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 27-MAR-2024, entry version 224. DE RecName: Full=Sodium channel protein type 4 subunit alpha; DE AltName: Full=SkM1 {ECO:0000303|PubMed:1315496}; 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS GLY-524; ASP-559 AND RP 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-dependent RT 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., Hoffmann E.P.; RT "Sequence and genomic structure of the human adult skeletal muscle sodium RT channel alpha subunit gene on 17q."; RL Biochem. Biophys. Res. Commun. 182:794-801(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, VARIANT CMS16 RP GLU-1442, VARIANTS LEU-246; GLY-524 AND ASP-559, CHARACTERIZATION OF RP VARIANT CMS16 GLU-1442, AND CHARACTERIZATION OF VARIANT LEU-246. 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., Gusella J.F.; RT "The genomic structure of the human skeletal muscle sodium channel 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., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., 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 the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1305-1339, AND VARIANTS PMC VAL-1306 RP 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 of RT the skeletal muscle sodium channel gene in paramyotonia 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., Wickenden A.D., RA 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 FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND INTERACTION WITH RP SCN1B. RX PubMed=29992740; DOI=10.1002/humu.23589; RA Baroni D., Picco C., Moran O.; RT "A mutation of SCN1B associated with GEFS+ causes functional and maturation RT defects of the voltage-dependent sodium channel."; RL Hum. Mutat. 39:1402-1415(2018). RN [9] RP SUBUNIT. RX PubMed=37117223; DOI=10.1038/s41467-023-37963-2; RA Jami S., Deuis J.R., Klasfauseweh T., Cheng X., Kurdyukov S., Chung F., RA Okorokov A.L., Li S., Zhang J., Cristofori-Armstrong B., Israel M.R., RA Ju R.J., Robinson S.D., Zhao P., Ragnarsson L., Andersson A., Tran P., RA Schendel V., McMahon K.L., Tran H.N.T., Chin Y.K., Zhu Y., Liu J., RA Crawford T., Purushothamvasan S., Habib A.M., Andersson D.A., Rash L.D., RA Wood J.N., Zhao J., Stehbens S.J., Mobli M., Leffler A., Jiang D., RA Cox J.J., Waxman S.G., Dib-Hajj S.D., Gregory Neely G., Durek T., RA Vetter I.; RT "Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 RT function."; RL Nat. Commun. 14:2442-2442(2023). RN [10] {ECO:0007744|PDB:6AGF} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH SCN1B, RP FUNCTION, ACTIVITY REGULATION, TOPOLOGY, SUBCELLULAR LOCATION, SUBUNIT, RP DOMAIN, GLYCOSYLATION AT ASN-362 AND ASN-1205, AND DISULFIDE BONDS. RX PubMed=30190309; DOI=10.1126/science.aau2486; RA Pan X., Li Z., Zhou Q., Shen H., Wu K., Huang X., Chen J., Zhang J., RA Zhu X., Lei J., Xiong W., Gong H., Xiao B., Yan N.; RT "Structure of the human voltage-gated sodium channel Nav1.4 in complex with RT beta1."; RL Science 362:0-0(2018). RN [11] 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 periodic RT paralysis."; RL Cell 67:1021-1027(1991). RN [12] 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-subunit in RT hyperkalaemic periodic paralysis."; RL Nature 354:387-389(1991). RN [13] 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 the RT skeletal muscle sodium channel."; RL Nat. Genet. 2:148-152(1992). RN [14] 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 channel RT cause paramyotonia congenita."; RL Neuron 8:891-897(1992). RN [15] 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., Barohn R.J., RA 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 [16] 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., Browatzki M., RA Weiss T., Rivet-Bastide M., Franke C., Lomonaco M., Ricker K., RA 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 [17] 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 [18] 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 congenita, RT paramyotonia congenita, and hyperkalemic periodic paralysis."; RL Neurology 44:1500-1503(1994). RN [19] 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., Hoffman E.P., RA Ebeid M.R.; RT "Hyperkalemic periodic paralysis with cardiac dysrhythmia: a novel sodium RT channel mutation?"; RL Ann. Neurol. 37:408-411(1995). RN [20] RP VARIANT PMC ILE-1293. RX PubMed=8580427; DOI=10.1097/00001756-199510010-00012; 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 [21] 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 [22] 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 [23] 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 channel RT alpha-subunit (SCN4A) that causes paramyotonia congenita of von RT Eulenburg."; RL Arch. Neurol. 56:692-696(1999). RN [24] 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 mutation RT associated with painful congenital myotonia."; RL FEBS Lett. 448:231-234(1999). RN [25] 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 [26] 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 new RT family with paramyotonia congenita."; RL J. Neurol. Neurosurg. Psych. 68:504-507(2000). RN [27] 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 and RT cold-induced paralysis."; RL Neurology 54:2179-2181(2000). RN [28] 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., Herzog J., RA Lerche H., Nicole S., Vale-Santos J., Chauveau D., Fontaine B., RA 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 [29] 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 acetazolamide- RT exacerbated hypokalemic periodic paralysis."; RL Ann. Neurol. 50:417-420(2001). RN [30] 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 [31] 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 R1448C and RT T1313M."; RL Muscle Nerve 30:277-288(2004). RN [32] 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., Kuntzer T., RA Eymard B., Hainque B., Fontaine B.; RT "New mutations of SCN4A cause a potassium-sensitive normokalemic periodic RT paralysis."; RL Neurology 63:2120-2127(2004). RN [33] 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., 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 [34] RP VARIANT PMC LYS-270, AND VARIANTS MYOSCN4A THR-715; ASN-804 AND 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 mutations RT causing myotonia."; RL Ann. Neurol. 60:356-365(2006). RN [35] 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., Fontaine B., RA Tabti N.; RT "Gating defects of a novel Na+ channel mutant causing hypokalemic periodic RT paralysis."; RL Biochem. Biophys. Res. Commun. 