388,
CC       ECO:0000269|PubMed:24549961}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An
CC       autosomal dominant channelopathy characterized by episodic flaccid
CC       generalized muscle weakness associated with high levels of serum
CC       potassium. Concurrence of myotonia is found in HYPP patients.
CC       {ECO:0000269|PubMed:1659668, ECO:0000269|PubMed:1659948,
CC       ECO:0000269|PubMed:20076800}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Periodic paralysis normokalemic (NKPP) [MIM:170500]: A
CC       disorder closely related to hyperkalemic periodic paralysis, but
CC       marked by a lack of alterations in potassium levels during attacks
CC       of muscle weakness. {ECO:0000269|PubMed:15596759,
CC       ECO:0000269|PubMed:18046642, ECO:0000269|PubMed:20522878}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A
CC       phenotypically highly variable myotonia aggravated by potassium
CC       loading, and sometimes by cold. Myotonia is characterized by
CC       sustained muscle tensing that prevents muscles from relaxing
CC       normally. It causes muscle stiffness that can interfere with
CC       movement. In some people the stiffness is very mild, while in
CC       other cases it may be severe enough to interfere with walking,
CC       running, and other activities of daily life. Myotonia SCN4A-
CC       related includes myotonia permanens and myotonia fluctuans. In
CC       myotonia permanens, the myotonia is generalized and there is a
CC       hypertrophy of the muscle, particularly in the neck and the
CC       shoulder. Attacks of severe muscle stiffness of the thoracic
CC       muscles may be life threatening due to impaired ventilation. In
CC       myotonia fluctuans, the muscle stiffness may fluctuate from day to
CC       day, provoked by exercise. {ECO:0000269|PubMed:10218481,
CC       ECO:0000269|PubMed:16786525, ECO:0000269|PubMed:16832098,
CC       ECO:0000269|PubMed:17212350, ECO:0000269|PubMed:17998485,
CC       ECO:0000269|PubMed:18203179, ECO:0000269|PubMed:18337100,
CC       ECO:0000269|PubMed:19015483, ECO:0000269|PubMed:19347921,
CC       ECO:0000269|PubMed:20076800, ECO:0000269|PubMed:27653901,
CC       ECO:0000269|PubMed:8058156, ECO:0000269|PubMed:9392583}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Myasthenic syndrome, congenital, 16 (CMS16) [MIM:614198]:
CC       A form of congenital myasthenic syndrome, a group of disorders
CC       characterized by failure of neuromuscular transmission, including
CC       pre-synaptic, synaptic, and post-synaptic disorders that are not
CC       of autoimmune origin. Clinical features are easy fatigability and
CC       muscle weakness. CMS16 is characterized by fatigable generalized
CC       weakness and recurrent attacks of respiratory and bulbar paralysis
CC       since birth. The fatigable weakness involves lid-elevator,
CC       external ocular, facial, limb and truncal muscles and an
CC       decremental response of the compound muscle action potential on
CC       repetitive stimulation. {ECO:0000269|PubMed:12766226,
CC       ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Note=SCN4A mutations are the cause of an autosomal
CC       recessive neuromuscular disorder characterized by severe fetal
CC       hypokinesia, neonatal hypotonia and congenital myopathy of
CC       variable severity. The most severe clinical features include
CC       reduced or absent fetal movements, in-utero upper and lower limb
CC       contractures, talipes and hydrops, and intrauterine or early
CC       postnatal death. Mildly affected patients present with generalized
CC       hypotonia and weakness at birth or within the first few days of
CC       life, mild-to-moderate facial muscle weakness without ptosis,
CC       significant early respiratory and feeding difficulties, and
CC       skeletal abnormalities of the spine and palate. Symptoms improve
CC       over time in patients who survive infancy, resulting in gain of
CC       muscle strength and motor skills and concomitant resolution of
CC       early respiratory and feeding difficulties. In contrast to other
CC       SCN4A-related channelopathies, affected individuals manifest in-
CC       utero or neonatal onset of permanent muscle weakness, rather than
CC       later-onset episodic muscle weakness.
CC       {ECO:0000269|PubMed:26700687}.
CC   -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC       Nav1.4/SCN4A subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=SCN4A entry;
CC       URL="https://en.wikipedia.org/wiki/SCN4A";
DR   EMBL; M81758; AAA60554.1; -; mRNA.
DR   EMBL; L04236; AAB59624.1; -; Genomic_DNA.
DR   EMBL; L04216; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04217; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04218; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04219; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04220; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04221; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04222; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04223; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04224; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04225; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04226; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04227; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04228; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04229; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04230; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04231; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04232; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04233; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04234; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; L04235; AAB59624.1; JOINED; Genomic_DNA.
