ID SCN2A_HUMAN Reviewed; 2005 AA. AC Q99250; A6NC14; A6NIQ5; Q14472; Q53T77; Q9BZC9; Q9BZD0; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 08-NOV-2002, sequence version 3. DT 27-MAR-2024, entry version 227. DE RecName: Full=Sodium channel protein type 2 subunit alpha {ECO:0000305}; DE AltName: Full=HBSC II; DE AltName: Full=Sodium channel protein brain II subunit alpha; DE AltName: Full=Sodium channel protein type II subunit alpha; DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.2; GN Name=SCN2A {ECO:0000312|HGNC:HGNC:10588}; GN Synonyms=HBA {ECO:0000303|PubMed:1325650}, NAC2, SCN2A1, SCN2A2; 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 [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY, AND RP SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=1325650; DOI=10.1073/pnas.89.17.8220; RA Ahmed C.M., Ware D.H., Lee S.C., Patten C.D., Ferrer-Montiel A.V., RA Schinder A.F., McPherson J.D., Wagner-Mcpherson C.B., Wasmuth J.J., RA Evans G.A., Montal M.; RT "Primary structure, chromosomal localization, and functional expression of RT a voltage-gated sodium channel from human brain."; RL Proc. Natl. Acad. Sci. U.S.A. 89:8220-8224(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2). RX PubMed=11245985; DOI=10.1016/s0378-1119(00)00594-1; RA Kasai N., Fukushima K., Ueki Y., Prasad S., Nosakowski J., Sugata K., RA Sugata A., Nishizaki K., Meyer N.C., Smith R.J.H.; RT "Genomic structures of SCN2A and SCN3A -- candidate genes for deafness at RT the DFNA16 locus."; RL Gene 264:113-122(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89. RA Lu C.-M., Eichelberger J.S., Beckman M.L., Schade S.D., Brown G.B.; RT "Isolation of the 5'-flanking region for human brain sodium channel subtype RT II alpha-Subunit (SCN2A)."; RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1709-1994. RC TISSUE=Brain; RX PubMed=1317301; DOI=10.1016/0014-5793(92)80476-w; RA Lu C.-M., Han J., Rado T.A., Brown G.B.; RT "Differential expression of two sodium channel subtypes in human brain."; RL FEBS Lett. 303:53-58(1992). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1702-1772. RX PubMed=1846440; DOI=10.1073/pnas.88.2.335; RA Han J., Lu C.-M., Brown G.B., Rado T.A.; RT "Direct amplification of a single dissected chromosomal segment by RT polymerase chain reaction: a human brain sodium channel gene is on RT chromosome 2q22-q23."; RL Proc. Natl. Acad. Sci. U.S.A. 88:335-339(1991). RN [7] RP INTERACTION WITH SCN4B. RX PubMed=24297919; DOI=10.1073/pnas.1314557110; RA Gilchrist J., Das S., Van Petegem F., Bosmans F.; RT "Crystallographic insights into sodium-channel modulation by the beta4 RT subunit."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E5016-E5024(2013). RN [8] RP SUBUNIT, AND 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 [9] RP SUBUNIT, INTERACTION WITH THE SPIDER PROTOXIN-II, AND DISULFIDE BOND. RX PubMed=26894959; DOI=10.7554/elife.10960; RA Das S., Gilchrist J., Bosmans F., Van Petegem F.; RT "Binary architecture of the Nav1.2-beta2 signaling complex."; RL Elife 5:0-0(2016). RN [10] RP INVOLVEMENT IN EA9, VARIANTS EA9 VAL-263; ALA-1522 AND GLY-1882, AND RP CHARACTERIZATION OF VARIANTS EA9 ALA-1522 AND GLY-1882. RX PubMed=26645390; DOI=10.1007/s00415-015-7984-0; RA Schwarz N., Hahn A., Bast T., Mueller S., Loeffler H., Maljevic S., RA Gaily E., Prehl I., Biskup S., Joensuu T., Lehesjoki A.E., Neubauer B.A., RA Lerche H., Hedrich U.B.; RT "Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with RT late-onset episodic ataxia."; RL J. Neurol. 263:334-343(2016). RN [11] RP SUBUNIT, AND INTERACTION WITH THE SPIDER BETA/DELTA-THERAPHOTOXIN-PRE1A. RX PubMed=28428547; DOI=10.1038/s41598-017-01129-0; RA Wingerd J.S., Mozar C.A., Ussing C.A., Murali S.S., Chin Y.K., RA Cristofori-Armstrong B., Durek T., Gilchrist J., Vaughan C.W., Bosmans F., RA Adams D.J., Lewis R.J., Alewood P.F., Mobli M., Christie M.J., Rash L.D.; RT "The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance of the RT S1-S2 voltage-sensor region for sodium channel subtype selectivity."; RL Sci. Rep. 7:974-988(2017). RN [12] 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 [13] RP STRUCTURE BY ELECTRON MICROSCOPY (3.0 ANGSTROMS) IN COMPLEX WITH SCN2B AND RP MU-CONOTOXIN KIIIA, SUBUNIT, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-340; RP ASN-1368; ASN-1382 AND ASN-1393. RX PubMed=30765605; DOI=10.1126/science.aaw2999; RA Pan X., Li Z., Huang X., Huang G., Gao S., Shen H., Liu L., Lei J., Yan N.; RT "Molecular basis for pore blockade of human Na+ channel Nav1.2 by the mu- RT conotoxin KIIIA."; RL Science 363:1309-1313(2019). RN [14] RP VARIANT HIS-1918. RX PubMed=11738931; DOI=10.1016/s0920-1211(01)00312-6; RA Haug K., Hallmann K., Rebstock J., Dullinger J., Muth S., Haverkamp F., RA Pfeiffer H., Rau B., Elger C.E., Propping P., Heils A.; RT "The voltage-gated sodium channel gene SCN2A and idiopathic generalized RT epilepsy."; RL Epilepsy Res. 47:243-246(2001). RN [15] RP VARIANT BFIS3 TRP-188, CHARACTERIZATION OF VARIANT BFIS3 TRP-188, AND RP VARIANTS LYS-19 AND GLN-524. RX PubMed=11371648; DOI=10.1073/pnas.111065098; RA Sugawara T., Tsurubuchi Y., Agarwala K.L., Ito M., Fukuma G., RA Mazaki-Miyazaki E., Nagafuji H., Noda M., Imoto K., Wada K., Mitsudome A., RA Kaneko S., Montal M., Nagata K., Hirose S., Yamakawa K.; RT "A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a RT patient with febrile and afebrile seizures causes channel dysfunction."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6384-6389(2001). RN [16] RP ERRATUM OF PUBMED:11371648. RA Sugawara T., Tsurubuchi Y., Agarwala K.L., Ito M., Fukuma G., RA Mazaki-Miyazaki E., Nagafuji H., Noda M., Imoto K., Wada K., Mitsudome A., RA Kaneko S., Montal M., Nagata K., Hirose S., Yamakawa K.; RL Proc. Natl. Acad. Sci. U.S.A. 98:10515-10515(2001). RN [17] RP VARIANTS BFIS3 PHE-1330 AND VAL-1563. RX PubMed=12243921; DOI=10.1016/s0140-6736(02)09968-3; RA Heron S.E., Crossland K.M., Andermann E., Phillips H.A., Hall A.J., RA Bleasel A., Shevell M., Mercho S., Seni M.H., Guiot M.C., Mulley J.C., RA Berkovic S.F., Scheffer I.E.; RT "Sodium-channel defects in benign familial neonatal-infantile seizures."; RL Lancet 360:851-852(2002). RN [18] RP ERRATUM OF PUBMED:12243921. RA Heron S.E., Crossland K.M., Andermann E., Phillips H.A., Hall A.J., RA Bleasel A., Shevell M., Mercho S., Seni M.H., Guiot M.C., Mulley J.C., RA Berkovic S.F., Scheffer I.E.; RL Lancet 360:1520-1520(2002). RN [19] RP VARIANTS LYS-19 AND THR-1902. RX PubMed=12610651; DOI=10.1038/sj.mp.4001241; RA Weiss L.A., Escayg A., Kearney J.A., Trudeau M., MacDonald B.T., Mori M., RA Reichert J., Buxbaum J.D., Meisler M.H.; RT "Sodium channels SCN1A, SCN2A and SCN3A in familial autism."; RL Mol. Psychiatry 8:186-194(2003). RN [20] RP VARIANTS BFIS3 GLN-223; ILE-892; ILE-1003 AND GLN-1319. RX PubMed=15048894; DOI=10.1002/ana.20029; RA Berkovic S.F., Heron S.E., Giordano L., Marini C., Guerrini R., RA Kaplan R.E., Gambardella A., Steinlein O.K., Grinton B.E., Dean J.T., RA Bordo L., Hodgson B.L., Yamamoto T., Mulley J.C., Zara F., Scheffer I.E.; RT "Benign familial neonatal-infantile seizures: characterization of a new RT sodium channelopathy."; RL Ann. Neurol. 55:550-557(2004). RN [21] RP VARIANT 102-ARG--LYS-2005 DEL, AND CHARACTERIZATION OF VARIANT RP 102-ARG--LYS-2005 DEL. RX PubMed=15028761; DOI=10.1523/jneurosci.3089-03.2004; RA Kamiya K., Kaneda M., Sugawara T., Mazaki E., Okamura N., Montal M., RA Makita N., Tanaka M., Fukushima K., Fujiwara T., Inoue Y., Yamakawa K.; RT "A nonsense mutation of the sodium channel gene SCN2A in a patient with RT intractable epilepsy and mental decline."; RL J. Neurosci. 24:2690-2698(2004). RN [22] RP VARIANT VAL-328. RX PubMed=16122630; DOI=10.1016/j.braindev.2004.11.005; RA Kimura K., Sugawara T., Mazaki-Miyazaki E., Hoshino K., Nomura Y., RA Tateno A., Hachimori K., Yamakawa K., Segawa M.; RT "A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in RT infancy (SMEI) inherited from a father with febrile seizures."; RL Brain Dev. 27:424-430(2005). RN [23] RP VARIANT BFIS3 LYS-1001. RX PubMed=16417554; DOI=10.1111/j.1528-1167.2006.00392.x; RA Striano P., Bordo L., Lispi M.L., Specchio N., Minetti C., Vigevano F., RA Zara F.; RT "A novel SCN2A mutation in family with benign familial infantile RT seizures."; RL Epilepsia 47:218-220(2006). RN [24] RP CHARACTERIZATION OF VARIANTS BFIS3 GLN-223; GLN-1319; PHE-1330 AND RP VAL-1563, FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=17021166; DOI=10.1523/jneurosci.2476-06.2006; RA Scalmani P., Rusconi R., Armatura E., Zara F., Avanzini G., RA Franceschetti S., Mantegazza M.; RT "Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel RT causing benign familial neonatal-infantile seizures."; RL J. Neurosci. 26:10100-10109(2006). RN [25] RP VARIANTS BFIS3 GLN-430 AND SER-1596. RX PubMed=17386050; DOI=10.1111/j.1528-1167.2007.01049.x; RA Herlenius E., Heron S.E., Grinton B.E., Keay D., Scheffer I.E., RA Mulley J.C., Berkovic S.F.; RT "SCN2A mutations and benign familial neonatal-infantile seizures: the RT phenotypic spectrum."; RL Epilepsia 48:1138-1142(2007). RN [26] RP CHARACTERIZATION OF VARIANTS BFIS3 GLN-1319; PHE-1330 AND VAL-1563. RX PubMed=18479388; DOI=10.1111/j.1528-1167.2008.01619.x; RA Misra S.N., Kahlig K.M., George A.L. Jr.; RT "Impaired NaV1.2 function and reduced cell surface expression in benign RT familial neonatal-infantile seizures."; RL Epilepsia 49:1535-1545(2008). RN [27] RP VARIANTS ASN-322 AND VAL-328, AND VARIANT DEE11 THR-1312. RX PubMed=19783390; DOI=10.1016/j.braindev.2009.08.009; RA Shi X., Yasumoto S., Nakagawa E., Fukasawa T., Uchiya S., Hirose S.; RT "Missense mutation of the sodium channel gene SCN2A causes Dravet RT syndrome."; RL Brain Dev. 31:758-762(2009). RN [28] RP VARIANTS DEE11 LYS-1211 AND MET-1473, VARIANTS LYS-19; VAL-328; GLN-524 AND RP VAL-575, CHARACTERIZATION OF VARIANTS DEE11 LYS-1211 AND MET-1473, AND RP CHARACTERIZATION OF VARIANT VAL-575. RX PubMed=19786696; DOI=10.1212/wnl.0b013e3181b9cebc; RA Ogiwara I., Ito K., Sawaishi Y., Osaka H., Mazaki E., Inoue I., Montal M., RA Hashikawa T., Shike T., Fujiwara T., Inoue Y., Kaneda M., Yamakawa K.; RT "De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in RT intractable epilepsies."; RL Neurology 73:1046-1053(2009). RN [29] RP VARIANTS BFIS3 VAL-252 AND MET-261, AND CHARACTERIZATION OF VARIANTS BFIS3 RP VAL-252 AND MET-261. RX