348:653-661(2006). RN [36] 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 [37] 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 [38] 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 heterozygous RT A1481D mutation in the SCN4A gene."; RL Muscle Nerve 35:599-606(2007). RN [39] 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 in RT French-Canadians."; RL Neurology 69:1937-1941(2007). RN [40] 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., Colombani M., RA Soichot P., Huet F., Hainque B., Sternberg D., Fontaine B., Gouyon J.B., RA Thauvin-Robinet C.; RT "Severe neonatal non-dystrophic myotonia secondary to a novel mutation of RT the voltage-gated sodium channel (SCN4A) gene."; RL Am. J. Med. Genet. A 146:380-383(2008). RN [41] 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 with RT normokalemic periodic paralysis."; RL Cell. Mol. Neurobiol. 28:653-661(2008). RN [42] RP CHARACTERIZATION OF VARIANTS PMC SER-1473 AND ILE-1705, FUNCTION, AND RP SUBCELLULAR LOCATION. 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 F1705I RT on sodium channel gating."; RL Channels 2:39-50(2008). RN [43] 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 [44] RP VARIANT HOKPP2 SER-1158, CHARACTERIZATION OF VARIANT HOKPP2 SER-1158, RP FUNCTION, AND SUBCELLULAR LOCATION. 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 [45] RP VARIANT MYOSCN4A VAL-141, AND CHARACTERIZATION OF VARIANT MYOSCN4A 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., Schorderet D., RA Abriel H., Burgunder J.M.; RT "A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to RT sodium channel myotonia."; RL Neurology 71:1669-1675(2008). RN [46] RP VARIANTS MYOSCN4A TRP-225; THR-1156 AND GLU-1306, VARIANT PMC THR-693, AND RP 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 sodium RT channelopathy."; RL J. Clin. Neurol. 5:186-191(2009). RN [47] RP VARIANT MYOSCN4A GLU-1633, CHARACTERIZATION OF VARIANT MYOSCN4A GLU-1633, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19347921; DOI=10.1002/mus.21155; RA Kubota T., Kinoshita M., Sasaki R., Aoike F., Takahashi M.P., Sakoda S., RA Hirose K.; RT "New mutation of the Na channel in the severe form of potassium-aggravated RT myotonia."; RL Muscle Nerve 39:666-673(2009). RN [48] 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 myotonia RT in French-Canadians."; RL Neuromuscul. Disord. 19:330-334(2009). RN [49] RP VARIANTS HOKPP2 TRP-222; CYS-672; GLY-672; HIS-672; SER-672; GLN-1132 AND RP 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., Chinnery P.F., RA Meola G., Schorge S., Kullmann D.M., Davis M.B., Hanna M.G.; RT "Voltage sensor charge loss accounts for most cases of hypokalemic periodic RT paralysis."; RL Neurology 72:1544-1547(2009). RN [50] 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 [51] 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 [52] 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 [53] RP VARIANTS HOKPP2 CYS-1135 AND HIS-1135, AND CHARACTERIZATION OF VARIANTS RP 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 IIIS4 RT movement during recovery."; RL Brain 137:998-1008(2014). RN [54] RP VARIANT CMS16 HIS-1457, CHARACTERIZATION OF VARIANT CMS16 HIS-1457, RP FUNCTION, AND SUBCELLULAR LOCATION. 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., Maselli R.A.; RT "Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic RT syndrome."; RL Ann. Neurol. 77:840-850(2015). RN [55] RP VARIANT SER-1537, AND CHARACTERIZATION OF VARIANT SER-1537. RX PubMed=26427606; DOI=10.1093/hmg/ddv410; RA Bergareche A., Bednarz M., Sanchez E., Krebs C.E., Ruiz-Martinez J., RA De La Riva P., Makarov V., Gorostidi A., Jurkat-Rott K., Marti-Masso J.F., RA Paisan-Ruiz C.; RT "SCN4A pore mutation pathogenetically contributes to autosomal dominant RT essential tremor and may increase susceptibility to epilepsy."; RL Hum. Mol. Genet. 24:7111-7120(2015). RN [56] RP VARIANT LEU-72, CHARACTERIZATION OF VARIANT LEU-72, AND INVOLVEMENT IN 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., Meola G.; RT "SCN4A mutation as modifying factor of myotonic dystrophy type 2 RT phenotype."; RL Neuromuscul. Disord. 25:301-307(2015). RN [57] RP VARIANTS CMYP22A HIS-104; TRP-225; ASN-1069; CYS-1135 AND PHE-1209, RP VARIANTS CMYP22B LYS-203; THR-382 AND 1593-TYR--VAL-1836 DEL, RP CHARACTERIZATION OF VARIANTS CMYP22A HIS-104; TRP-225; ASN-1069 AND RP PHE-1209, CHARACTERIZATION OF VARIANTS CMYP22B LYS-203 AND THR-382, RP INVOLVEMENT IN CMYP22A, INVOLVEMENT IN CMYP22B, FUNCTION, AND SUBCELLULAR RP LOCATION. 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., Sloerdahl A., RA Halvorsen H., Ye X.C., Zhang L.H., Loekken N., Werlauff U., Abdelsayed M., RA Davis M.R., Feng L., Phadke R., Sewry C.A., Morgan J.E., Laing N.G., RA Vallance H., Ruben P., Hanna M.G., Lewis S., Kamsteeg E.J., Maennikkoe R., RA Muntoni F.; RT "Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or RT 'classical' congenital myopathy."; RL Brain 139:674-691(2016). RN [58] 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., Uchida Y., RA Ikeda T., Mochizuki H., Nicole S., Fontaine B., Takahashi M.P., Mitake S.; RT "A case of non-dystrophic myotonia with concomitant mutations in the SCN4A RT and CLCN1 genes."; RL J. Neurol. Sci. 369:254-258(2016). RN [59] 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., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., 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., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). RN [60] RP VARIANT CMS16 TRP-1454, CHARACTERIZATION OF VARIANT CMS16 TRP-1454, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26659129; DOI=10.1212/wnl.0000000000002264; RA Habbout K., Poulin H., Rivier F., Giuliano S., Sternberg D., Fontaine B., RA Eymard B., Morales R.J., Echenne B., King L., Hanna M.G., Maennikkoe R., RA Chahine M., Nicole S., Bendahhou S.; RT "A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with RT periodic paralysis."; RL Neurology 86:161-169(2016). RN [61] RP VARIANTS CMYP22A ARG-375 AND GLN-1142, AND CHARACTERIZATION OF VARIANTS RP CMYP22A ARG-375 AND GLN-1142. RX PubMed=28262468; DOI=10.1016/j.nmd.2017.02.001; RA Gonorazky H.D., Marshall C.R., Al-Murshed M., Hazrati L.N., Thor M.G., RA Hanna M.G., Maennikkoe R., Ray P.N., Yoon G.; RT "Congenital myopathy with 'corona' fibres, selective muscle atrophy, and RT craniosynostosis associated with novel recessive mutations in SCN4A."; RL Neuromuscul. Disord. 27:574-580(2017). RN [62] RP VARIANTS CMYP22A LYS-1205 AND TRP-1454. RX PubMed=36090556; DOI=10.3389/fped.2022.944784; RA Berghold V.M., Koko M., Berutti R., Plecko B.; RT "Case report: Novel SCN4A variant associated with a severe congenital RT myasthenic syndrome/myopathy phenotype."; RL Front. Pediatr. 10:944784-944784(2022). CC -!