DR   EMBL; AY212253; AAO83647.1; -; mRNA.
DR   EMBL; L01983; AAA75557.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; L01962; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01963; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01964; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01965; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01966; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01967; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01968; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01969; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01970; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01971; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01972; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01973; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01974; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01975; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01976; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01977; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01978; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01979; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01980; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01981; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; L01982; AAA75557.1; JOINED; Genomic_DNA.
DR   EMBL; AC127029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; S82622; AAB21450.2; -; Genomic_DNA.
DR   CCDS; CCDS45761.1; -.
DR   PIR; I51964; I51964.
DR   PIR; I54323; I54323.
DR   PIR; I64893; I64893.
DR   PIR; JS0648; JS0648.
DR   RefSeq; NP_000325.4; NM_000334.4.
DR   UniGene; Hs.46038; -.
DR   ProteinModelPortal; P35499; -.
DR   SMR; P35499; -.
DR   BioGrid; 112234; 4.
DR   STRING; 9606.ENSP00000396320; -.
DR   BindingDB; P35499; -.
DR   ChEMBL; CHEMBL2072; -.
DR   DrugBank; DB00586; Diclofenac.
DR   DrugBank; DB01195; Flecainide.
DR   DrugBank; DB00818; Propofol.
DR   DrugBank; DB00313; Valproic Acid.
DR   DrugBank; DB00909; Zonisamide.
DR   GuidetoPHARMACOLOGY; 581; -.
DR   TCDB; 1.A.1.10.4; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; P35499; -.
DR   PhosphoSitePlus; P35499; -.
DR   BioMuta; SCN4A; -.
DR   DMDM; 292495096; -.
DR   PaxDb; P35499; -.
DR   PeptideAtlas; P35499; -.
DR   PRIDE; P35499; -.
DR   DNASU; 6329; -.
DR   Ensembl; ENST00000435607; ENSP00000396320; ENSG00000007314.
DR   GeneID; 6329; -.
DR   KEGG; hsa:6329; -.
DR   UCSC; uc002jds.1; human.
DR   CTD; 6329; -.
DR   DisGeNET; 6329; -.
DR   EuPathDB; HostDB:ENSG00000007314.11; -.
DR   GeneCards; SCN4A; -.
DR   GeneReviews; SCN4A; -.
DR   H-InvDB; HIX0039131; -.
DR   HGNC; HGNC:10591; SCN4A.
DR   HPA; HPA053992; -.
DR   MalaCards; SCN4A; -.
DR   MIM; 168300; phenotype.
DR   MIM; 170500; phenotype.
DR   MIM; 603967; gene.
DR   MIM; 608390; phenotype.
DR   MIM; 613345; phenotype.
DR   MIM; 614198; phenotype.
DR   neXtProt; NX_P35499; -.
DR   OpenTargets; ENSG00000007314; -.
DR   Orphanet; 99736; Acetazolamide-responsive myotonia.
DR   Orphanet; 682; Hyperkalemic periodic paralysis.
DR   Orphanet; 681; Hypokalemic periodic paralysis.
DR   Orphanet; 99734; Myotonia fluctuans.
DR   Orphanet; 99735; Myotonia permanens.
DR   Orphanet; 684; Paramyotonia congenita of Von Eulenburg.
DR   Orphanet; 98913; Postsynaptic congenital myasthenic syndromes.
DR   PharmGKB; PA35006; -.
DR   eggNOG; ENOG410INF8; Eukaryota.
DR   eggNOG; COG1226; LUCA.
DR   GeneTree; ENSGT00830000128242; -.
DR   HOGENOM; HOG000231755; -.
DR   HOVERGEN; HBG053100; -.
DR   InParanoid; P35499; -.
DR   KO; K04837; -.
DR   OrthoDB; EOG091G00FK; -.
DR   PhylomeDB; P35499; -.
DR   TreeFam; TF323985; -.
DR   Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR   Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR   SIGNOR; P35499; -.
DR   ChiTaRS; SCN4A; human.
DR   GeneWiki; Nav1.4; -.
DR   GenomeRNAi; 6329; -.
DR   PRO; PR:P35499; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   Bgee; ENSG00000007314; -.
DR   CleanEx; HS_SCN4A; -.
DR   Genevisible; P35499; HS.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0001518; C:voltage-gated sodium channel complex; IEA:InterPro.
DR   GO; GO:0005248; F:voltage-gated sodium channel activity; IBA:GO_Central.