PubMed=20371507; DOI=10.1093/brain/awq057; RA Liao Y., Deprez L., Maljevic S., Pitsch J., Claes L., Hristova D., RA Jordanova A., Ala-Mello S., Bellan-Koch A., Blazevic D., Schubert S., RA Thomas E.A., Petrou S., Becker A.J., De Jonghe P., Lerche H.; RT "Molecular correlates of age-dependent seizures in an inherited neonatal- RT infantile epilepsy."; RL Brain 133:1403-1414(2010). RN [30] RP VARIANT DEE11 VAL-263, AND CHARACTERIZATION OF VARIANT DEE11 VAL-263. RX PubMed=20956790; DOI=10.1212/wnl.0b013e3181f8812e; RA Liao Y., Anttonen A.K., Liukkonen E., Gaily E., Maljevic S., Schubert S., RA Bellan-Koch A., Petrou S., Ahonen V.E., Lerche H., Lehesjoki A.E.; RT "SCN2A mutation associated with neonatal epilepsy, late-onset episodic RT ataxia, myoclonus, and pain."; RL Neurology 75:1454-1458(2010). RN [31] RP VARIANT BFIS3 GLU-208. RX PubMed=22612257; DOI=10.1111/j.1528-1167.2012.03516.x; RA Lemke J.R., Riesch E., Scheurenbrand T., Schubach M., Wilhelm C., RA Steiner I., Hansen J., Courage C., Gallati S., Buerki S., Strozzi S., RA Simonetti B.G., Grunt S., Steinlin M., Alber M., Wolff M., Klopstock T., RA Prott E.C., Lorenz R., Spaich C., Rona S., Lakshminarasimhan M., Kroell J., RA Dorn T., Kraemer G., Synofzik M., Becker F., Weber Y.G., Lerche H., RA Boehm D., Biskup S.; RT "Targeted next generation sequencing as a diagnostic tool in epileptic RT disorders."; RL Epilepsia 53:1387-1398(2012). RN [32] RP VARIANT THR-1128. RX PubMed=22591750; DOI=10.1016/j.eplepsyres.2012.04.016; RA Kobayashi K., Ohzono H., Shinohara M., Saitoh M., Ohmori I., Ohtsuka Y., RA Mizuguchi M.; RT "Acute encephalopathy with a novel point mutation in the SCN2A gene."; RL Epilepsy Res. 102:109-112(2012). RN [33] RP VARIANTS LYS-19; ASN-322; VAL-328 AND ASN-649, AND VARIANT DEE11 THR-1312. RX PubMed=23195492; DOI=10.1016/j.eplepsyres.2012.06.006; RA Wang J.W., Shi X.Y., Kurahashi H., Hwang S.K., Ishii A., Higurashi N., RA Kaneko S., Hirose S.; RT "Prevalence of SCN1A mutations in children with suspected Dravet syndrome RT and intractable childhood epilepsy."; RL Epilepsy Res. 102:195-200(2012). RN [34] RP CHARACTERIZATION OF VARIANT DEE11 THR-1312. RX PubMed=22677033; DOI=10.1016/j.nbd.2012.05.017; RA Lossin C., Shi X., Rogawski M.A., Hirose S.; RT "Compromised function in the Na(v)1.2 Dravet syndrome mutation R1312T."; RL Neurobiol. Dis. 47:378-384(2012). RN [35] RP VARIANT DEE11 1398-TRP--LYS-2005 DEL. RX PubMed=23033978; DOI=10.1056/nejmoa1206524; RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., RA Veltman J.A., Vissers L.E.; RT "Diagnostic exome sequencing in persons with severe intellectual RT disability."; RL N. Engl. J. Med. 367:1921-1929(2012). RN [36] RP VARIANT DEE11 VAL-263. RX PubMed=23550958; DOI=10.1111/epi.12137; RA Touma M., Joshi M., Connolly M.C., Grant P.E., Hansen A.R., Khwaja O., RA Berry G.T., Kinney H.C., Poduri A., Agrawal P.B.; RT "Whole genome sequencing identifies SCN2A mutation in monozygotic twins RT with Ohtahara syndrome and unique neuropathologic findings."; RL Epilepsia 54:E81-E85(2013). RN [37] RP VARIANT BFIS3 CYS-1589, AND CHARACTERIZATION OF VARIANT BFIS3 CYS-1589. RX PubMed=23758435; DOI=10.1111/epi.12241; RA Lauxmann S., Boutry-Kryza N., Rivier C., Mueller S., Hedrich U.B., RA Maljevic S., Szepetowski P., Lerche H., Lesca G.; RT "An SCN2A mutation in a family with infantile seizures from Madagascar RT reveals an increased subthreshold Na(+) current."; RL Epilepsia 54:E117-E121(2013). RN [38] RP VARIANTS BFIS3 GLN-223; LYS-1001; GLN-1319 AND ASN-1641. RX PubMed=23360469; DOI=10.1111/epi.12089; RA Zara F., Specchio N., Striano P., Robbiano A., Gennaro E., Paravidino R., RA Vanni N., Beccaria F., Capovilla G., Bianchi A., Caffi L., Cardilli V., RA Darra F., Bernardina B.D., Fusco L., Gaggero R., Giordano L., Guerrini R., RA Incorpora G., Mastrangelo M., Spaccini L., Laverda A.M., Vecchi M., RA Vanadia F., Veggiotti P., Viri M., Occhi G., Budetta M., Taglialatela M., RA Coviello D.A., Vigevano F., Minetti C.; RT "Genetic testing in benign familial epilepsies of the first year of life: RT clinical and diagnostic significance."; RL Epilepsia 54:425-436(2013). RN [39] RP VARIANT DEE11 ASP-211. RX PubMed=23662938; DOI=10.1111/epi.12203; RA Kodera H., Kato M., Nord A.S., Walsh T., Lee M., Yamanaka G., Tohyama J., RA Nakamura K., Nakagawa E., Ikeda T., Ben-Zeev B., Lev D., Lerman-Sagie T., RA Straussberg R., Tanabe S., Ueda K., Amamoto M., Ohta S., Nonoda Y., RA Nishiyama K., Tsurusaki Y., Nakashima M., Miyake N., Hayasaka K., RA King M.C., Matsumoto N., Saitsu H.; RT "Targeted capture and sequencing for detection of mutations causing early RT onset epileptic encephalopathy."; RL Epilepsia 54:1262-1269(2013). RN [40] RP VARIANTS DEE11 ILE-136; ASN-905; CYS-928 AND GLN-1882. RX PubMed=23708187; DOI=10.1038/ng.2646; RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J., RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G., RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T., RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N., RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L., RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.; RT "Targeted resequencing in epileptic encephalopathies identifies de novo RT mutations in CHD2 and SYNGAP1."; RL Nat. Genet. 45:825-830(2013). RN [41] RP VARIANTS DEE11 GLY-169; ASP-212; ASP-213; SER-236; THR-263; GLN-853; RP THR-876; LYS-999; VAL-1323; LEU-1326; TYR-1336; THR-1338; ASN-1623 AND RP LEU-1629. RX PubMed=23935176; DOI=10.1212/wnl.0b013e3182a43e57; RA Nakamura K., Kato M., Osaka H., Yamashita S., Nakagawa E., Haginoya K., RA Tohyama J., Okuda M., Wada T., Shimakawa S., Imai K., Takeshita S., RA Ishiwata H., Lev D., Lerman-Sagie T., Cervantes-Barragan D.E., RA Villarroel C.E., Ohfu M., Writzl K., Gnidovec Strazisar B., Hirabayashi S., RA Chitayat D., Myles Reid D., Nishiyama K., Kodera H., Nakashima M., RA Tsurusaki Y., Miyake N., Hayasaka K., Matsumoto N., Saitsu H.; RT "Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome."; RL Neurology 81:992-998(2013). RN [42] RP VARIANT GLU-1422. RX PubMed=23827426; DOI=10.1016/j.pediatrneurol.2013.03.002; RA Sundaram S.K., Chugani H.T., Tiwari V.N., Huq A.H.; RT "SCN2A mutation is associated with infantile spasms and bitemporal glucose RT hypometabolism."; RL Pediatr. Neurol. 49:46-49(2013). RN [43] RP VARIANT DEE11 ASP-1326. RX PubMed=23988467; DOI=10.1016/j.pediatrneurol.2013.07.004; RA Dhamija R., Wirrell E., Falcao G., Kirmani S., Wong-Kisiel L.C.; RT "Novel de novo SCN2A mutation in a child with migrating focal seizures of RT infancy."; RL Pediatr. Neurol. 49:486-488(2013). RN [44] RP VARIANT DEE11 LEU-1882. RX PubMed=24579881; DOI=10.1111/epi.12554; RA Baasch A.L., Huening I., Gilissen C., Klepper J., Veltman J.A., RA Gillessen-Kaesbach G., Hoischen A., Lohmann K.; RT "Exome sequencing identifies a de novo SCN2A mutation in a patient with RT intractable seizures, severe intellectual disability, optic atrophy, RT muscular hypotonia, and brain abnormalities."; RL Epilepsia 55:E25-E29(2014). RN [45] RP VARIANTS DEE11 LYS-132; GLY-430 AND PRO-1342. RX PubMed=24659627; DOI=10.1684/epd.2014.0641; RA Matalon D., Goldberg E., Medne L., Marsh E.D.; RT "Confirming an expanded spectrum of SCN2A mutations: a case series."; RL Epileptic Disord. 16:13-18(2014). RN [46] RP VARIANT DEE11 ARG-1853. RX PubMed=24463883; DOI=10.1093/hmg/ddu030; RG WGS500 Consortium; RA Martin H.C., Kim G.E., Pagnamenta A.T., Murakami Y., Carvill G.L., RA Meyer E., Copley R.R., Rimmer A., Barcia G., Fleming M.R., Kronengold J., RA Brown M.R., Hudspith K.A., Broxholme J., Kanapin A., Cazier J.B., RA Kinoshita T., Nabbout R., Bentley D., McVean G., Heavin S., Zaiwalla Z., RA McShane T., Mefford H.C., Shears D., Stewart H., Kurian M.A., RA Scheffer I.E., Blair E., Donnelly P., Kaczmarek L.K., Taylor J.C.; RT "Clinical whole-genome sequencing in severe early-onset epilepsy reveals RT new genes and improves molecular diagnosis."; RL Hum. Mol. Genet. 23:3200-3211(2014). RN [47] RP VARIANT DEE11 PRO-1342. RX PubMed=24710820; DOI=10.1055/s-0034-1372302; RA Hackenberg A., Baumer A., Sticht H., Schmitt B., Kroell-Seger J., Wille D., RA Joset P., Papuc S., Rauch A., Plecko B.; RT "Infantile epileptic encephalopathy, transient choreoathetotic movements, RT and hypersomnia due to a De Novo missense mutation in the SCN2A gene."; RL Neuropediatrics 45:261-264(2014). RN [48] RP VARIANT DEE11 GLN-853. RX PubMed=25772804; DOI=10.1007/s13760-015-0454-8; RA Samanta D., Ramakrishnaiah R.; RT "De novo R853Q mutation of SCN2A gene and West syndrome."; RL Acta Neurol. Belg. 115:773-776(2015). RN [49] RP VARIANT DEE11 TRP-1660. RX PubMed=25457084; DOI=10.1016/j.braindev.2014.10.001; RA Fukasawa T., Kubota T., Negoro T., Saitoh M., Mizuguchi M., Ihara Y., RA Ishii A., Hirose S.; RT "A case of recurrent encephalopathy with SCN2A missense mutation."; RL Brain Dev. 37:631-634(2015). RN [50] RP VARIANT DEE11 LYS-1211. RX PubMed=25459969; DOI=10.1016/j.braindev.2014.10.008; RA Wong V.C., Fung C.W., Kwong A.K.; RT "SCN2A mutation in a Chinese boy with infantile spasm - response to RT Modified Atkins Diet."; RL Brain Dev. 37:729-732(2015). RN [51] RP VARIANTS DEE11 GLY-220 AND ALA-1522. RX PubMed=25818041; DOI=10.1111/epi.12954; RA Mercimek-Mahmutoglu S., Patel J., Cordeiro D., Hewson S., Callen D., RA Donner E.J., Hahn C.D., Kannu P., Kobayashi J., Minassian B.A., Moharir M., RA Siriwardena K., Weiss S.K., Weksberg R., Snead O.C. III; RT "Diagnostic yield of genetic testing in epileptic encephalopathy in RT childhood."; RL Epilepsia 56:707-716(2015). RN [52] RP VARIANTS BFIS3 LYS-1321 AND LYS-1531. RX PubMed=25982755; DOI=10.1111/epi.13020; RA Grinton B.E., Heron S.E., Pelekanos J.T., Zuberi S.M., Kivity S., Afawi Z., RA Williams T.C., Casalaz D.M., Yendle S., Linder I., Lev D., Lerman-Sagie T., RA Malone S., Bassan H., Goldberg-Stern H., Stanley T., Hayman M., Calvert S., RA Korczyn A.D., Shevell M., Scheffer I.E., Mulley J.C., Berkovic S.F.; RT "Familial neonatal seizures in 36 families: Clinical and genetic features RT correlate with outcome."; RL Epilepsia 56:1071-1080(2015). RN [53] RP VARIANTS VAL-172 AND VAL-328. RX PubMed=26311622; DOI=10.1016/j.eplepsyres.2015.08.001; RA Saitoh M., Ishii A., Ihara Y., Hoshino A., Terashima H., Kubota M., RA Kikuchi K., Yamanaka G., Amemiya K., Hirose S., Mizuguchi M.; RT "Missense mutations in sodium channel SCN1A and SCN2A predispose