- FUNCTION: Pore-forming subunit of a voltage-gated sodium channel CC complex through which Na(+) ions pass in accordance with their CC electrochemical gradient. Alternates between resting, activated and CC inactivated states (PubMed:12766226, PubMed:29992740, PubMed:30190309, CC PubMed:15318338, PubMed:16890191, PubMed:18690054, PubMed:17898326, CC PubMed:19347921, PubMed:25707578, PubMed:26700687). Required for normal CC muscle fiber excitability, normal muscle contraction and relaxation CC cycles, and constant muscle strength in the presence of fluctuating CC K(+) levels (PubMed:12766226, PubMed:15318338, PubMed:16890191, CC PubMed:19347921, PubMed:25707578, PubMed:26700687, PubMed:26659129). CC {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:15318338, CC ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326, CC ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19347921, CC ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129, CC ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:29992740, CC ECO:0000269|PubMed:30190309}. CC -!- ACTIVITY REGULATION: Channel activity is regulated by the ancillary CC beta subunit SCN1B (PubMed:29992740). SCN1B strongly enhances the CC presence of the pore-forming alpha subunit at the cell surface CC (PubMed:29992740, PubMed:30190309). Interaction with SCN1B is required CC for rapid channel inactivation and rapid recovery after inactivation, CC and prevents decrease of channel activity in response to repetitive, CC high-frequency depolarizations (By similarity). The channel is CC inhibited by tetrodotoxin and saxitoxin (PubMed:30190309). CC {ECO:0000250|UniProtKB:P15390, ECO:0000269|PubMed:29992740, CC ECO:0000269|PubMed:30190309}. CC -!- SUBUNIT: Component of a voltage-sensitive sodium channel complex that CC consists of an ion-conducting pore-forming alpha subunit and one or CC more regulatory beta subunits (PubMed:29992740, PubMed:30190309). CC Interacts with SCN1B (PubMed:29992740, PubMed:30190309). Heterooligomer CC with SCN2B or SCN4B; disulfide-linked (By similarity). Interacts with CC the PDZ domain of the syntrophins SNTA1, SNTB1 and SNTB2 (By CC similarity). Interacts with TMEM233 (PubMed:37117223). Interacts with CC the conotoxin GVIIJ (PubMed:24497506). {ECO:0000250|UniProtKB:P04775, CC ECO:0000250|UniProtKB:Q9ER60, ECO:0000269|PubMed:24497506, CC ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309, CC ECO:0000305|PubMed:37117223}. CC -!- INTERACTION: CC P35499; Q07699-1: SCN1B; NbExp=2; IntAct=EBI-16813249, EBI-20974499; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12766226, CC ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:16890191, CC ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18690054, CC ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:25707578, CC ECO:0000269|PubMed:26659129, ECO:0000269|PubMed:26700687, CC ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309}; Multi-pass CC membrane protein {ECO:0000269|PubMed:30190309}. CC -!- DOMAIN: The sequence contains 4 internal repeats, each with 5 CC hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged CC segment (S4). Segments S4 are probably the voltage-sensors and are CC characterized by a series of positively charged amino acids at every CC third position. {ECO:0000305|PubMed:30190309}. CC -!- PTM: Phosphorylation at Ser-1328 by PKC in a highly conserved CC cytoplasmic loop slows inactivation of the sodium channel and reduces CC peak sodium currents. {ECO:0000250}. CC -!- DISEASE: Paramyotonia congenita (PMC) [MIM:168300]: An autosomal CC dominant channelopathy characterized by myotonia, increased by exposure CC to cold, intermittent flaccid paresis, not necessarily dependent on CC cold or myotonia, lability of serum potassium, non-progressive nature CC and lack of atrophy or hypertrophy of muscles. In some patients, CC myotonia is not increased by cold exposure (paramyotonia without cold CC paralysis). 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 variants affecting the gene represented in this CC entry. CC -!- DISEASE: Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An CC autosomal dominant disorder manifested by episodic flaccid generalized CC muscle weakness associated with falls of serum potassium levels. CC {ECO:0000269|PubMed:10599760, ECO:0000269|PubMed:10851391, CC ECO:0000269|PubMed:10944223, ECO:0000269|PubMed:11558801, CC ECO:0000269|PubMed:11591859, ECO:0000269|PubMed:16890191, CC ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18162704, CC ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:20522878, CC ECO:0000269|PubMed:21043388, ECO:0000269|PubMed:24549961}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 variants CC 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 marked CC by a lack of alterations in potassium levels during attacks of muscle CC weakness. {ECO:0000269|PubMed:15596759, ECO:0000269|PubMed:18046642, CC ECO:0000269|PubMed:20522878}. Note=The disease is caused by variants CC affecting the gene 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 sustained CC muscle tensing that prevents muscles from relaxing normally. It causes CC muscle stiffness that can interfere with movement. In some people the CC stiffness is very mild, while in other cases it may be severe enough to CC interfere with walking, running, and other activities of daily life. CC Myotonia SCN4A-related includes myotonia permanens and myotonia CC fluctuans. In myotonia permanens, the myotonia is generalized and there CC is a hypertrophy of the muscle, particularly in the neck and the CC shoulder. Attacks of severe muscle stiffness of the thoracic muscles CC may be life threatening due to impaired ventilation. In myotonia CC fluctuans, the muscle stiffness may fluctuate from day to day, provoked CC by exercise. {ECO:0000269|PubMed:10218481, ECO:0000269|PubMed:16786525, CC ECO:0000269|PubMed:16832098, ECO:0000269|PubMed:17212350, CC ECO:0000269|PubMed:17998485, ECO:0000269|PubMed:18203179, CC ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:19015483, CC ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:20076800, CC ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:8058156, CC ECO:0000269|PubMed:9392583}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myasthenic syndrome, congenital, 16 (CMS16) [MIM:614198]: A CC form of congenital myasthenic syndrome, a group of disorders CC characterized by failure of neuromuscular transmission, including pre- CC synaptic, synaptic, and post-synaptic disorders that are not of CC autoimmune origin. Clinical features are easy fatigability and muscle CC weakness. CMS16 is characterized by fatigable generalized weakness and CC recurrent attacks of respiratory and bulbar paralysis since birth. The CC fatigable weakness involves lid-elevator, external ocular, facial, limb CC and truncal muscles and an decremental response of the compound muscle CC action potential on repetitive stimulation. CC {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:25707578, CC ECO:0000269|PubMed:26659129}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Congenital