DR   GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR   GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR   GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR   GO; GO:0006814; P:sodium ion transport; TAS:ProtInc.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR   InterPro; IPR008052; Na_channel_a4su_mammal.
DR   InterPro; IPR001696; Na_channel_asu.
DR   InterPro; IPR010526; Na_trans_assoc.
DR   Pfam; PF00520; Ion_trans; 4.
DR   Pfam; PF06512; Na_trans_assoc; 1.
DR   PRINTS; PR00170; NACHANNEL.
DR   PRINTS; PR01665; NACHANNEL4.
DR   PROSITE; PS50096; IQ; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Complete proteome; Congenital myasthenic syndrome;
KW   Disease mutation; Disulfide bond; Glycoprotein; Ion channel;
KW   Ion transport; Membrane; Phosphoprotein; Polymorphism;
KW   Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport;
KW   Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN         1   1836       Sodium channel protein type 4 subunit
FT                                alpha.
FT                                /FTId=PRO_0000048495.
FT   TOPO_DOM      1    131       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    132    150       Helical; Name=S1 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    151    157       Extracellular. {ECO:0000305}.
FT   TRANSMEM    158    178       Helical; Name=S2 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    179    192       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    193    210       Helical; Name=S3 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    211    216       Extracellular. {ECO:0000305}.
FT   TRANSMEM    217    233       Helical; Name=S4 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    234    252       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    253    272       Helical; Name=S5 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    273    391       Extracellular. {ECO:0000305}.
FT   INTRAMEM    392    416       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    417    423       Extracellular. {ECO:0000305}.
FT   TRANSMEM    424    444       Helical; Name=S6 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    445    578       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    579    597       Helical; Name=S1 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    598    608       Extracellular. {ECO:0000305}.
FT   TRANSMEM    609    628       Helical; Name=S2 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    629    642       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    643    662       Helical; Name=S3 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    663    664       Extracellular. {ECO:0000305}.
FT   TRANSMEM    665    682       Helical; Name=S4 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    683    698       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    699    717       Helical; Name=S5 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    718    746       Extracellular. {ECO:0000305}.
FT   INTRAMEM    747    767       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    768    780       Extracellular. {ECO:0000305}.
FT   TRANSMEM    781    801       Helical; Name=S6 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    802   1032       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1033   1050       Helical; Name=S1 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1051   1063       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1064   1082       Helical; Name=S2 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1083   1096       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1097   1115       Helical; Name=S3 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1116   1123       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1124   1142       Helical; Name=S4 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1143   1159       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1160   1179       Helical; Name=S5 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1180   1230       Extracellular. {ECO:0000305}.
FT   INTRAMEM   1231   1252       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1253   1269       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1270   1291       Helical; Name=S6 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1292   1354       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1355   1372       Helical; Name=S1 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1373   1383       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1384   1402       Helical; Name=S2 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1403   1414       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1415   1432       Helical; Name=S3 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1433   1445       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1446   1462       Helical; Name=S4 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1463   1481       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1482   1499       Helical; Name=S5 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1500   1521       Extracellular. {ECO:0000305}.
FT   INTRAMEM   1522   1544       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1545   1574       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1575   1597       Helical; Name=S6 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1598   1836       Cytoplasmic. {ECO:0000305}.
FT   REPEAT      113    454       I. {ECO:0000305}.
FT   REPEAT      560    832       II. {ECO:0000305}.
FT   REPEAT     1013   1326       III. {ECO:0000305}.
FT   REPEAT     1335   1633       IV. {ECO:0000305}.
FT   DOMAIN     1727   1756       IQ. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00116}.
FT   MOD_RES    1328   1328       Phosphoserine; by PKC. {ECO:0000250}.
FT   CARBOHYD    214    214       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    288    288       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    291    291       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    297    297       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    303    303       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    315    315       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    321    321       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    333    333       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    362    362       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1191   1191       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1205   1205       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    280    369       {ECO:0000250|UniProtKB:D0E0C2}.
FT   DISULFID    729    729       Interchain; with SCN2B or SCN4B.
FT                                {ECO:0000250|UniProtKB:P04775}.
FT   DISULFID    729    729       Interchain; with the conotoxin GVIIJ
FT                                (when the channel is not linked to SCN2B
FT                                or SCN4B; the bond to SCN2B or SCN4B
FT                                protects the channel from the inhibition
FT                                by toxin).
FT                                {ECO:0000250|UniProtKB:P04775}.
FT   DISULFID    769    778       {ECO:0000250|UniProtKB:D0E0C2}.