children RT to encephalopathy with severe febrile seizures."; RL Epilepsy Res. 117:1-6(2015). RN [54] RP VARIANTS 583-ARG--LYS-2005 DEL AND ARG-1372. RX PubMed=25969726; DOI=10.1186/s13229-015-0017-0; RA Codina-Sola M., Rodriguez-Santiago B., Homs A., Santoyo J., Rigau M., RA Aznar-Lain G., Del Campo M., Gener B., Gabau E., Botella M.P., RA Gutierrez-Arumi A., Antinolo G., Perez-Jurado L.A., Cusco I.; RT "Integrated analysis of whole-exome sequencing and transcriptome profiling RT in males with autism spectrum disorders."; RL Mol. Autism 6:21-21(2015). RN [55] RP VARIANTS DEE11 ILE-136; LYS-218; LEU-856; ASN-905; CYS-928; ARG-1593; RP VAL-1634 AND GLN-1882, VARIANT BFIS3 SER-240, AND VARIANT LYS-976. RX PubMed=26291284; DOI=10.1212/wnl.0000000000001926; RA Howell K.B., McMahon J.M., Carvill G.L., Tambunan D., Mackay M.T., RA Rodriguez-Casero V., Webster R., Clark D., Freeman J.L., Calvert S., RA Olson H.E., Mandelstam S., Poduri A., Mefford H.C., Harvey A.S., RA Scheffer I.E.; RT "SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating RT focal seizures."; RL Neurology 85:958-966(2015). RN [56] RP VARIANTS LYS-674; 1515-ARG--LYS-2005 DEL AND ARG-1744. RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009; RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T., RA Sestan N., Walsh C.A.; RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates RT Multiple Genetic Mechanisms."; RL Neuron 88:910-917(2015). RN [57] RP VARIANT DEE11 PRO-1342. RX PubMed=26138355; DOI=10.1111/cge.12636; RA Dimassi S., Labalme A., Ville D., Calender A., Mignot C., Boutry-Kryza N., RA de Bellescize J., Rivier-Ringenbach C., Bourel-Ponchel E., Cheillan D., RA Simonet T., Maincent K., Rossi M., Till M., Mougou-Zerelli S., Edery P., RA Saad A., Heron D., des Portes V., Sanlaville D., Lesca G.; RT "Whole-exome sequencing improves the diagnosis yield in sporadic infantile RT spasm syndrome."; RL Clin. Genet. 89:198-204(2016). RN [58] RP VARIANT EA9 ASP-1634. RX PubMed=27328862; DOI=10.1016/j.ejpn.2016.05.020; RA Leach E.L., van Karnebeek C.D., Townsend K.N., Tarailo-Graovac M., RA Hukin J., Gibson W.T.; RT "Episodic ataxia associated with a de novo SCN2A mutation."; RL Eur. J. Paediatr. Neurol. 20:772-776(2016). RN [59] RP VARIANTS DEE11 MET-873; ILE-987; LYS-999; VAL-999; GLN-1260; GLU-1260; RP 1435-ARG--LYS-2005 DEL; PRO-1479; PRO-1650; PHE-1829 AND GLN-1882. RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263; RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A., RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A., RA Scott R.H.; RT "Improving diagnosis and broadening the phenotypes in early-onset seizure RT and severe developmental delay disorders through gene panel analysis."; RL J. Med. Genet. 53:310-317(2016). RN [60] RP VARIANT EA9 VAL-263. RX PubMed=27159988; DOI=10.1007/s00415-016-8149-5; RA Johannesen K.M., Miranda M.J., Lerche H., Moeller R.S.; RT "Letter to the editor: confirming neonatal seizure and late onset ataxia in RT SCN2A Ala263Val."; RL J. Neurol. 263:1459-1460(2016). RN [61] RP VARIANTS LYS-19; 169-GLU--LYS-2005 DEL; PRO-850; ARG-908; PHE-1282; RP VAL-1559 AND ALA-1823. RX PubMed=26555645; DOI=10.1097/ypg.0000000000000110; RA Carroll L.S., Woolf R., Ibrahim Y., Williams H.J., Dwyer S., Walters J., RA Kirov G., O'Donovan M.C., Owen M.J.; RT "Mutation screening of SCN2A in schizophrenia and identification of a novel RT loss-of-function mutation."; RL Psychiatr. Genet. 26:60-65(2016). RN [62] RP VARIANTS ASN-12; GLY-82; HIS-379; CYS-937; HIS-937; 959-CYS--LYS-2005 DEL; RP 1013-GLY--LYS-2005 DEL; ARG-1386 AND MET-1420, CHARACTERIZATION OF VARIANTS RP ASN-12; GLY-82; HIS-379; CYS-937; HIS-937; 959-CYS--LYS-2005 DEL; RP 1013-GLY--LYS-2005 DEL; ARG-1386 AND MET-1420, INVOLVEMENT IN AUTISM RP SPECTRUM DISORDER, FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=28256214; DOI=10.1016/j.biopsych.2017.01.009; RA Ben-Shalom R., Keeshen C.M., Berrios K.N., An J.Y., Sanders S.J., RA Bender K.J.; RT "Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A RT Variants Observed in Individuals With Autism Spectrum Disorder or Infantile RT Seizures."; RL Biol. Psychiatry 82:224-232(2017). RN [63] RP VARIANT MET-424. RX PubMed=28709814; DOI=10.1016/j.braindev.2017.06.003; RA Liang J.S., Lin L.J., Yang M.T., Wang J.S., Lu J.F.; RT "The therapeutic implication of a novel SCN2A mutation associated early- RT onset epileptic encephalopathy with Rett-like features."; RL Brain Dev. 39:877-881(2017). RN [64] RP VARIANT GLY-191, AND VARIANTS DEE11 ILE-251; VAL-263; VAL-896; VAL-1316; RP VAL-1323; TYR-1344; THR-1548 AND GLN-1882. RX PubMed=27864847; DOI=10.1002/humu.23149; RG Clinical Study Group; RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D., RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S., RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.; RT "Diagnostic targeted resequencing in 349 patients with drug-resistant RT pediatric epilepsies identifies causative mutations in 30 different RT genes."; RL Hum. Mutat. 38:216-225(2017). RN [65] RP VARIANT EA9 VAL-263. RX PubMed=28065826; DOI=10.1016/j.pediatrneurol.2016.11.008; RA Gorman K.M., King M.D.; RT "SCN2A p.Ala263Val Variant a Phenotype of Neonatal Seizures Followed by RT Paroxysmal Ataxia in Toddlers."; RL Pediatr. Neurol. 67:111-112(2017). RN [66] RP VARIANT DEE11 ILE-136. RX PubMed=30415926; DOI=10.1016/j.braindev.2018.10.015; RA Turkdogan D., Thomas G., Demirel B.; RT "Ketogenic diet as a successful early treatment modality for SCN2A RT mutation."; RL Brain Dev. 41:389-391(2019). RN [67] RP VARIANT DEE11 CYS-191. RX PubMed=29625812; DOI=10.1016/j.braindev.2018.03.005; RA Su D.J., Lu J.F., Lin L.J., Liang J.S., Hung K.L.; RT "SCN2A mutation in an infant presenting with migrating focal seizures and RT infantile spasm responsive to a ketogenic diet."; RL Brain Dev. 40:724-727(2018). RN [68] RP VARIANT THR-467, AND INVOLVEMENT IN DISEASE. RX PubMed=29635106; DOI=10.1016/j.clineuro.2017.10.020; RA Liu X.W., Li W., Han T., Wei K., Qiao S., Su L., Chi Z.; RT "The finding of a new heterozygous mutation site of the SCN2A gene in a RT monozygotic twin family carrying and exhibiting genetic epilepsy with RT febrile seizures plus (GEFS+) using targeted next-generation sequencing."; RL Clin. Neurol. Neurosurg. 169:86-91(2018). RN [69] RP VARIANT ARG-1460. RX PubMed=30062040; DOI=10.1038/s41439-018-0019-5; RA Yokoi T., Enomoto Y., Tsurusaki Y., Naruto T., Kurosawa K.; RT "Nonsyndromic intellectual disability with novel heterozygous SCN2A RT mutation and epilepsy."; RL Hum. Genome Var. 5:20-20(2018). RN [70] RP VARIANTS BFIS3 GLU-208 AND GLU-908, CHARACTERIZATION OF VARIANTS BFIS3 RP GLU-208 AND GLU-908, VARIANT DEE11 ILE-773, AND CHARACTERIZATION OF VARIANT RP DEE11 ILE-773. RX PubMed=30144217; DOI=10.1002/humu.23619; RA Lauxmann S., Verbeek N.E., Liu Y., Zaichuk M., Mueller S., Lemke J.R., RA van Kempen M.J.A., Lerche H., Hedrich U.B.S.; RT "Relationship of electrophysiological dysfunction and clinical severity in RT SCN2A-related epilepsies."; RL Hum. Mutat. 39:1942-1956(2018). RN [71] RP VARIANT PRO-1650. RX PubMed=30165711; DOI=10.1055/s-0038-1668141; RA Fazeli W., Becker K., Herkenrath P., Duechting C., Koerber F., Landgraf P., RA Nuernberg P., Altmueller J., Thiele H., Koy A., Liebau M.C., Simon T., RA Doetsch J., Cirak S.; RT "Dominant SCN2A Mutation Causes Familial Episodic Ataxia and Impairment of RT Speech Development."; RL Neuropediatrics 49:379-384(2018). RN [72] RP VARIANTS DEE11 GLN-853 AND GLN-1882, CHARACTERIZATION OF VARIANTS DEE11 RP GLN-853 AND GLN-1882, VARIANT BFIS3 VAL-1563, CHARACTERIZATION OF VARIANT RP BFIS3 VAL-1563, FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=29844171; DOI=10.1073/pnas.1800077115; RA Berecki G., Howell K.B., Deerasooriya Y.H., Cilio M.R., Oliva M.K., RA Kaplan D., Scheffer I.E., Berkovic S.F., Petrou S.; RT "Dynamic action potential clamp predicts functional separation in mild RT familial and severe de novo forms of SCN2A epilepsy."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E5516-E5525(2018). CC -!- FUNCTION: Mediates the voltage-dependent sodium ion permeability of CC excitable membranes. Assuming opened or closed conformations in CC response to the voltage difference across the membrane, the protein CC forms a sodium-selective channel through which Na(+) ions may pass in CC accordance with their electrochemical gradient (PubMed:1325650, CC PubMed:17021166, PubMed:28256214, PubMed:29844171). Implicated in the CC regulation of hippocampal replay occurring within sharp wave ripples CC (SPW-R) important for memory (By similarity). CC {ECO:0000250|UniProtKB:B1AWN6, ECO:0000269|PubMed:1325650, CC ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:28256214, CC ECO:0000269|PubMed:29844171}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:1325650, CC ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:28256214, CC ECO:0000269|PubMed:29844171}; CC -!- SUBUNIT: Heterooligomer of a large alpha subunit and a smaller beta CC subunit. Heterooligomer with SCN2B or SCN4B; disulfide-linked. CC Heterooligomer with SCN1B or SCN3B; non-covalently linked. Interacts CC with NEDD4L. Interacts with CALM. Interacts with TMEM233 CC (PubMed:37117223). Interacts with the conotoxin GVIIJ CC (PubMed:24497506). Interacts with the spider beta/delta-theraphotoxin- CC Pre1a (PubMed:28428547). Interacts with the conotoxin KIIIA CC (PubMed:30765605). Interacts with the spider protoxin-II CC (PubMed:26894959). {ECO:0000269|PubMed:24297919, CC ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:28428547, CC ECO:0000269|PubMed:30765605, ECO:0000305|PubMed:37117223}. CC -!- INTERACTION: CC Q99250; P62158: CALM3; NbExp=3; IntAct=EBI-724872, EBI-397435; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1325650, CC ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:29844171}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Adult, 6A; CC IsoId=Q99250-1; Sequence=Displayed; CC Name=2; Synonyms=Neonatal, 6N; CC IsoId=Q99250-2; Sequence=VSP_001032; 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}. CC -!- PTM: May be ubiquitinated by NEDD4L; which would promote its CC endocytosis. {ECO:0000250}. CC -!- PTM: Phosphorylation at Ser-1506 by PKC in a highly conserved CC cytoplasmic loop slows inactivation of the sodium channel and reduces CC peak sodium currents. {ECO:0000250}. CC -!