myopathy 22A, classic (CMYP22A) [MIM:620351]: A CC form of congenital myopathy, a clinically and genetically heterogeneous CC group of muscle disorders characterized by hypotonia and muscle CC weakness apparent at birth, and specific pathological features on CC muscle biopsy. CMYP22A is an autosomal recessive form characterized by CC fetal hypokinesia, polyhydramnios, and severe neonatal hypotonia CC associated with respiratory insufficiency. Affected individuals who CC survive the neonatal period have delayed motor development, difficulty CC walking, proximal muscle weakness of the upper and lower limbs, facial CC and neck muscle weakness, easy fatigability, and mild limb contractures CC or foot deformities. {ECO:0000269|PubMed:26700687, CC ECO:0000269|PubMed:28262468, ECO:0000269|PubMed:36090556}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Congenital myopathy 22B, severe fetal (CMYP22B) [MIM:620369]: CC A severe congenital myopathy, a clinically and genetically CC heterogeneous group of muscle disorders characterized by hypotonia and CC muscle weakness apparent at birth, and specific pathological features CC on muscle biopsy. CMYP22B is an autosomal recessive form characterized CC by onset in utero. Affected individuals show fetal akinesia, and CC develop fetal hydrops with pulmonary hypoplasia, severe joint CC contractures, and generalized muscle hypoplasia. Death occurs in utero CC or soon after birth. {ECO:0000269|PubMed:26700687}. Note=The disease is CC caused by variants affecting the gene represented in this entry. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 6AGF; EM; 3.20 A; A=1-1836. DR PDB; 6MBA; X-ray; 1.80 A; A=1599-1764. DR PDB; 6MC9; X-ray; 3.30 A; A=1599-1754. DR PDBsum; 6AGF; -. DR PDBsum; 6MBA; -. DR PDBsum; 6MC9; -. DR AlphaFoldDB; P35499; -. DR EMDB; EMD-9617; -. DR SMR; P35499; -. DR BioGRID; 112234; 89. DR IntAct; P35499; 7. DR STRING; 9606.ENSP00000396320; -. DR BindingDB; P35499; -. DR ChEMBL; CHEMBL2072; -. DR DrugBank; DB09088; Amylocaine. DR DrugBank; DB13746; Bioallethrin. DR DrugBank; DB05541; Brivaracetam. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB01161; Chloroprocaine. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB13269; Dichlorobenzyl alcohol. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB13961; Fish oil. DR DrugBank; DB01195; Flecainide. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00776; Oxcarbazepine. DR DrugBank; DB13154; Parachlorophenol. DR DrugBank; DB11186; Pentoxyverine. DR DrugBank; DB09345; Pramocaine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB00818; Propofol. DR DrugBank; DB09342; Propoxycaine. DR DrugBank; DB00243; Ranolazine. DR DrugBank; DB09085; Tetracaine. DR DrugBank; DB00273; Topiramate. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB00909; Zonisamide. DR DrugCentral; P35499; -. DR GuidetoPHARMACOLOGY; 581; -. DR TCDB; 1.A.1.10.4; the voltage-gated ion channel (vic) superfamily. DR GlyConnect; 1752; 2 N-Linked glycans (2 sites). DR GlyCosmos; P35499; 12 sites, 3 glycans. DR GlyGen; P35499; 13 sites, 3 N-linked glycans (2 sites). DR iPTMnet; P35499; -. DR PhosphoSitePlus; P35499; -. DR BioMuta; SCN4A; -. DR DMDM; 292495096; -. DR EPD; P35499; -. DR MassIVE; P35499; -. DR PaxDb; 9606-ENSP00000396320; -. DR PeptideAtlas; P35499; -. DR ProteomicsDB; 55071; -. DR ABCD; P35499; 3 sequenced antibodies. DR Antibodypedia; 57204; 105 antibodies from 21 providers. DR DNASU; 6329; -. DR Ensembl; ENST00000435607.3; ENSP00000396320.1; ENSG00000007314.12. DR GeneID; 6329; -. DR KEGG; hsa:6329; -. DR MANE-Select; ENST00000435607.3; ENSP00000396320.1; NM_000334.4; NP_000325.4. DR UCSC; uc002jds.1; human. DR AGR; HGNC:10591; -. DR CTD; 6329; -. DR DisGeNET; 6329; -. DR GeneCards; SCN4A; -. DR GeneReviews; SCN4A; -. DR HGNC; HGNC:10591; SCN4A. DR HPA; ENSG00000007314; Group enriched (skeletal muscle, tongue). 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 MIM; 620351; phenotype. DR MIM; 620369; 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 VEuPathDB; HostDB:ENSG00000007314; -. DR eggNOG; KOG2301; Eukaryota. DR GeneTree; ENSGT00940000159417; -. DR HOGENOM; CLU_000540_5_0_1; -. DR InParanoid; P35499; -. DR OMA; MSKMYGP; -. DR OrthoDB; 1110761at2759; -. DR PhylomeDB; P35499; -. DR TreeFam; TF323985; -. DR PathwayCommons; P35499; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation. DR SignaLink; P35499; -. DR SIGNOR; P35499; -. DR BioGRID-ORCS; 6329; 16 hits in 1152 CRISPR screens. DR ChiTaRS; SCN4A; human. DR GeneWiki; Nav1.4; -. DR GenomeRNAi; 6329; -. DR Pharos; P35499; Tclin. DR PRO; PR:P35499; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P35499; Protein. DR Bgee; ENSG00000007314; Expressed in hindlimb stylopod muscle and 108 other cell types or tissues. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central. DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:UniProtKB. DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IBA:GO_Central. DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB. DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR GO; GO:0100001; P:regulation of skeletal muscle contraction by action potential; IMP:UniProtKB. DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0006814; P:sodium ion transport; TAS:ProtInc. DR CDD; cd13433; Na_channel_gate; 1. DR Gene3D; 1.10.287.70; -; 4. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 1.20.5.1190; iswi atpase; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 4. 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; IPR044564; Na_chnl_inactivation_gate. DR InterPro; IPR010526; Na_trans_assoc_dom. DR InterPro; IPR043203; VGCC_Ca_Na. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR10037:SF223; SODIUM CHANNEL PROTEIN TYPE 4 SUBUNIT ALPHA; 1. DR PANTHER; PTHR10037; VOLTAGE-GATED CATION CHANNEL CALCIUM AND SODIUM; 1. DR Pfam; PF00520; Ion_trans; 4. DR Pfam; PF06512; Na_trans_assoc; 1. DR PRINTS; PR00170; NACHANNEL. DR PRINTS; PR01665; NACHANNEL4. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR PROSITE; PS50096; IQ; 1. DR Genevisible; P35499; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Congenital myasthenic syndrome; KW Disease variant; Disulfide bond; Glycoprotein; Ion channel; Ion transport; KW Membrane; Phosphoprotein; Reference proteome; Repeat; Sodium; KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix; KW Transport; Voltage-gated channel. FT CHAIN 1..1836 FT /note="Sodium channel protein type 4 subunit alpha" FT /id="PRO_0000048495" FT TOPO_DOM 1..131 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 132..150 FT /note="Helical; Name=S1 of repeat I" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 151..157 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 158..178 FT /note="Helical; Name=S2 of repeat I" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 179..192 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 193..210 FT /note="Helical; Name=S3 of repeat I" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 211..216 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 217..233 FT /note="Helical; Name=S4 of repeat I" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 234..252 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 253..272 FT /note="Helical; Name=S5 of repeat I" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 273..391 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT INTRAMEM 392..416 FT /note="Pore-forming" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 417..423 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 424..444 FT /note="Helical; Name=S6 of repeat I" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 445..578 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 579..597 FT /note="Helical; Name=S1 of repeat II" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 598..608 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 609..628 FT /note="Helical; Name=S2 of repeat II" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 629..642 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 643..662 FT /note="Helical; Name=S3 of repeat II" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 663..664 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 665..682 FT /note="Helical; Name=S4 of repeat II" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 683..698 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 699..717 FT /note="Helical; Name=S5 of repeat II" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 718..746 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT INTRAMEM 747..767 FT /note="Pore-forming" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 768..778 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 779..797 FT /note="Helical; Name=S6 of repeat II" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 798..1032 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1033..1050 FT /note="Helical; Name=S1 of repeat III" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1051..1063 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1064..1082 FT /note="Helical; Name=S2 of repeat III" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1083..1096 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1097..1115 FT /note="Helical; Name=S3 of repeat III" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1116..1123 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1124..1142 FT /note="Helical; Name=S4 of repeat III" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1143..1159 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1160..1179 FT /note="Helical; Name=S5 of repeat III" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1180..1230 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT INTRAMEM 1231..1252 FT /note="Pore-forming" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1253..1269 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1270..1291 FT /note="Helical; Name=S6 of repeat III" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1292..1354 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1355..1372 FT /note="Helical; Name=S1 of repeat IV" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1373..1383 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1384..1402 FT /note="Helical; Name=S2 of repeat IV" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1403..1414 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1415..1432 FT /note="Helical; Name=S3 of repeat IV" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1433..1445 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1446..1462 FT /note="Helical; Name=S4 of repeat IV" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1463..1481 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1482..1499 FT /note="Helical; Name=S5 of repeat IV" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1500..1521 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT INTRAMEM 1522..1544 FT /note="Pore-forming" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1545..1574 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30190309" FT TRANSMEM 1575..1597 FT /note="Helical; Name=S6 of repeat IV" FT /evidence="ECO:0000269|PubMed:30190309" FT TOPO_DOM 1598..1836 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30190309" FT REPEAT 113..454 FT /note="I" FT /evidence="ECO:0000305" FT REPEAT 560..832 FT /note="II" FT /evidence="ECO:0000305" FT REPEAT 1013..1326 FT /note="III" FT /evidence="ECO:0000305" FT REPEAT 1335..1633 FT /note="IV" FT /evidence="ECO:0000305" FT DOMAIN 1727..1756 FT /note="IQ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT REGION 39..63 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 493..530 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 863..886 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 930..992 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1310..1312 FT /note="Important for rapid channel inactivation" FT /evidence="ECO:0000250|UniProtKB:P15390" FT REGION 1778..1836 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 39..59 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 507..530 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 872..886 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 975..990 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1779..1793 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 407 FT /note="Important for inhibition by tetrodotoxin" FT /evidence="ECO:0000250|UniProtKB:P15390" FT MOD_RES 1328 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000250" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 288 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 291 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 297 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 303 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 315 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 321 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 333 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 362 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT CARBOHYD 1191 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1205 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT DISULFID 280..360 FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT DISULFID 369..375 FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT DISULFID 729 FT /note="Interchain; with SCN2B or SCN4B" FT /evidence="ECO:0000250|UniProtKB:P04775" FT DISULFID 729 FT /note="Interchain; with the conotoxin GVIIJ (when the FT channel is not linked to SCN2B or SCN4B; the bond to SCN2B FT or SCN4B protects the channel