FT   VARIANT      72     72       P -> L (found in a patient with severe
FT                                dystrophia myotonica 2 (DM2) carrying a
FT                                pathogenic CCTG repeat expansion in CNBP;
FT                                unknown pathological significance; may
FT                                act as a disease modifier; changes the
FT                                voltage-gated sodium channel activity;
FT                                increases membrane hyperexcitability;
FT                                decreases channel fast inactivation).
FT                                {ECO:0000269|PubMed:25660391}.
FT                                /FTId=VAR_074598.
FT   VARIANT     104    104       R -> H (probable disease-associated
FT                                mutation found in patients with severe
FT                                fetal hypokinesia or congenital myopathy;
FT                                complete loss of sodium channel
FT                                function). {ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_075430.
FT   VARIANT     135    135       M -> V.
FT                                /FTId=VAR_001560.
FT   VARIANT     141    141       I -> V (in MYOSCN4A; causes a
FT                                hyperpolarizing shift of the activation
FT                                curve; enhances channel slow
FT                                inactivation; dbSNP:rs121908561).
FT                                {ECO:0000269|PubMed:19015483}.
FT                                /FTId=VAR_054934.
FT   VARIANT     203    203       M -> K (probable disease-associated
FT                                mutation found in patients with severe
FT                                fetal hypokinesia or congenital myopathy;
FT                                impaired sodium channel function).
FT                                {ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_075431.
FT   VARIANT     222    222       R -> W (in HOKPP2; dbSNP:rs527236148).
FT                                {ECO:0000269|PubMed:19118277}.
FT                                /FTId=VAR_054935.
FT   VARIANT     225    225       R -> W (in MYOSCN4A; also found in
FT                                patients with severe fetal hypokinesia or
FT                                congenital myopathy; impaired sodium
FT                                channel function; dbSNP:rs764718003).
FT                                {ECO:0000269|PubMed:20076800,
FT                                ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_065230.
FT   VARIANT     246    246       S -> L (in dbSNP:rs80338951).
FT                                {ECO:0000269|PubMed:12766226}.
FT                                /FTId=VAR_017785.
FT   VARIANT     270    270       Q -> K (in PMC).
FT                                {ECO:0000269|PubMed:16786525,
FT                                ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_054936.
FT   VARIANT     382    382       P -> T (probable disease-associated
FT                                mutation found in patients with severe
FT                                fetal hypokinesia or congenital myopathy;
FT                                complete loss of sodium channel
FT                                function). {ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_075432.
FT   VARIANT     445    445       V -> M (in MYOSCN4A; dbSNP:rs121908552).
FT                                {ECO:0000269|PubMed:10218481,
FT                                ECO:0000269|PubMed:18337100,
FT                                ECO:0000269|PubMed:9392583}.
FT                                /FTId=VAR_017786.
FT   VARIANT     452    452       E -> K (in MYOSCN4A; variable phenotype
FT                                ranging from mild to severe myotonia;
FT                                dbSNP:rs372631097).
FT                                {ECO:0000269|PubMed:18337100}.
FT                                /FTId=VAR_054937.
FT   VARIANT     524    524       S -> G (in dbSNP:rs6504191).
FT                                {ECO:0000269|PubMed:12766226,
FT                                ECO:0000269|PubMed:1315496,
FT                                ECO:0000269|PubMed:1339144}.
FT                                /FTId=VAR_001561.
FT   VARIANT     559    559       N -> D (in dbSNP:rs1047705).
FT                                {ECO:0000269|PubMed:12766226,
FT                                ECO:0000269|PubMed:1315496}.
FT                                /FTId=VAR_017787.
FT   VARIANT     669    669       R -> H (in HOKPP2; dbSNP:rs80338784).
FT                                {ECO:0000269|PubMed:10599760,
FT                                ECO:0000269|PubMed:18162704}.
FT                                /FTId=VAR_017788.
FT   VARIANT     671    671       F -> S (in MYOSCN4A).
FT                                {ECO:0000269|PubMed:18337100}.
FT                                /FTId=VAR_054938.
FT   VARIANT     672    672       R -> C (in HOKPP2; dbSNP:rs80338785).
FT                                {ECO:0000269|PubMed:18162704,
FT                                ECO:0000269|PubMed:19118277}.
FT                                /FTId=VAR_054939.
FT   VARIANT     672    672       R -> G (in HOKPP2; dbSNP:rs80338785).
FT                                {ECO:0000269|PubMed:10944223,
FT                                ECO:0000269|PubMed:18162704,
FT                                ECO:0000269|PubMed:19118277}.
FT                                /FTId=VAR_017789.
FT   VARIANT     672    672       R -> H (in HOKPP2; dbSNP:rs80338788).