- PTM: Sumoylated at Lys-38. Sumoylation is induced by hypoxia, increases CC voltage-gated sodium current and mediates the early response to acute CC hypoxia in neurons. Sumoylated SCN2A is located at the cell membrane. CC {ECO:0000250|UniProtKB:P04775}. CC -!- DISEASE: Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: A CC form of benign familial infantile epilepsy, a neurologic disorder CC characterized by afebrile seizures occurring in clusters during the CC first year of life, without neurologic sequelae. BFIS3 inheritance is CC autosomal dominant. {ECO:0000269|PubMed:11371648, CC ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, CC ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, CC ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, CC ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, CC ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, CC ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284, CC ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 11 (DEE11) CC [MIM:613721]: An autosomal dominant seizure disorder characterized by CC neonatal or infantile onset of refractory seizures with resultant CC delayed neurologic development and persistent neurologic abnormalities. CC Patients may progress to West syndrome, which is characterized by tonic CC spasms with clustering, arrest of psychomotor development, and CC hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, CC ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, CC ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, CC ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, CC ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, CC ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, CC ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, CC ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, CC ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, CC ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, CC ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, CC ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, CC ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, CC ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=Defects in SCN2A are associated with genetic epilepsy CC with febrile seizures plus (GEFS+), a familial autosomal dominant CC epilepsy syndrome, a clinical subset of febrile seizures, characterized CC by frequent episodes after 6 years of age and various types of CC subsequent epilepsy. {ECO:0000269|PubMed:29635106}. CC -!- DISEASE: Note=Defects in SCN2A are associated with autism spectrum CC disorders (ASD). It seems that mutations resulting in sodium channel CC gain of function and increased neuron excitability lead to infantile CC seizures, whereas variants resulting in sodium channel loss of function CC and decrease neuron excitability are associated with ASD. CC {ECO:0000269|PubMed:28256214}. CC -!- DISEASE: Episodic ataxia 9 (EA9) [MIM:618924]: An autosomal dominant CC neurologic disorder characterized by episodic ataxia manifesting in the CC first years of life, early-onset seizures, difficulty walking, CC dizziness, slurred speech, headache, vomiting, and pain. The duration CC of ataxic episodes is heterogeneous. Most patients show episodes CC lasting minutes to maximum several hours, but periods lasting days up CC to weeks have been reported. Some patients have mildly delayed CC development with speech delay and/or autistic features or mildly CC impaired intellectual development. {ECO:0000269|PubMed:26645390, CC ECO:0000269|PubMed:27159988, ECO:0000269|PubMed:27328862, CC ECO:0000269|PubMed:28065826}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. CC Nav1.2/SCN2A subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA46438.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAA46438.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; 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; M94055; AAA18895.1; -; mRNA. DR EMBL; AF059683; AAC14574.1; -; Genomic_DNA. DR EMBL; AF327246; AAG53413.1; -; Genomic_DNA. DR EMBL; AF327226; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327227; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327228; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327229; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327230; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327231; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327232; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327233; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327234; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327235; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327236; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327237; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327238; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327239; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327240; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327241; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327242; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327243; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327244; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327245; AAG53413.1; JOINED; Genomic_DNA. DR EMBL; AF327246; AAG53412.1; -; Genomic_DNA. DR EMBL; AF327226; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327227; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327228; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327229; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327230; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327231; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327232; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327233; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327234; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327235; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327236; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327237; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327238; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327239; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327240; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327241; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327242; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327243; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327244; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AF327245; AAG53412.1; JOINED; Genomic_DNA. DR EMBL; AC011303; AAY14971.1; -; Genomic_DNA. DR EMBL; AC013438; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X65361; CAA46438.1; ALT_SEQ; mRNA. DR EMBL; M91804; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; M55662; AAB65854.2; -; Genomic_DNA. DR CCDS; CCDS33313.1; -. [Q99250-2] DR CCDS; CCDS33314.1; -. [Q99250-1] DR PIR; A46269; A46269. DR PIR; I59194; I59194. DR RefSeq; NP_001035232.1; NM_001040142.1. [Q99250-1] DR RefSeq; NP_001035233.1; NM_001040143.1. [Q99250-2] DR RefSeq; NP_066287.2; NM_021007.2. [Q99250-1] DR RefSeq; XP_005246810.1; XM_005246753.3. DR RefSeq; XP_016860144.1; XM_017004655.1. DR RefSeq; XP_016860145.1; XM_017004656.1. DR RefSeq; XP_016860146.1; XM_017004657.1. DR PDB; 2KAV; NMR; -; A=1777-1882. DR PDB; 4JPZ; X-ray; 3.02 A; B/H=1777-1937. DR PDB; 4RLY; X-ray; 2.50 A; A=1102-1120. DR PDB; 6BUT; NMR; -; B=1901-1927. DR PDB; 6J8E; EM; 3.00 A; A=1-2005. DR PDBsum; 2KAV; -. DR PDBsum; 4JPZ; -. DR PDBsum; 4RLY; -. DR PDBsum; 6BUT; -. DR PDBsum; 6J8E; -. DR AlphaFoldDB; Q99250; -. DR BMRB; Q99250; -. DR EMDB; EMD-9780; -. DR SMR; Q99250; -. DR BioGRID; 112231; 3. DR CORUM; Q99250; -. DR IntAct; Q99250; 7. DR MINT; Q99250; -. DR STRING; 9606.ENSP00000490107; -. DR BindingDB; Q99250; -. DR ChEMBL; CHEMBL4187; -. DR DrugBank; DB13908; Amylmetacresol. 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; DB13961; Fish oil. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB13520; Metergoline. DR DrugBank; DB00776; Oxcarbazepine. DR DrugBank; DB11186; Pentoxyverine. DR DrugBank; DB00252; Phenytoin. 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; DB05232; Tetrodotoxin. DR DrugBank; DB00273; Topiramate. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB00909; Zonisamide. DR DrugCentral; Q99250; -. DR GuidetoPHARMACOLOGY; 579; -. DR TCDB; 1.A.1.10.12; the voltage-gated ion channel (vic) superfamily. DR GlyCosmos; Q99250; 10 sites, No reported glycans. DR GlyGen; Q99250; 10 sites. DR iPTMnet; Q99250; -. DR PhosphoSitePlus; Q99250; -. DR BioMuta; SCN2A; -. DR DMDM; 25014053; -. DR jPOST; Q99250; -. DR MassIVE; Q99250; -. DR PaxDb; 9606-ENSP00000364586; -. DR PeptideAtlas; Q99250; -. DR ProteomicsDB; 78253; -. [Q99250-1] DR ProteomicsDB; 78254; -. [Q99250-2] DR ABCD; Q99250; 1 sequenced antibody. DR Antibodypedia; 33769; 204 antibodies from 24 providers. DR DNASU; 6326; -. DR Ensembl; ENST00000283256.10; ENSP00000283256.6; ENSG00000136531.19. [Q99250-1] DR Ensembl; ENST00000375437.7; ENSP00000364586.2; ENSG00000136531.19. [Q99250-1] DR Ensembl; ENST00000631182.3; ENSP00000486885.1; ENSG00000136531.19. [Q99250-2] DR Ensembl; ENST00000636071.2; ENSP00000490107.1; ENSG00000136531.19. [Q99250-2] DR Ensembl; ENST00000637266.2; ENSP00000490866.1; ENSG00000136531.19. [Q99250-1] DR GeneID; 6326; -. DR KEGG; hsa:6326; -. DR MANE-Select; ENST00000375437.7; ENSP00000364586.2; NM_001040142.2; NP_001035232.1. DR UCSC; uc002udc.4; human. [Q99250-1] DR AGR; HGNC:10588; -. DR CTD; 6326; -. DR DisGeNET; 6326; -. DR GeneCards; SCN2A; -. DR HGNC; HGNC:10588; SCN2A. DR HPA; ENSG00000136531; Tissue enriched (brain). DR MalaCards; SCN2A; -. DR MIM; 182390; gene. DR MIM; 607745; phenotype. DR MIM; 613721; phenotype. DR MIM; 618924; phenotype. DR neXtProt; NX_Q99250; -. DR OpenTargets; ENSG00000136531; -. DR Orphanet; 306; Benign familial infantile epilepsy. DR Orphanet; 140927; Benign familial neonatal-infantile seizures. DR Orphanet; 33069; Dravet syndrome. DR Orphanet; 1934; Early infantile epileptic encephalopathy. DR Orphanet; 36387; Generalized epilepsy with febrile seizures-plus. DR Orphanet; 3451; Infantile spasms syndrome. DR Orphanet; 293181; Malignant migrating focal seizures of infancy. DR PharmGKB; PA35004; -. DR VEuPathDB; HostDB:ENSG00000136531; -. DR eggNOG; KOG2301; Eukaryota. DR GeneTree; ENSGT00940000154224; -. DR HOGENOM; CLU_000540_5_0_1; -. DR InParanoid; Q99250; -. DR OMA; KRTIREC; -. DR PhylomeDB; Q99250; -. DR TreeFam; TF323985; -. DR PathwayCommons; Q99250; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation. DR Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste. DR SignaLink; Q99250; -. DR SIGNOR; Q99250; -. DR BioGRID-ORCS; 6326; 10 hits in 1156 CRISPR screens. DR ChiTaRS; SCN2A; human. DR EvolutionaryTrace; Q99250; -. DR GeneWiki; Nav1.2; -. DR GenomeRNAi; 6326; -. DR Pharos; Q99250; Tclin. DR PRO; PR:Q99250; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q99250; Protein. DR Bgee; ENSG00000136531; Expressed in middle temporal gyrus and 139 other cell types or tissues. DR ExpressionAtlas; Q99250; baseline and differential. DR GO; GO:0030424; C:axon; TAS:BHF-UCL. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL. DR GO; GO:0033270; C:paranode region of axon; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl. DR GO; GO:0030315; C:T-tubule; IEA:Ensembl. DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central. DR GO; GO:0001518; C:voltage-gated sodium channel complex; ISS:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IMP:DisProt. 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:0071456; P:cellular response to hypoxia; ISS:UniProtKB. DR GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0008627; P:intrinsic apoptotic signaling pathway in response to osmotic stress; ISS:UniProtKB. DR GO; GO:0007613; P:memory; ISS:UniProtKB. DR GO; GO:0042552; P:myelination; ISS:BHF-UCL. DR GO; GO:0021675; P:nerve development; IEA:Ensembl. DR GO; GO:0007399; P:nervous system development; ISS:UniProtKB. DR GO; GO:0051402; P:neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0019228; P:neuronal action potential; IMP:UniProtKB. DR GO; GO:0006814; P:sodium ion transport; ISS:UniProtKB. 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; IPR001696; Na_channel_asu. DR InterPro; IPR044564; Na_chnl_inactivation_gate. DR InterPro; IPR010526; Na_trans_assoc_dom. DR InterPro; IPR024583; Na_trans_cytopl. DR InterPro; IPR043203; VGCC_Ca_Na. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR10037:SF278; SODIUM CHANNEL PROTEIN TYPE 2 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 Pfam; PF11933; Na_trans_cytopl; 1. DR PRINTS; PR00170; NACHANNEL. DR SMART; SM00015; IQ; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR PROSITE; PS50096; IQ; 1. DR Genevisible; Q99250; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport; KW Isopeptide bond; Membrane; Phosphoprotein; Reference proteome; Repeat; KW Sodium; Sodium channel; Sodium transport; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation; Voltage-gated channel. FT CHAIN 1..2005 FT /note="Sodium channel protein type 2 subunit alpha" FT /id="PRO_0000048491" FT TOPO_DOM 1..129 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 130..148 FT /note="Helical; Name=S1 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 149..155 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 156..176 FT /note="Helical; Name=S2 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 177..190 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 191..208 FT /note="Helical; Name=S3 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 209..214 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 215..231 FT /note="Helical; Name=S4 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 232..250 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 251..270 FT /note="Helical; Name=S5 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 271..369 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 370..394 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 395..401 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 402..422 FT /note="Helical; Name=S6 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 423..759 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 760..778 FT /note="Helical; Name=S1 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 779..789 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 790..809 FT /note="Helical; Name=S2 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 810..823 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 824..843 FT /note="Helical; Name=S3 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 844..845 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 846..863 FT /note="Helical; Name=S4 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 864..879 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 880..898 FT /note="Helical; Name=S5 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 899..927 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 928..948 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 949..961 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 962..982 FT /note="Helical; Name=S6 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 983..1209 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1210..1227 FT /note="Helical; Name=S1 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1228..1240 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1241..1259 FT /note="Helical; Name=S2 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1260..1273 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1274..1292 FT /note="Helical; Name=S3 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1293..1300 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1301..1319 FT /note="Helical; Name=S4 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1320..1336 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1337..1356 FT /note="Helical; Name=S5 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1357..1408 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 1409..1430 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1431..1447 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1448..1469 FT /note="Helical; Name=S6 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1470..1532 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1533..1550 FT /note="Helical; Name=S1 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1551..1561 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1562..1580 FT /note="Helical; Name=S2 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1581..1592 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1593..1610 FT /note="Helical; Name=S3 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1611..1623 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1624..1640 FT /note="Helical; Name=S4 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1641..1659 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1660..1677 FT /note="Helical; Name=S5 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1678..1699 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 1700..1722 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1723..1752 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1753..1775 FT /note="Helical; Name=S6 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1776..2005 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REPEAT 111..456 FT /note="I" FT /evidence="ECO:0000305" FT REPEAT 741..1013 FT /note="II" FT /evidence="ECO:0000305" FT REPEAT 1190..1504 FT /note="III" FT /evidence="ECO:0000305" FT REPEAT 1513..1811 FT /note="IV" FT /evidence="ECO:0000305" FT DOMAIN 1905..1934 FT /note="IQ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116" FT REGION 28..61 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 494..529 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 590..610 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 917..918 FT /note="Binds SCN2B" FT /evidence="ECO:0000305|PubMed:30765605" FT REGION 1120..1165 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1935..2005 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 28..53 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 510..529 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1935..1959 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1960..1977 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1978..2005 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 330 FT /note="Binds Mu-conotoxin KIIIA" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 362 FT /note="Binds Mu-conotoxin KIIIA" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 909 FT /note="Binds SCN2B; via carbonyl oxygen" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 916 FT /note="Binds Mu-conotoxin KIIIA; via amide nitrogen" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 920 FT /note="Binds Mu-conotoxin KIIIA; via carbonyl oxygen" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 945 FT /note="Binds Mu-conotoxin KIIIA" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 949 FT /note="Binds Mu-conotoxin KIIIA" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 1374 FT /note="Binds Mu-conotoxin KIIIA; via amide nitrogen" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 1429 FT /note="Binds Mu-conotoxin KIIIA" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 1443 FT /note="Binds Mu-conotoxin KIIIA" FT /evidence="ECO:0000305|PubMed:30765605" FT SITE 1489 FT /note="Important for channel closure" FT /evidence="ECO:0000250" FT MOD_RES 4 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 468 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 471 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 484 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 526 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 528 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 531 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 553 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 554 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 558 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 573 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 576 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 589 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 610 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 623 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 687 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 721 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 1506 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 1930 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 1943 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 1963 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 1966 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT MOD_RES 1971 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04775" FT CARBOHYD 212 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 