from the inhibition by FT toxin)" FT /evidence="ECO:0000250|UniProtKB:P04775" FT DISULFID 731..737 FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT DISULFID 769..778 FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT DISULFID 1189..1209 FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT DISULFID 1553..1568 FT /evidence="ECO:0000269|PubMed:30190309, FT ECO:0007744|PDB:6AGF" FT VARIANT 72 FT /note="P -> L (found in a patient with severe dystrophia FT myotonica 2; uncertain significance; the patient carries a FT disease-causing CCTG repeat expansion in CNBP; may act as a FT disease modifier; changes the voltage-gated sodium channel FT activity; increases membrane hyperexcitability; decreases FT channel fast inactivation; dbSNP:rs1303471186)" FT /evidence="ECO:0000269|PubMed:25660391" FT /id="VAR_074598" FT VARIANT 104 FT /note="R -> H (in CMYP22A; likely pathogenic; loss of FT sodium ion transmembrane transport; dbSNP:rs1248025530)" FT /evidence="ECO:0000269|PubMed:26700687" FT /id="VAR_075430" FT VARIANT 135 FT /note="M -> V" FT /id="VAR_001560" FT VARIANT 141 FT /note="I -> V (in MYOSCN4A; causes a hyperpolarizing shift FT of the activation curve; enhances channel slow FT inactivation; dbSNP:rs121908561)" FT /evidence="ECO:0000269|PubMed:19015483" FT /id="VAR_054934" FT VARIANT 203 FT /note="M -> K (in CMYP22B; likely pathogenic; impaired FT sodium ion transmembrane transport; dbSNP:rs933258893)" FT /evidence="ECO:0000269|PubMed:26700687" FT /id="VAR_075431" FT VARIANT 222 FT /note="R -> W (in HOKPP2; dbSNP:rs527236148)" FT /evidence="ECO:0000269|PubMed:19118277" FT /id="VAR_054935" FT VARIANT 225 FT /note="R -> W (in MYOSCN4A and CMYP22A; impaired sodium ion FT transmembrane transport; dbSNP:rs764718003)" FT /evidence="ECO:0000269|PubMed:20076800, FT ECO:0000269|PubMed:26700687" FT /id="VAR_065230" FT VARIANT 246 FT /note="S -> L (no significant effect on channel activity; FT dbSNP:rs80338951)" FT /evidence="ECO:0000269|PubMed:12766226" FT /id="VAR_017785" FT VARIANT 270 FT /note="Q -> K (in PMC; dbSNP:rs1597985462)" FT /evidence="ECO:0000269|PubMed:16786525, FT ECO:0000269|PubMed:18166706" FT /id="VAR_054936" FT VARIANT 375 FT /note="C -> R (in CMYP22A; likely pathogenic; loss of FT sodium ion transmembrane transport)" FT /evidence="ECO:0000269|PubMed:28262468" FT /id="VAR_088556" FT VARIANT 382 FT /note="P -> T (in CMYP22B; likely pathogenic; loss of FT sodium ion transmembrane transport)" FT /evidence="ECO:0000269|PubMed:26700687" FT /id="VAR_075432" FT VARIANT 445 FT /note="V -> M (in MYOSCN4A; dbSNP:rs121908552)" FT /evidence="ECO:0000269|PubMed:10218481, FT ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:9392583" FT /id="VAR_017786" FT VARIANT 452 FT /note="E -> K (in MYOSCN4A; variable phenotype ranging from FT mild to severe myotonia; dbSNP:rs372631097)" FT /evidence="ECO:0000269|PubMed:18337100" FT /id="VAR_054937" FT VARIANT 524 FT /note="S -> G (in dbSNP:rs6504191)" FT /evidence="ECO:0000269|PubMed:12766226, FT ECO:0000269|PubMed:1315496, ECO:0000269|PubMed:1339144" FT /id="VAR_001561" FT VARIANT 559 FT /note="N -> D (in dbSNP:rs1047705)" FT /evidence="ECO:0000269|PubMed:12766226, FT ECO:0000269|PubMed:1315496" FT /id="VAR_017787" FT VARIANT 669 FT /note="R -> H (in HOKPP2; dbSNP:rs80338784)" FT /evidence="ECO:0000269|PubMed:10599760, FT ECO:0000269|PubMed:18162704" FT /id="VAR_017788" FT VARIANT 671 FT /note="F -> S (in MYOSCN4A)" FT /evidence="ECO:0000269|PubMed:18337100" FT /id="VAR_054938" FT VARIANT 672 FT /note="R -> C (in HOKPP2; dbSNP:rs80338785)" FT /evidence="ECO:0000269|PubMed:18162704, FT ECO:0000269|PubMed:19118277" FT /id="VAR_054939" FT VARIANT 672 FT /note="R -> G (in HOKPP2; dbSNP:rs80338785)" FT /evidence="ECO:0000269|PubMed:10944223, FT ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277" FT /id="VAR_017789" FT VARIANT 672 FT /note="R -> H (in HOKPP2; dbSNP:rs80338788)" FT /evidence="ECO:0000269|PubMed:10944223, FT ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:21043388" FT /id="VAR_017790" FT VARIANT 672 FT /note="R -> S (in HOKPP2; dbSNP:rs80338785)" FT /evidence="ECO:0000269|PubMed:11558801, FT ECO:0000269|PubMed:11591859, ECO:0000269|PubMed:19118277" FT /id="VAR_017791" FT VARIANT 675 FT /note="R -> G (in NKPP; dbSNP:rs121908556)" FT /evidence="ECO:0000269|PubMed:15596759" FT /id="VAR_037104" FT VARIANT 675 FT /note="R -> Q (in NKPP; dbSNP:rs121908557)" FT /evidence="ECO:0000269|PubMed:15596759, FT ECO:0000269|PubMed:18046642" FT /id="VAR_037105" FT VARIANT 675 FT /note="R -> W (in NKPP; dbSNP:rs121908556)" FT /evidence="ECO:0000269|PubMed:15596759" FT /id="VAR_037106" FT VARIANT 693 FT /note="I -> T (in PMC; dbSNP:rs80338956)" FT /evidence="ECO:0000269|PubMed:20076800" FT /id="VAR_065231" FT VARIANT 704 FT /note="T -> M (in HYPP and PMC; dbSNP:rs80338957)" FT /evidence="ECO:0000269|PubMed:1659948, FT ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:19077043" FT /id="VAR_001562" FT VARIANT 715 FT /note="A -> T (in MYOSCN4A; dbSNP:rs749400108)" FT /evidence="ECO:0000269|PubMed:16786525" FT /id="VAR_054940" FT VARIANT 781 FT /note="V -> I (voltage-gated sodium channel activity is not FT affected and channel activation as well as fast and slow FT inactivation curves are normal; dbSNP:rs62070884)" FT /evidence="ECO:0000269|PubMed:18046642, FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:7695243, FT ECO:0000269|PubMed:9266738" FT /id="VAR_054941" FT VARIANT 804 FT /note="S -> F (in PMC; dbSNP:rs121908546)" FT /evidence="ECO:0000269|PubMed:1338909" FT /id="VAR_001563" FT VARIANT 804 FT /note="S -> N (in MYOSCN4A)" FT /evidence="ECO:0000269|PubMed:16786525" FT /id="VAR_054942" FT VARIANT 861 FT /note="A -> D" FT /id="VAR_001564" FT VARIANT 1069 FT /note="D -> N (in CMYP22A; likely pathogenic; impaired FT sodium ion transmembrane transport; dbSNP:rs373150395)" FT /evidence="ECO:0000269|PubMed:26700687" FT /id="VAR_075433" FT VARIANT 1129 FT /note="R -> Q (in NKPP and HOKPP2; dbSNP:rs527236149)" FT /evidence="ECO:0000269|PubMed:20522878" FT /id="VAR_064987" FT VARIANT 1132 FT /note="R -> Q (in HOKPP2; changes the voltage-gated sodium FT channel activity; increases membrane hypoexcitability; FT increases channel activation and both fast and slow channel FT inactivation; dbSNP:rs80338789)" FT /evidence="ECO:0000269|PubMed:16890191, FT ECO:0000269|PubMed:19118277" FT /id="VAR_054943" FT VARIANT 1135 FT /note="R -> C (in HOKPP2 and CMYP22A; increased FT depolarization tendency at normal and reduced extracellular FT potassium and reduced amplitude and rise time of action FT potentials; dbSNP:rs1287863349)" FT /evidence="ECO:0000269|PubMed:24549961, FT ECO:0000269|PubMed:26700687" FT /id="VAR_075434" FT VARIANT 1135 FT /note="R -> H (in HOKPP2; increased depolarization tendency FT at normal and reduced extracellular