FT                                {ECO:0000269|PubMed:10944223,
FT                                ECO:0000269|PubMed:19118277,
FT                                ECO:0000269|PubMed:21043388}.
FT                                /FTId=VAR_017790.
FT   VARIANT     672    672       R -> S (in HOKPP2; dbSNP:rs80338785).
FT                                {ECO:0000269|PubMed:11558801,
FT                                ECO:0000269|PubMed:11591859,
FT                                ECO:0000269|PubMed:19118277}.
FT                                /FTId=VAR_017791.
FT   VARIANT     675    675       R -> G (in NKPP; dbSNP:rs121908556).
FT                                {ECO:0000269|PubMed:15596759}.
FT                                /FTId=VAR_037104.
FT   VARIANT     675    675       R -> Q (in NKPP; dbSNP:rs121908557).
FT                                {ECO:0000269|PubMed:15596759,
FT                                ECO:0000269|PubMed:18046642}.
FT                                /FTId=VAR_037105.
FT   VARIANT     675    675       R -> W (in NKPP; dbSNP:rs121908556).
FT                                {ECO:0000269|PubMed:15596759}.
FT                                /FTId=VAR_037106.
FT   VARIANT     693    693       I -> T (in PMC; dbSNP:rs80338956).
FT                                {ECO:0000269|PubMed:20076800}.
FT                                /FTId=VAR_065231.
FT   VARIANT     704    704       T -> M (in HYPP and PMC;
FT                                dbSNP:rs80338957).
FT                                {ECO:0000269|PubMed:1659948,
FT                                ECO:0000269|PubMed:18166706,
FT                                ECO:0000269|PubMed:19077043}.
FT                                /FTId=VAR_001562.
FT   VARIANT     715    715       A -> T (in MYOSCN4A; dbSNP:rs749400108).
FT                                {ECO:0000269|PubMed:16786525}.
FT                                /FTId=VAR_054940.
FT   VARIANT     781    781       V -> I (polymorphism; voltage-gated
FT                                sodium channel activity is not affected
FT                                and channel activation as well as fast
FT                                and slow inactivation curves are normal;
FT                                dbSNP:rs62070884).
FT                                {ECO:0000269|PubMed:18046642,
FT                                ECO:0000269|PubMed:27535533,
FT                                ECO:0000269|PubMed:7695243,
FT                                ECO:0000269|PubMed:9266738}.
FT                                /FTId=VAR_054941.
FT   VARIANT     804    804       S -> F (in PMC; dbSNP:rs121908546).
FT                                {ECO:0000269|PubMed:1338909}.
FT                                /FTId=VAR_001563.
FT   VARIANT     804    804       S -> N (in MYOSCN4A).
FT                                {ECO:0000269|PubMed:16786525}.
FT                                /FTId=VAR_054942.
FT   VARIANT     861    861       A -> D.
FT                                /FTId=VAR_001564.
FT   VARIANT    1069   1069       D -> N (probable disease-associated
FT                                mutation found in patients with severe
FT                                fetal hypokinesia or congenital myopathy;
FT                                impaired sodium channel function;
FT                                dbSNP:rs373150395).
FT                                {ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_075433.
FT   VARIANT    1129   1129       R -> Q (in NKPP and HOKPP2; detected in a
FT                                family where three affected members
FT                                manifested hypokalemic periodic paralysis
FT                                whereas five other patients had
FT                                normokalemic periodic paralysis;
FT                                dbSNP:rs527236149).
FT                                {ECO:0000269|PubMed:20522878}.
FT                                /FTId=VAR_064987.
FT   VARIANT    1132   1132       R -> Q (in HOKPP2; changes the voltage-
FT                                gated sodium channel activity; increases
FT                                membrane hypoexcitability; increases
FT                                channel activation and both fast and slow
FT                                channel inactivation; dbSNP:rs80338789).
FT                                {ECO:0000269|PubMed:16890191,
FT                                ECO:0000269|PubMed:19118277}.
FT                                /FTId=VAR_054943.
FT   VARIANT    1135   1135       R -> C (in HOKPP2; also found in patients
FT                                with severe fetal hypokinesia or
FT                                congenital myopathy; increased
FT                                depolarization tendency at normal and
FT                                reduced extracellular potassium and
FT                                reduced amplitude and rise time of action
FT                                potentials).
FT                                {ECO:0000269|PubMed:24549961,
FT                                ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_075434.
FT   VARIANT    1135   1135       R -> H (in HOKPP2; increased
FT                                depolarization tendency at normal and
FT                                reduced extracellular potassium and
FT                                reduced amplitude and rise time of action
FT                                potentials; dbSNP:rs527236150).