285 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 308 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 340 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT CARBOHYD 1368 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT CARBOHYD 1382 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT CARBOHYD 1393 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT DISULFID 278..338 FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT DISULFID 910 FT /note="Interchain; with SCN2B or SCN4B" FT /evidence="ECO:0000269|PubMed:26894959, FT ECO:0000269|PubMed:30765605, ECO:0007744|PDB:6J8E" FT DISULFID 910 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 912..918 FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT DISULFID 950..959 FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT DISULFID 1366..1386 FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT DISULFID 1731..1746 FT /evidence="ECO:0000269|PubMed:30765605, FT ECO:0007744|PDB:6J8E" FT CROSSLNK 38 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0000250|UniProtKB:P04775" FT VAR_SEQ 209 FT /note="D -> N (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001032" FT VARIANT 12 FT /note="D -> N (found in a patient with autism spectrum FT disorder; likely pathogenic; decreased voltage-gated sodium FT channel activity; faster channel inactivation; loss of FT function)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078448" FT VARIANT 19 FT /note="R -> K (in dbSNP:rs17183814)" FT /evidence="ECO:0000269|PubMed:11371648, FT ECO:0000269|PubMed:12610651, ECO:0000269|PubMed:19786696, FT ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:26555645" FT /id="VAR_029732" FT VARIANT 82 FT /note="D -> G (found in a patient with autism spectrum FT disorder; likely pathogenic; decreased voltage-gated sodium FT channel activity; decreased expression; loss of function)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078449" FT VARIANT 102..2005 FT /note="Missing (found in a patient with intractable FT epilepsy and severe mental decline; likely pathogenic; FT non-conducting; loss of voltage-gated sodium channel FT activity; dominant-negative)" FT /evidence="ECO:0000269|PubMed:15028761" FT /id="VAR_078450" FT VARIANT 132 FT /note="N -> K (in DEE11)" FT /evidence="ECO:0000269|PubMed:24659627" FT /id="VAR_078451" FT VARIANT 136 FT /note="M -> I (in DEE11; responds to ketogenic diet)" FT /evidence="ECO:0000269|PubMed:23708187, FT ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:30415926" FT /id="VAR_078452" FT VARIANT 169..2005 FT /note="Missing (found in a patient with schizofrenia; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:26555645" FT /id="VAR_078453" FT VARIANT 169 FT /note="E -> G (in DEE11)" FT /evidence="ECO:0000269|PubMed:23935176, FT ECO:0000269|PubMed:27864847" FT /id="VAR_069996" FT VARIANT 172 FT /note="I -> V (found in a patient with non-specific acute FT encephalopathy; uncertain significance; FT dbSNP:rs1376337813)" FT /evidence="ECO:0000269|PubMed:26311622" FT /id="VAR_075572" FT VARIANT 188 FT /note="R -> W (in BFIS3; mutant channel inactivates more FT slowly than wild-type whereas the sodium channel FT conductance is not affected; dbSNP:rs121917748)" FT /evidence="ECO:0000269|PubMed:11371648" FT /id="VAR_029733" FT VARIANT 191 FT /note="W -> C (in DEE11; responds to ketogenic diet)" FT /evidence="ECO:0000269|PubMed:29625812" FT /id="VAR_081430" FT VARIANT 191 FT /note="W -> G (found in a patient with drug-resistant focal FT epilepsy; likely pathogenic; dbSNP:rs1057519525)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078195" FT VARIANT 208 FT /note="V -> E (in BFIS3; gain of function mutation; FT hyperpolarizing shift of the activation curve)" FT /evidence="ECO:0000269|PubMed:22612257, FT ECO:0000269|PubMed:30144217" FT /id="VAR_072745" FT VARIANT 211 FT /note="G -> D (in DEE11; the disease progresses to West FT syndrome)" FT /evidence="ECO:0000269|PubMed:23662938" FT /id="VAR_078730" FT VARIANT 212 FT /note="N -> D (in DEE11; the disease progresses to West FT syndrome)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_069997" FT VARIANT 213 FT /note="V -> D (in DEE11)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_069998" FT VARIANT 218 FT /note="T -> K (in DEE11; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26291284" FT /id="VAR_078454" FT VARIANT 220 FT /note="R -> G (in DEE11)" FT /evidence="ECO:0000269|PubMed:25818041" FT /id="VAR_078731" FT VARIANT 223 FT /note="R -> Q (in BFIS3; increased voltage-gated sodium FT channel activity; modified voltage dependence of activation FT and inactivation; gain of function; dbSNP:rs121917752)" FT /evidence="ECO:0000269|PubMed:15048894, FT ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:23360469" FT /id="VAR_029734" FT VARIANT 236 FT /note="T -> S (in DEE11; dbSNP:rs1235044536)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_069999" FT VARIANT 240 FT /note="A -> S (in BFIS3)" FT /evidence="ECO:0000269|PubMed:26291284" FT /id="VAR_078455" FT VARIANT 251 FT /note="V -> I (in DEE11; dbSNP:rs1057519528)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078196" FT VARIANT 252 FT /note="M -> V (in BFIS3; increased voltage-gated sodium FT channel activity; increased persistent sodium current; gain FT of function; dbSNP:rs387906687)" FT /evidence="ECO:0000269|PubMed:20371507" FT /id="VAR_065176" FT VARIANT 261 FT /note="V -> M (in BFIS3; increased voltage-gated sodium FT channel activity; faster recovery from inactivation; gain FT of function; dbSNP:rs1057520413)" FT /evidence="ECO:0000269|PubMed:20371507" FT /id="VAR_065177" FT VARIANT 263 FT /note="A -> T (in DEE11)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070000" FT VARIANT 263 FT /note="A -> V (in DEE11 and EA9; increased voltage-gated FT sodium channel activity; increased persistent sodium FT current; gain of function; dbSNP:rs387906686)" FT /evidence="ECO:0000269|PubMed:20956790, FT ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:26645390, FT ECO:0000269|PubMed:27159988, ECO:0000269|PubMed:27864847, FT ECO:0000269|PubMed:28065826" FT /id="VAR_065178" FT VARIANT 322 FT /note="D -> N (found in a patient with Dravet syndrome; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:19783390, FT ECO:0000269|PubMed:23195492" FT /id="VAR_073428" FT VARIANT 328 FT /note="F -> V (found in a patient with acute encephalopathy FT with biphasic seizures, late reduced diffusion and in a FT patient with Dravet syndrome; uncertain significance; FT dbSNP:rs781204054)" FT /evidence="ECO:0000269|PubMed:16122630, FT ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, FT ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:26311622" FT /id="VAR_064331" FT VARIANT 379 FT /note="R -> H (found in a patient with autism spectrum FT disorder; likely pathogenic; loss of voltage-gated sodium FT channel activity; non-conducting; no dominant-negative FT effect)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078456" FT VARIANT 385 FT /note="F -> Y (in dbSNP:rs2228988)" FT /id="VAR_029735" FT VARIANT 424 FT /note="V -> M (found in a patient with early-onset seizures FT and Rett-like features, including autistic behavior, FT limited hand function with chorea and profound intellectual FT disability; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:28709814" FT /id="VAR_081431" FT VARIANT 430 FT /note="E -> G (in DEE11; dbSNP:rs796053183)" FT /evidence="ECO:0000269|PubMed:24659627" FT /id="VAR_078457" FT VARIANT 430 FT /note="E -> Q (in BFIS3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:17386050" FT /id="VAR_078458" FT VARIANT 467 FT /note="A -> T (found in patients with GEFS+; likely FT pathogenic; dbSNP:rs745774658)" FT /evidence="ECO:0000269|PubMed:29635106" FT /id="VAR_081432" FT VARIANT 524 FT /note="R -> Q (in dbSNP:rs186154973)" FT /evidence="ECO:0000269|PubMed:11371648, FT ECO:0000269|PubMed:19786696" FT /id="VAR_029736" FT VARIANT 575 FT /note="A -> V (there is no significant effects on the FT voltage-dependence of the channel; dbSNP:rs986167267)" FT /evidence="ECO:0000269|PubMed:19786696" FT /id="VAR_065179" FT VARIANT 583..2005 FT /note="Missing (found in a patient with autism spectrum FT disorder; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:25969726" FT /id="VAR_078732" FT VARIANT 649 FT /note="D -> N (found in a patient with Dravet syndrome; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:23195492" FT /id="VAR_078733" FT VARIANT 674 FT /note="T -> K (found in a patient with autism spectrum FT disorder; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:26637798" FT /id="VAR_078734" FT VARIANT 773 FT /note="T -> I (in DEE11; hyperpolarizing shift of the FT activation curve and increased persitent current; gain of FT function)" FT /evidence="ECO:0000269|PubMed:30144217" FT /id="VAR_081433" FT VARIANT 850 FT /note="R -> P (found in a patient with schizofrenia; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:26555645" FT /id="VAR_078459" FT VARIANT 853 FT /note="R -> Q (in DEE11; phenotype consistent with West FT syndrome; decreased neuronal excitability; decreased peak FT sodium current densities; loss of function; FT dbSNP:rs794727152)" FT /evidence="ECO:0000269|PubMed:23935176, FT ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:29844171" FT /id="VAR_070001" FT VARIANT 856 FT /note="R -> L (in DEE11)" FT /evidence="ECO:0000269|PubMed:26291284" FT /id="VAR_078460" FT VARIANT 873 FT /note="I -> M (in DEE11)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078735" FT VARIANT 876 FT /note="N -> T (in DEE11; the disease progresses to West FT syndrome)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070002" FT VARIANT 892 FT /note="V -> I (in BFIS3; dbSNP:rs121917751)" FT /evidence="ECO:0000269|PubMed:15048894" FT /id="VAR_029737" FT VARIANT 896 FT /note="A -> V (in DEE11; dbSNP:rs1057519526)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078197" FT VARIANT 905 FT /note="K -> N (in DEE11; dbSNP:rs796053119)" FT /evidence="ECO:0000269|PubMed:23708187, FT ECO:0000269|PubMed:26291284" FT /id="VAR_078461" FT VARIANT 908 FT /note="K -> E (in BFIS3; increased voltage-gated sodium FT channel activity; gain of function; dbSNP:rs796053122)" FT /evidence="ECO:0000269|PubMed:30144217" FT /id="VAR_081434" FT VARIANT 908 FT /note="K -> R (in dbSNP:rs2228980)" FT /evidence="ECO:0000269|PubMed:26555645" FT /id="VAR_078462" FT VARIANT 928 FT /note="F -> C (in DEE11; mild form with ataxia)" FT /evidence="ECO:0000269|PubMed:23708187, FT ECO:0000269|PubMed:26291284" FT /id="VAR_078463" FT VARIANT 937 FT /note="R -> C (found in a patient with autism spectrum FT disorder; likely pathogenic; loss of voltage-gated sodium FT channel activity; non-conducting; dbSNP:rs796053197)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078464" FT VARIANT 937 FT /note="R -> H (found in a patient with autism spectrum FT disorder; likely pathogenic; loss of voltage-gated sodium FT channel activity; non-conducting; dbSNP:rs1553579488)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078465" FT VARIANT 959..2005 FT /note="Missing (found in a patient with autism spectrum FT disorder; likely pathogenic; loss of voltage-gated sodium FT channel activity; non-conducting)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078466" FT VARIANT 976 FT /note="N -> K (found in a patient with autism; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:26291284" FT /id="VAR_078467" FT VARIANT 987 FT /note="S -> I (in DEE11; dbSNP:rs796053124)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078736" FT VARIANT 999 FT /note="E -> K (in DEE11; the disease progresses to West FT syndrome; dbSNP:rs796053126)" FT /evidence="ECO:0000269|PubMed:23935176, FT ECO:0000269|PubMed:26993267" FT /id="VAR_070003" FT VARIANT 999 FT /note="E -> V (in DEE11)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078737" FT VARIANT 1001 FT /note="N -> K (in BFIS3)" FT /evidence="ECO:0000269|PubMed:16417554, FT ECO:0000269|PubMed:23360469" FT /id="VAR_078468" FT VARIANT 1003 FT /note="L -> I (in BFIS3; dbSNP:rs121917754)" FT /evidence="ECO:0000269|PubMed:15048894" FT /id="VAR_029738" FT VARIANT 1013..2005 FT /note="Missing (found in a patient with autism spectrum FT disorder; likely pathogenic; loss of voltage-gated sodium FT channel activity; non-conducting)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078469" FT VARIANT 1128 FT /note="M -> T (found in a patient with acute encephalitis FT with refractory and repetitive partial seizures; uncertain FT significance; dbSNP:rs373780066)" FT /evidence="ECO:0000269|PubMed:22591750" FT /id="VAR_078470" FT VARIANT 1211 FT /note="E -> K (in DEE11; markedly altered channel FT voltage-dependence; responds to modified Atkins diet; FT dbSNP:rs387906684)" FT /evidence="ECO:0000269|PubMed:19786696, FT ECO:0000269|PubMed:25459969" FT /id="VAR_065180" FT VARIANT 1260 FT /note="K -> E (in DEE11)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078738" FT VARIANT 1260 FT /note="K -> Q (in DEE11)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078739" FT VARIANT 1282 FT /note="V -> F (found in a patient with schizofrenia; FT uncertain significance; dbSNP:rs1184922927)" FT /evidence="ECO:0000269|PubMed:26555645" FT /id="VAR_078471" FT VARIANT 1312 FT /note="R -> T (in DEE11; modified voltage-gated sodium FT channel activity; activated with lowered voltage FT sensitivity; disturbed fast and slow inactivation)" FT /evidence="ECO:0000269|PubMed:19783390, FT ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23195492" FT /id="VAR_073429" FT VARIANT 1316 FT /note="A -> V (in DEE11; dbSNP:rs796053130)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078198" FT VARIANT 1319 FT /note="R -> Q (in BFIS3; modified voltage-gated sodium FT channel activity; modified voltage dependence of activation FT and inactivation; dbSNP:rs121917753)" FT /evidence="ECO:0000269|PubMed:15048894, FT ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:18479388, FT ECO:0000269|PubMed:23360469" FT /id="VAR_029739" FT VARIANT 1321 FT /note="E -> K (in BFIS3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25982755" FT /id="VAR_078740" FT VARIANT 1323 FT /note="M -> V (in DEE11; the disease progresses to West FT syndrome; dbSNP:rs1057519523)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070004" FT VARIANT 1326 FT /note="V -> D (in DEE11; dbSNP:rs796053131)" FT /evidence="ECO:0000269|PubMed:23988467" FT /id="VAR_078472" FT VARIANT 1326 FT /note="V -> L (in DEE11; the disease progresses to West FT syndrome)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070005" FT VARIANT 1330 FT /note="L -> F (in BFIS3; increased voltage-gated sodium FT channel activity; decreased overall channel availability FT during repetitive stimulation; gain of function; no effect FT on kinetics of activation or inactivation; no effect on FT voltage dependence of activation; dbSNP:rs121917749)" FT /evidence="ECO:0000269|PubMed:12243921, FT ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:18479388" FT /id="VAR_029740" FT VARIANT 1336 FT /note="S -> Y (in DEE11; the disease progresses to West FT syndrome)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070006" FT VARIANT 1338 FT /note="M -> T (in DEE11)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070007" FT VARIANT 1342 FT /note="L -> P (in DEE11; dbSNP:rs796053134)" FT /evidence="ECO:0000269|PubMed:24659627, FT ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:26138355" FT /id="VAR_078473" FT VARIANT 1344 FT /note="C -> Y (in DEE11; dbSNP:rs1057519527)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078199" FT VARIANT 1372 FT /note="G -> R (found in a patient with autism spectrum FT disorder; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25969726" FT /id="VAR_078741" FT VARIANT 1386 FT /note="C -> R (found in a patient with autism spectrum FT disorder; likely pathogenic; loss of voltage-gated sodium FT channel activity; non-conducting)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078474" FT VARIANT 1398..2005 FT /note="Missing (in DEE11)" FT /evidence="ECO:0000269|PubMed:23033978" FT /id="VAR_078742" FT VARIANT 1420 FT /note="T -> M (found in a patient with autism spectrum FT disorder; likely pathogenic; decreased voltage-gated sodium FT channel activity; faster channel inactivation; fewer FT channels contribution to macroscopic currents and fewer FT channels expressed on membrane; dbSNP:rs1382026643)" FT /evidence="ECO:0000269|PubMed:28256214" FT /id="VAR_078475" FT VARIANT 1422 FT /note="K -> E (found in a boy with infantile spasms and FT bitemporal glucose hypometabolism; likely pathogenic; FT dbSNP:rs796053137)" FT /evidence="ECO:0000269|PubMed:23827426" FT /id="VAR_070008" FT VARIANT 1435..2005 FT /note="Missing (in DEE11)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078743" FT VARIANT 1460 FT /note="G -> R (found in a patient with non-syndromic FT intellectual disability and epilepsy; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:30062040" FT /id="VAR_081435" FT VARIANT 1473 FT /note="I -> M (in DEE11; increased voltage-gated sodium FT channel activity; markedly altered the voltage-dependence FT of the channel; gain of function; dbSNP:rs387906685)" FT /evidence="ECO:0000269|PubMed:19786696" FT /id="VAR_065181" FT VARIANT 1479 FT /note="Q -> P (in DEE11)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078744" FT VARIANT 1515..2005 FT /note="Missing (found in a patient with autism spectrum FT disorder; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:26637798" FT /id="VAR_078745" FT VARIANT 1522 FT /note="G -> A (in DEE11 and EA9; uncertain significance; no FT effect on voltage-gated sodium channel activity; higher FT current density when associated with G-1882; FT dbSNP:rs147522594)" FT /evidence="ECO:0000269|PubMed:25818041, FT ECO:0000269|PubMed:26645390" FT /id="VAR_078476" FT VARIANT 1531 FT /note="Q -> K (in BFIS3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25982755" FT /id="VAR_078746" FT VARIANT 1548 FT /note="M -> T (in DEE11; dbSNP:rs1057519524)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078200" FT VARIANT 1559 FT /note="M -> V (found in a patient with schizofrenia; FT uncertain significance; dbSNP:rs1163751310)" FT /evidence="ECO:0000269|PubMed:26555645" FT /id="VAR_078477" FT VARIANT 1563 FT /note="L -> V (in BFIS3; increased voltage-gated sodium FT channel activity; impaired fast inactivation; no effect on FT kinetics of activation or inactivation; no effect on FT voltage dependence of activation; gain of function; FT dbSNP:rs121917750)" FT /evidence="ECO:0000269|PubMed:12243921, FT ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:18479388, FT ECO:0000269|PubMed:29844171" FT /id="VAR_029741" FT VARIANT 1589 FT /note="Y -> C (in BFIS3; increased voltage-gated sodium FT channel activity; depolarized shift of steady-state FT inactivation; increased persistent sodium current; slower FT fast inactivation; accelerated recovery of fast FT inactivation; gain of function; dbSNP:rs1553463119)" FT /evidence="ECO:0000269|PubMed:23758435" FT /id="VAR_078478" FT VARIANT 1593 FT /note="G -> R (in DEE11; dbSNP:rs886041259)" FT /evidence="ECO:0000269|PubMed:26291284" FT /id="VAR_078479" FT VARIANT 1596 FT /note="I -> S (in BFIS3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:17386050" FT /id="VAR_078480" FT VARIANT 1623 FT /note="T -> N (in DEE11; the disease progresses to West FT syndrome)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070009" FT VARIANT 1629 FT /note="R -> L (in DEE11)" FT /evidence="ECO:0000269|PubMed:23935176" FT /id="VAR_070010" FT VARIANT 1634 FT /note="G -> D (in EA9; uncertain significance; FT dbSNP:rs796053159)" FT /evidence="ECO:0000269|PubMed:27328862" FT /id="VAR_081436" FT VARIANT 1634 FT /note="G -> V (in DEE11)" FT /evidence="ECO:0000269|PubMed:26291284" FT /id="VAR_078482" FT VARIANT 1641 FT /note="K -> N (in BFIS3; uncertain significance; FT dbSNP:rs767224097)" FT /evidence="ECO:0000269|PubMed:23360469" FT /id="VAR_078747" FT VARIANT 1650 FT /note="L -> P (in DEE11; also found in patients with FT familial episodic ataxia and impairment of speech FT development)" FT /evidence="ECO:0000269|PubMed:26993267, FT ECO:0000269|PubMed:30165711" FT /id="VAR_078748" FT VARIANT 1660 FT /note="L -> W (in DEE11)" FT /evidence="ECO:0000269|PubMed:25457084" FT /id="VAR_078483" FT VARIANT 1744 FT /note="G -> R (found in a patient with autism spectrum FT disorder; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:26637798" FT /id="VAR_078749" FT VARIANT 1823 FT /note="D -> A (found in a patient with schizofrenia; FT uncertain significance; dbSNP:rs138497939)" FT /evidence="ECO:0000269|PubMed:26555645" FT /id="VAR_078484" FT VARIANT 1829 FT /note="L -> F (in DEE11; dbSNP:rs1553463676)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078750" FT VARIANT 1853 FT /note="H -> R (in DEE11)" FT /evidence="ECO:0000269|PubMed:24463883" FT /id="VAR_078751" FT VARIANT 1882 FT /note="R -> G (in EA9; gain of function mutation resulting FT in increased voltage-gated sodium channel activity; FT hyperpolarized activation; higher current density when FT associated with A-1522 compared to wild-type or G-1882 FT alone; dbSNP:rs796053166)" FT /evidence="ECO:0000269|PubMed:26645390" FT /id="VAR_078485" FT VARIANT 1882 FT /note="R -> L (in DEE11; dbSNP:rs794727444)" FT /evidence="ECO:0000269|PubMed:24579881" FT /id="VAR_078486" FT VARIANT 1882 FT /note="R -> Q (in DEE11; increased neuronal excitability; FT increased peak sodium current densities; gain of function; FT dbSNP:rs794727444)" FT /evidence="ECO:0000269|PubMed:23708187, FT ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, FT ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29844171" FT /id="VAR_078201" FT VARIANT 1902 FT /note="R -> T (found in autism; uncertain significance)" FT /evidence="ECO:0000269|PubMed:12610651" FT /id="VAR_029742" FT VARIANT 1918 FT /note="R -> H (in dbSNP:rs201718767)" FT /evidence="ECO:0000269|PubMed:11738931" FT /id="VAR_078487" FT CONFLICT 524 FT /note="R -> L (in Ref. 1; AAA18895)" FT /evidence="ECO:0000305" FT CONFLICT 1325 FT /note="V -> A (in Ref. 1; AAA18895)" FT /evidence="ECO:0000305" FT CONFLICT 1768 FT /note="V -> L (in Ref. 1; AAA18895)" FT /evidence="ECO:0000305" FT CONFLICT 1990 FT /note="K -> R (in Ref. 5; CAA46438)" FT /evidence="ECO:0000305" FT HELIX 118..121 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 124..127 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 129..145 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 156..174 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 190..202 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 204..206 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 207..210 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 218..226 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 227..230 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 234..245 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 246..249 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 251..269 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 273..275 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 276..280 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 317..319 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 323..326 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 329..331 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 361..364 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 367..369 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 370..381 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 386..396 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 399..401 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 402..411 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 412..414 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 415..440 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 742..753 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 754..759 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 760..762 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 763..777 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 785..787 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 788..807 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 810..813 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 823..840 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 847..862 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 865..878 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 879..881 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 882..902 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 904..909 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 914..919 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 928..938 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 939..941 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 944..954 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 956..985 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1114..1116 FT /evidence="ECO:0007829|PDB:4RLY" FT TURN 1192..1194 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1195..1205 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1208..1223 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1224..1227 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1232..1235 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1236..1238 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1239..1264 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1266..1269 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1273..1294 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1302..1305 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1306..1316 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1317..1319 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1321..1330 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1331..1333 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1334..1358 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1360..1363 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1365..1367 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1369..1371 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1377..1379 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1383..1390 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1391..1393 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1397..1399 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1402..1408 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1409..1420 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1424..1432 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1443..1446 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1447..1449 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1450..1459 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1460..1462 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1463..1482 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1492..1496 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1497..1500 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1501..1505 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1520..1528 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1531..1549 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1557..1584 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1593..1615 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1622..1628 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1629..1633 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1636..1641 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1646..1654 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1657..1681 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1682..1685 FT /evidence="ECO:0007829|PDB:6J8E" FT STRAND 1693..1699 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1700..1710 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1711..1715 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1716..1720 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1721..1723 FT /evidence="ECO:0007829|PDB:6J8E" FT TURN 1728..1730 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1749..1784 FT /evidence="ECO:0007829|PDB:6J8E" FT HELIX 1792..1805 FT /evidence="ECO:0007829|PDB:4JPZ" FT STRAND 1811..1814 FT /evidence="ECO:0007829|PDB:4JPZ" FT TURN 1815..1817 FT /evidence="ECO:0007829|PDB:4JPZ" FT HELIX 1818..1823 FT /evidence="ECO:0007829|PDB:4JPZ" FT TURN 1827..1829 FT /evidence="ECO:0007829|PDB:4JPZ" FT HELIX 1836..1839 FT /evidence="ECO:0007829|PDB:4JPZ" FT STRAND 1845..1847 FT /evidence="ECO:0007829|PDB:4JPZ" FT TURN 1848..1850 FT /evidence="ECO:0007829|PDB:4JPZ" FT STRAND 1851..1853 FT /evidence="ECO:0007829|PDB:4JPZ" FT HELIX 1854..1866 FT /evidence="ECO:0007829|PDB:4JPZ" FT HELIX 1870..1886 FT /evidence="ECO:0007829|PDB:4JPZ" FT HELIX 1900..1926 FT /evidence="ECO:0007829|PDB:4JPZ" SQ SEQUENCE 2005 AA; 227975 MW; 8A421AE6C7ED9A37 CRC64; MAQSVLVPPG PDSFRFFTRE SLAAIEQRIA EEKAKRPKQE RKDEDDENGP KPNSDLEAGK SLPFIYGDIP PEMVSVPLED LDPYYINKKT FIVLNKGKAI SRFSATPALY ILTPFNPIRK LAIKILVHSL FNMLIMCTIL TNCVFMTMSN PPDWTKNVEY TFTGIYTFES LIKILARGFC LEDFTFLRDP WNWLDFTVIT FAYVTEFVDL GNVSALRTFR VLRALKTISV IPGLKTIVGA LIQSVKKLSD VMILTVFCLS VFALIGLQLF MGNLRNKCLQ WPPDNSSFEI NITSFFNNSL DGNGTTFNRT VSIFNWDEYI EDKSHFYFLE GQNDALLCGN SSDAGQCPEG YICVKAGRNP NYGYTSFDTF SWAFLSLFRL MTQDFWENLY QLTLRAAGKT YMIFFVLVIF LGSFYLINLI LAVVAMAYEE QNQATLEEAE QKEAEFQQML EQLKKQQEEA QAAAAAASAE SRDFSGAGGI GVFSESSSVA SKLSSKSEKE LKNRRKKKKQ KEQSGEEEKN DRVRKSESED SIRRKGFRFS LEGSRLTYEK RFSSPHQSLL SIRGSLFSPR RNSRASLFSF RGRAKDIGSE NDFADDEHST FEDNDSRRDS LFVPHRHGER RHSNVSQASR ASRVLPILPM NGKMHSAVDC NGVVSLVGGP STLTSAGQLL PEGTTTETEI RKRRSSSYHV SMDLLEDPTS RQRAMSIASI LTNTMEELEE SRQKCPPCWY KFANMCLIWD CCKPWLKVKH LVNLVVMDPF VDLAITICIV LNTLFMAMEH YPMTEQFSSV LSVGNLVFTG IFTAEMFLKI IAMDPYYYFQ EGWNIFDGFI VSLSLMELGL ANVEGLSVLR SFRLLRVFKL AKSWPTLNML IKIIGNSVGA LGNLTLVLAI IVFIFAVVGM QLFGKSYKEC VCKISNDCEL PRWHMHDFFH SFLIVFRVLC GEWIETMWDC MEVAGQTMCL TVFMMVMVIG NLVVLNLFLA LLLSSFSSDN LAATDDDNEM NNLQIAVGRM QKGIDFVKRK IREFIQKAFV RKQKALDEIK PLEDLNNKKD SCISNHTTIE IGKDLNYLKD GNGTTSGIGS SVEKYVVDES DYMSFINNPS LTVTVPIAVG ESDFENLNTE EFSSESDMEE SKEKLNATSS SEGSTVDIGA PAEGEQPEVE PEESLEPEAC FTEDCVRKFK CCQISIEEGK GKLWWNLRKT CYKIVEHNWF ETFIVFMILL SSGALAFEDI YIEQRKTIKT MLEYADKVFT YIFILEMLLK WVAYGFQVYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG AIKSLRTLRA LRPLRALSRF EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCINYT TGEMFDVSVV NNYSECKALI ESNQTARWKN VKVNFDNVGL GYLSLLQVAT FKGWMDIMYA AVDSRNVELQ PKYEDNLYMY LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM TEEQKKYYNA MKKLGSKKPQ KPIPRPANKF QGMVFDFVTK QVFDISIMIL ICLNMVTMMV ETDDQSQEMT NILYWINLVF IVLFTGECVL KLISLRYYYF TIGWNIFDFV VVILSIVGMF LAELIEKYFV SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV MFIYAIFGMS NFAYVKREVG IDDMFNFETF GNSMICLFQI TTSAGWDGLL APILNSGPPD CDPDKDHPGS SVKGDCGNPS VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL SEDDFEMFYE VWEKFDPDAT QFIEFAKLSD FADALDPPLL IAKPNKVQLI AMDLPMVSGD RIHCLDILFA FTKRVLGESG EMDALRIQME ERFMASNPSK VSYEPITTTL KRKQEEVSAI IIQRAYRRYL LKQKVKKVSS IYKKDKGKEC DGTPIKEDTL IDKLNENSTP EKTDMTPSTT SPPSYDSVTK PEKEKFEKDK SEKEDKGKDI RESKK //