potassium and reduced FT amplitude and rise time of action potentials; FT dbSNP:rs527236150)" FT /evidence="ECO:0000269|PubMed:19118277, FT ECO:0000269|PubMed:24549961" FT /id="VAR_054944" FT VARIANT 1142 FT /note="R -> Q (in CMYP22A; likely pathogenic; decreased FT sodium ion transmembrane transport)" FT /evidence="ECO:0000269|PubMed:28262468" FT /id="VAR_088557" FT VARIANT 1152 FT /note="A -> D (in PMC)" FT /evidence="ECO:0000269|PubMed:15790667" FT /id="VAR_022341" FT VARIANT 1156 FT /note="A -> T (in PMC, MYOSCN4A and HYPP; FT dbSNP:rs80338958)" FT /evidence="ECO:0000269|PubMed:1338909, FT ECO:0000269|PubMed:20076800" FT /id="VAR_001565" FT VARIANT 1158 FT /note="P -> S (in HOKPP2; atypical phenotype with FT heat-induced myotonia and cold-induced paralysis with FT hypokalemia; changes the voltage-gated sodium channel FT activity; increases channel activation and slow FT inactivation at low temperature; dbSNP:rs121908555)" FT /evidence="ECO:0000269|PubMed:10851391, FT ECO:0000269|PubMed:17898326" FT /id="VAR_017792" FT VARIANT 1160 FT /note="I -> V (in MYOSCN4A; acetazolamide-responsive FT myotonia; dbSNP:rs121908549)" FT /evidence="ECO:0000269|PubMed:8058156" FT /id="VAR_017793" FT VARIANT 1205 FT /note="N -> K (in CMYP22A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:36090556" FT /id="VAR_088558" FT VARIANT 1209 FT /note="C -> F (in CMYP22A; likely pathogenic; loss of FT sodium ion transmembrane transport)" FT /evidence="ECO:0000269|PubMed:26700687" FT /id="VAR_075435" FT VARIANT 1290 FT /note="F -> L (in MYOSCN4A; enhances voltage-gated sodium FT channel activation inducing membrane hyperexcitability)" FT /evidence="ECO:0000269|PubMed:27653901" FT /id="VAR_079519" FT VARIANT 1293 FT /note="V -> I (in PMC; without cold paralysis; FT dbSNP:rs121908551)" FT /evidence="ECO:0000269|PubMed:8580427" FT /id="VAR_001566" FT VARIANT 1297 FT /note="N -> K (in MYOSCN4A; unusually severe and lethal FT phenotype with neonatal onset; dbSNP:rs121908560)" FT /evidence="ECO:0000269|PubMed:18203179" FT /id="VAR_054945" FT VARIANT 1306 FT /note="G -> A (in PMC; dbSNP:rs80338792)" FT /evidence="ECO:0000269|PubMed:18166706, FT ECO:0000269|PubMed:8308722" FT /id="VAR_001567" FT VARIANT 1306 FT /note="G -> E (in MYOSCN4A and PMC; severe; FT dbSNP:rs80338792)" FT /evidence="ECO:0000269|PubMed:16832098, FT ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:20076800, FT ECO:0000269|PubMed:8308722" FT /id="VAR_001568" FT VARIANT 1306 FT /note="G -> V (in MYOSCN4A and PMC; dbSNP:rs80338792)" FT /evidence="ECO:0000269|PubMed:1310898, FT ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:8308722" FT /id="VAR_001569" FT VARIANT 1310 FT /note="I -> N (in MYOSCN4A; dbSNP:rs1567817380)" FT /evidence="ECO:0000269|PubMed:16786525" FT /id="VAR_054946" FT VARIANT 1313 FT /note="T -> M (in PMC; changes the voltage-gated sodium FT channel activity; increases membrane hyperexcitability at FT low temperature; decreases channel activation, FT deactivation, fast inactivation and recovery delay from FT fast inactivation; dbSNP:rs121908547)" FT /evidence="ECO:0000269|PubMed:1310898, FT ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:18166706" FT /id="VAR_001570" FT VARIANT 1376 FT /note="N -> D (in dbSNP:rs2058194)" FT /evidence="ECO:0000269|PubMed:1315496" FT /id="VAR_017794" FT VARIANT 1433 FT /note="L -> R (in PMC and HYPP; dbSNP:rs121908550)" FT /evidence="ECO:0000269|PubMed:8388676" FT /id="VAR_001571" FT VARIANT 1436 FT /note="L -> P (in PMC; dbSNP:rs1598405334)" FT /evidence="ECO:0000269|PubMed:18166706" FT /id="VAR_054947" FT VARIANT 1442 FT /note="V -> E (in CMS16; leads to fast inactivation; FT dbSNP:rs121908553)" FT /evidence="ECO:0000269|PubMed:12766226" FT /id="VAR_017795" FT VARIANT 1448 FT /note="R -> C (in PMC; changes the voltage-gated sodium FT channel activity; increases membrane hyperexcitability at FT low temperature; decreases channel activation, FT deactivation, fast inactivation and recovery delay from FT fast inactivation; dbSNP:rs121908544)" FT /evidence="ECO:0000269|PubMed:1316765, FT ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:18166706" FT /id="VAR_001572" FT VARIANT 1448 FT /note="R -> H (in PMC; dbSNP:rs121908545)" FT /evidence="ECO:0000269|PubMed:1316765, FT ECO:0000269|PubMed:18166706" FT /id="VAR_001573" FT VARIANT 1448 FT /note="R -> L (in PMC; dbSNP:rs121908545)" FT /evidence="ECO:0000269|PubMed:18166706" FT /id="VAR_054948" FT VARIANT 1454 FT /note="R -> W (in CMS16 and CMYP22A; leads to FT hyperpolarization of the steady-state fast inactivation, FT slow recovery from inactivation and reduces the channel FT ability to activate in response to repetitive stimulating FT pulses; dbSNP:rs879253789)" FT /evidence="ECO:0000269|PubMed:26659129, FT ECO:0000269|PubMed:36090556" FT /id="VAR_075436" FT VARIANT 1456 FT /note="G -> E (in PMC; dbSNP:rs121908554)" FT /evidence="ECO:0000269|PubMed:10369308, FT ECO:0000269|PubMed:10727489, ECO:0000269|PubMed:18166706" FT /id="VAR_037107" FT VARIANT 1457 FT /note="R -> H (in CMS16; enhanced fast inactivation and FT slowed recovery from fast inactivation; dbSNP:rs863225046)" FT /evidence="ECO:0000269|PubMed:25707578" FT /id="VAR_075437" FT VARIANT 1473 FT /note="F -> S (in PMC; accelerates deactivation from the FT inactivated state and enhances the remobilization of gating FT charge)" FT /evidence="ECO:0000269|PubMed:18166706, FT ECO:0000269|PubMed:18690054" FT /id="VAR_054949" FT VARIANT 1476 FT /note="M -> I (in MYOSCN4A; highly variable severity; FT dbSNP:rs121908559)" FT /evidence="ECO:0000269|PubMed:17998485, FT ECO:0000269|PubMed:18337100" FT /id="VAR_054950" FT VARIANT 1481 FT /note="A -> D (in MYOSCN4A; fluctuating cold-induced and FT exercise-induced stiffness; dbSNP:rs763893717)" FT /evidence="ECO:0000269|PubMed:17212350" FT /id="VAR_054951" FT VARIANT 1537 FT /note="G -> S (found in a patient with variable FT manifestations of essential tremor; uncertain significance; FT the channel has a tendency toward faster activation and FT significantly faster inactivation at near-threshold FT potentials; dbSNP:rs571210585)" FT /evidence="ECO:0000269|PubMed:26427606" FT /id="VAR_088559" FT VARIANT 1589 FT /note="V -> M (in PMC; dbSNP:rs121908548)" FT /evidence="ECO:0000269|PubMed:18166706, FT ECO:0000269|PubMed:8242056" FT /id="VAR_001574" FT VARIANT 1592 FT /note="M -> V (in HYPP and NKPP; dbSNP:rs80338962)" FT /evidence="ECO:0000269|PubMed:1659668, FT ECO:0000269|PubMed:18046642" FT /id="VAR_001575" FT VARIANT 1593..1836 FT /note="Missing (in CMYP22B; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:26700687" FT /id="VAR_088560" FT VARIANT 1633 FT /note="Q -> E (in MYOSCN4A; changes the voltage-gated FT sodium channel activity; increases membrane FT hyperexcitability; decreases channel fast inactivation)" FT /evidence="ECO:0000269|PubMed:19347921" FT /id="VAR_074581" FT VARIANT 1705 FT /note="F -> I (in PMC; increases the extent of charge FT immobilization in response to strong depolarization; FT dbSNP:rs1064794243)" FT /evidence="ECO:0000269|PubMed:18690054" FT /id="VAR_054952" FT CONFLICT 10..11 FT /note="VP -> AR (in Ref. 1; AAA60554)" FT /evidence="ECO:0000305" FT CONFLICT 371 FT /note="E -> K (in Ref. 1; AAA60554)" FT /evidence="ECO:0000305" FT CONFLICT 371 FT /note="E -> Q (in Ref. 1; AAB59624)" FT /evidence="ECO:0000305" FT CONFLICT 870 FT /note="A -> G (in Ref. 1; AAB59624)" FT /evidence="ECO:0000305" FT CONFLICT 1151..1152 FT /note="NA -> KP (in Ref. 1; AAB59624)" FT /evidence="ECO:0000305" FT HELIX 121..128 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 133..147 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 158..179 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 184..188 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 194..209 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 219..227 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 228..232 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 245..248 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 251..272 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 338..342 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 362..366 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 373..377 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 389..391 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 392..397 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 400..403 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 408..419 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 421..423 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 424..433 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 434..438 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 439..453 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 455..462 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 561..576 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 577..580 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 581..595 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 604..631 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 634..639 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 641..659 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 668..670 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 672..680 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 686..697 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 698..702 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 703..726 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 730..732 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 744..746 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 747..759 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 764..772 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 775..802 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1015..1028 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1031..1046 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1053..1055 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1060..1078 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1081..1087 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1090..1093 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1095..1097 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1098..1116 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1117..1119 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 1123..1129 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1130..1141 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1144..1153 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1154..1156 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1157..1182 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1188..1191 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 1192..1194 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 1200..1202 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1206..1209 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1210..1212 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1218..1221 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1230..1241 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1246..1255 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1269..1271 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1272..1281 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1284..1304 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1305..1309 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1316..1324 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 1325..1328 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1341..1343 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1347..1350 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1354..1362 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1365..1371 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1379..1404 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 1408..1413 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1415..1439 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1444..1446 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1447..1450 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1451..1463 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1468..1503 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1504..1506 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1515..1521 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1522..1531 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1532..1534 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1538..1542 FT /evidence="ECO:0007829|PDB:6AGF" FT TURN 1543..1545 FT /evidence="ECO:0007829|PDB:6AGF" FT STRAND 1549..1553 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1571..1605 FT /evidence="ECO:0007829|PDB:6AGF" FT HELIX 1614..1627 FT /evidence="ECO:0007829|PDB:6MBA" FT STRAND 1633..1636 FT /evidence="ECO:0007829|PDB:6MBA" FT HELIX 1637..1639 FT /evidence="ECO:0007829|PDB:6MBA" FT HELIX 1640..1646 FT /evidence="ECO:0007829|PDB:6MBA" FT TURN 1649..1651 FT /evidence="ECO:0007829|PDB:6MBA" FT HELIX 1658..1663 FT /evidence="ECO:0007829|PDB:6MBA" FT STRAND 1667..1669 FT /evidence="ECO:0007829|PDB:6MBA" FT TURN 1670..1672 FT /evidence="ECO:0007829|PDB:6MBA" FT STRAND 1673..1675 FT /evidence="ECO:0007829|PDB:6MBA" FT HELIX 1676..1688 FT /evidence="ECO:0007829|PDB:6MBA" FT HELIX 1692..1705 FT /evidence="ECO:0007829|PDB:6MBA" FT STRAND 1718..1720 FT /evidence="ECO:0007829|PDB:6MBA" FT HELIX 1721..1745 FT /evidence="ECO:0007829|PDB:6MBA" 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 //