FT                                {ECO:0000269|PubMed:19118277,
FT                                ECO:0000269|PubMed:24549961}.
FT                                /FTId=VAR_054944.
FT   VARIANT    1152   1152       A -> D (in PMC).
FT                                {ECO:0000269|PubMed:15790667}.
FT                                /FTId=VAR_022341.
FT   VARIANT    1156   1156       A -> T (in PMC, MYOSCN4A and HYPP;
FT                                dbSNP:rs80338958).
FT                                {ECO:0000269|PubMed:1338909,
FT                                ECO:0000269|PubMed:20076800}.
FT                                /FTId=VAR_001565.
FT   VARIANT    1158   1158       P -> S (in HOKPP2; atypical phenotype
FT                                with heat-induced myotonia and cold-
FT                                induced paralysis with hypokalemia;
FT                                changes the voltage-gated sodium channel
FT                                activity; increases channel activation
FT                                and slow inactivation at low temperature;
FT                                dbSNP:rs121908555).
FT                                {ECO:0000269|PubMed:10851391,
FT                                ECO:0000269|PubMed:17898326}.
FT                                /FTId=VAR_017792.
FT   VARIANT    1160   1160       I -> V (in MYOSCN4A; acetazolamide-
FT                                responsive myotonia; dbSNP:rs121908549).
FT                                {ECO:0000269|PubMed:8058156}.
FT                                /FTId=VAR_017793.
FT   VARIANT    1209   1209       C -> F (probable disease-associated
FT                                mutation found in patients with severe
FT                                fetal hypokinesia or congenital myopathy;
FT                                complete loss of sodium channel
FT                                function). {ECO:0000269|PubMed:26700687}.
FT                                /FTId=VAR_075435.
FT   VARIANT    1290   1290       F -> L (in MYOSCN4A; enhances voltage-
FT                                gated sodium channel activation inducing
FT                                membrane hyperexcitability).
FT                                {ECO:0000269|PubMed:27653901}.
FT                                /FTId=VAR_079519.
FT   VARIANT    1293   1293       V -> I (in PMC; without cold paralysis;
FT                                dbSNP:rs121908551).
FT                                {ECO:0000269|PubMed:8580427}.
FT                                /FTId=VAR_001566.
FT   VARIANT    1297   1297       N -> K (in MYOSCN4A; unusually severe and
FT                                lethal phenotype with neonatal onset;
FT                                dbSNP:rs121908560).
FT                                {ECO:0000269|PubMed:18203179}.
FT                                /FTId=VAR_054945.
FT   VARIANT    1306   1306       G -> A (in PMC; dbSNP:rs80338792).
FT                                {ECO:0000269|PubMed:18166706,
FT                                ECO:0000269|PubMed:8308722}.
FT                                /FTId=VAR_001567.
FT   VARIANT    1306   1306       G -> E (in MYOSCN4A and PMC; severe;
FT                                dbSNP:rs80338792).
FT                                {ECO:0000269|PubMed:16832098,
FT                                ECO:0000269|PubMed:18166706,
FT                                ECO:0000269|PubMed:20076800,
FT                                ECO:0000269|PubMed:8308722}.
FT                                /FTId=VAR_001568.
FT   VARIANT    1306   1306       G -> V (in MYOSCN4A and PMC;
FT                                dbSNP:rs80338792).
FT                                {ECO:0000269|PubMed:1310898,
FT                                ECO:0000269|PubMed:18337100,
FT                                ECO:0000269|PubMed:8308722}.
FT                                /FTId=VAR_001569.
FT   VARIANT    1310   1310       I -> N (in MYOSCN4A).
FT                                {ECO:0000269|PubMed:16786525}.
FT                                /FTId=VAR_054946.
FT   VARIANT    1313   1313       T -> M (in PMC; changes the voltage-gated
FT                                sodium channel activity; increases
FT                                membrane hyperexcitability at low
FT                                temperature; decreases channel
FT                                activation, deactivation, fast
FT                                inactivation and recovery delay from fast
FT                                inactivation; dbSNP:rs121908547).
FT                                {ECO:0000269|PubMed:1310898,
FT                                ECO:0000269|PubMed:15318338,
FT                                ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_001570.
FT   VARIANT    1376   1376       N -> D (in dbSNP:rs2058194).
FT                                {ECO:0000269|PubMed:1315496}.
FT                                /FTId=VAR_017794.
FT   VARIANT    1433   1433       L -> R (in PMC and HYPP;
FT                                dbSNP:rs121908550).
FT                                {ECO:0000269|PubMed:8388676}.
FT                                /FTId=VAR_001571.
FT   VARIANT    1436   1436       L -> P (in PMC).
FT                                {ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_054947.
FT   VARIANT    1442   1442       V -> E (in CMS16; dbSNP:rs121908553).
FT                                {ECO:0000269|PubMed:12766226}.
FT                                /FTId=VAR_017795.
FT   VARIANT    1448   1448       R -> C (in PMC; changes the voltage-gated
FT                                sodium channel activity; increases
FT                                membrane hyperexcitability at low
FT                                temperature; decreases channel
FT                                activation, deactivation, fast
FT                                inactivation and recovery delay from fast
FT                                inactivation; dbSNP:rs121908544).
FT                                {ECO:0000269|PubMed:1316765,
FT                                ECO:0000269|PubMed:15318338,
FT                                ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_001572.
FT   VARIANT    1448   1448       R -> H (in PMC; dbSNP:rs121908545).
FT                                {ECO:0000269|PubMed:1316765,
FT                                ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_001573.
FT   VARIANT    1448   1448       R -> L (in PMC).
FT                                {ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_054948.
FT   VARIANT    1454   1454       R -> W (in CMS16; leads to
FT                                hyperpolarization of the steady-state
FT                                fast inactivation, slow recovery from
FT                                inactivation and reduces the channel
FT                                ability to activate in response to
FT                                repetitive stimulating pulses;
FT                                dbSNP:rs879253789).
FT                                {ECO:0000269|PubMed:26659129}.
FT                                /FTId=VAR_075436.
FT   VARIANT    1456   1456       G -> E (in PMC; dbSNP:rs121908554).
FT                                {ECO:0000269|PubMed:10369308,
FT                                ECO:0000269|PubMed:10727489,
FT                                ECO:0000269|PubMed:18166706}.
FT                                /FTId=VAR_037107.
FT   VARIANT    1457   1457       R -> H (in CMS16; enhanced fast
FT                                inactivation and slowed recovery from
FT                                fast inactivation; dbSNP:rs863225046).
FT                                {ECO:0000269|PubMed:25707578}.
FT                                /FTId=VAR_075437.
FT   VARIANT    1473   1473       F -> S (in PMC; accelerates deactivation
FT                                from the inactivated state and enhances
FT                                the remobilization of gating charge).
FT                                {ECO:0000269|PubMed:18166706,
FT                                ECO:0000269|PubMed:18690054}.
FT                                /FTId=VAR_054949.
FT   VARIANT    1476   1476       M -> I (in MYOSCN4A; highly variable
FT                                severity; dbSNP:rs121908559).
FT                                {ECO:0000269|PubMed:17998485,
FT                                ECO:0000269|PubMed:18337100}.
FT                                /FTId=VAR_054950.
FT   VARIANT    1481   1481       A -> D (in MYOSCN4A; fluctuating cold-
FT                                induced and exercise-induced stiffness).
FT                                {ECO:0000269|PubMed:17212350}.
FT                                /FTId=VAR_054951.
FT   VARIANT    1589   1589       V -> M (in PMC; dbSNP:rs121908548).
FT                                {ECO:0000269|PubMed:18166706,
FT                                ECO:0000269|PubMed:8242056}.
FT                                /FTId=VAR_001574.
FT   VARIANT    1592   1592       M -> V (in HYPP and NKPP;
FT                                dbSNP:rs80338962).
FT                                {ECO:0000269|PubMed:1659668,
FT                                ECO:0000269|PubMed:18046642}.
FT                                /FTId=VAR_001575.
FT   VARIANT    1633   1633       Q -> E (in MYOSCN4A; changes the voltage-
FT                                gated sodium channel activity; increases
FT                                membrane hyperexcitability; decreases
FT                                channel fast inactivation).
FT                                {ECO:0000269|PubMed:19347921}.
FT                                /FTId=VAR_074581.
FT   VARIANT    1705   1705       F -> I (in PMC; increases the extent of
FT                                charge immobilization in response to
FT                                strong depolarization).
FT                                {ECO:0000269|PubMed:18690054}.
FT                                /FTId=VAR_054952.
FT   CONFLICT     10     11       VP -> AR (in Ref. 1; AAA60554).
FT                                {ECO:0000305}.
FT   CONFLICT    371    371       E -> K (in Ref. 1; AAA60554).
FT                                {ECO:0000305}.
FT   CONFLICT    371    371       E -> Q (in Ref. 1; AAB59624).
FT                                {ECO:0000305}.
FT   CONFLICT    870    870       A -> G (in Ref. 1; AAB59624).
FT                                {ECO:0000305}.
FT   CONFLICT   1151   1152       NA -> KP (in Ref. 1; AAB59624).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1836 AA;  208061 MW;  FA9A6B81B7C2D50F CRC64;
     MARPSLCTLV PLGPECLRPF TRESLAAIEQ RAVEEEARLQ RNKQMEIEEP ERKPRSDLEA
     GKNLPMIYGD PPPEVIGIPL EDLDPYYSNK KTFIVLNKGK AIFRFSATPA LYLLSPFSVV
     RRGAIKVLIH ALFSMFIMIT ILTNCVFMTM SDPPPWSKNV EYTFTGIYTF ESLIKILARG
     FCVDDFTFLR DPWNWLDFSV IMMAYLTEFV DLGNISALRT FRVLRALKTI TVIPGLKTIV
     GALIQSVKKL SDVMILTVFC LSVFALVGLQ LFMGNLRQKC VRWPPPFNDT NTTWYSNDTW
     YGNDTWYGNE MWYGNDSWYA NDTWNSHASW ATNDTFDWDA YISDEGNFYF LEGSNDALLC
     GNSSDAGHCP EGYECIKTGR NPNYGYTSYD TFSWAFLALF RLMTQDYWEN LFQLTLRAAG
     KTYMIFFVVI IFLGSFYLIN LILAVVAMAY AEQNEATLAE DKEKEEEFQQ MLEKFKKHQE
     ELEKAKAAQA LEGGEADGDP AHGKDCNGSL DTSQGEKGAP RQSSSGDSGI SDAMEELEEA
     HQKCPPWWYK CAHKVLIWNC CAPWLKFKNI IHLIVMDPFV DLGITICIVL NTLFMAMEHY
     PMTEHFDNVL TVGNLVFTGI FTAEMVLKLI AMDPYEYFQQ GWNIFDSIIV TLSLVELGLA
     NVQGLSVLRS FRLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII VFIFAVVGMQ
     LFGKSYKECV CKIALDCNLP RWHMHDFFHS FLIVFRILCG EWIETMWDCM EVAGQAMCLT
     VFLMVMVIGN LVVLNLFLAL LLSSFSADSL AASDEDGEMN NLQIAIGRIK LGIGFAKAFL
     LGLLHGKILS PKDIMLSLGE ADGAGEAGEA GETAPEDEKK EPPEEDLKKD NHILNHMGLA
     DGPPSSLELD HLNFINNPYL TIQVPIASEE SDLEMPTEEE TDTFSEPEDS KKPPQPLYDG
     NSSVCSTADY KPPEEDPEEQ AEENPEGEQP EECFTEACVQ RWPCLYVDIS QGRGKKWWTL
     RRACFKIVEH NWFETFIVFM ILLSSGALAF EDIYIEQRRV IRTILEYADK VFTYIFIMEM
     LLKWVAYGFK VYFTNAWCWL DFLIVDVSII SLVANWLGYS ELGPIKSLRT LRALRPLRAL
     SRFEGMRVVV NALLGAIPSI MNVLLVCLIF WLIFSIMGVN LFAGKFYYCI NTTTSERFDI
     SEVNNKSECE SLMHTGQVRW LNVKVNYDNV GLGYLSLLQV ATFKGWMDIM YAAVDSREKE
     EQPQYEVNLY MYLYFVIFII FGSFFTLNLF IGVIIDNFNQ QKKKLGGKDI FMTEEQKKYY
     NAMKKLGSKK PQKPIPRPQN KIQGMVYDLV TKQAFDITIM ILICLNMVTM MVETDNQSQL
     KVDILYNINM IFIIIFTGEC VLKMLALRQY YFTVGWNIFD FVVVILSIVG LALSDLIQKY
     FVSPTLFRVI RLARIGRVLR LIRGAKGIRT LLFALMMSLP ALFNIGLLLF LVMFIYSIFG
     MSNFAYVKKE SGIDDMFNFE TFGNSIICLF EITTSAGWDG LLNPILNSGP PDCDPNLENP
     GTSVKGDCGN PSIGICFFCS YIIISFLIVV NMYIAIILEN FNVATEESSE PLGEDDFEMF
     YETWEKFDPD ATQFIAYSRL SDFVDTLQEP LRIAKPNKIK LITLDLPMVP GDKIHCLDIL
     FALTKEVLGD SGEMDALKQT MEEKFMAANP SKVSYEPITT TLKRKHEEVC AIKIQRAYRR
     HLLQRSMKQA SYMYRHSHDG SGDDAPEKEG LLANTMSKMY GHENGNSSSP SPEEKGEAGD
     AGPTMGLMPI SPSDTAWPPA PPPGQTVRPG VKESLV
//
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