SCN2A_HUMAN
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 03-AUG-2022, entry version 218.
DE RecName: Full=Sodium channel protein type 2 subunit alpha;
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; Synonyms=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, AND 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 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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
RP CHARACTERIZATION OF VARIANTS BFIS3 GLN-223; GLN-1319; PHE-1330 AND
RP VAL-1563, AND FUNCTION.
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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, AND FUNCTION.
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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, AND FUNCTION.
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 -!- 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 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}.
CC -!- INTERACTION:
CC Q99250; P62158: CALM3; NbExp=3; IntAct=EBI-724872, EBI-397435;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1325650};
CC Multi-pass membrane protein {ECO:0000269|PubMed:1325650}.
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 ---------------------------------------------------------------------------
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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. [Q99250-1]
DR RefSeq; XP_016860146.1; XM_017004657.1. [Q99250-2]
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 SMR; Q99250; -.
DR BioGRID; 112231; 2.
DR CORUM; Q99250; -.
DR IntAct; Q99250; 8.
DR MINT; Q99250; -.
DR STRING; 9606.ENSP00000364586; -.
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; 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 GlyGen; Q99250; 10 sites.
DR iPTMnet; Q99250; -.
DR PhosphoSitePlus; Q99250; -.
DR BioMuta; SCN2A; -.
DR DMDM; 25014053; -.
DR jPOST; Q99250; -.
DR MassIVE; Q99250; -.
DR PaxDb; Q99250; -.
DR PeptideAtlas; Q99250; -.
DR PRIDE; Q99250; -.
DR ProteomicsDB; 78253; -. [Q99250-1]
DR ProteomicsDB; 78254; -. [Q99250-2]
DR ABCD; Q99250; 1 sequenced antibody.
DR Antibodypedia; 33769; 175 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 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; CCENWLT; -.
DR OrthoDB; 56920at2759; -.
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 1068 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 138 other tissues.
DR ExpressionAtlas; Q99250; baseline and differential.
DR Genevisible; Q99250; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0034706; C:sodium channel complex; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IEA:Ensembl.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IBA:GO_Central.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IMP:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0008627; P:intrinsic apoptotic signaling pathway in response to osmotic stress; ISS:UniProtKB.
DR GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:0042552; P:myelination; ISS:BHF-UCL.
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; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; ISS:UniProtKB.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 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.
DR InterPro; IPR024583; Na_trans_cytopl.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 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 PROSITE; PS50096; IQ; 1.
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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder; decreased voltage-
FT gated sodium channel activity; faster channel inactivation;
FT loss of 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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder; decreased voltage-
FT gated sodium channel activity; decreased expression; loss
FT of function)"
FT /evidence="ECO:0000269|PubMed:28256214"
FT /id="VAR_078449"
FT VARIANT 102..2005
FT /note="Missing (probable disease-associated variant found
FT in a patient with intractable epilepsy and severe mental
FT decline; non-conducting; loss of voltage-gated sodium
FT channel 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 unknown pathological 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; unknown pathological 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 (probable disease-associated variant found in
FT a patient with drug-resistant focal epilepsy;
FT 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; unknown pathological
FT 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 unknown pathological 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; unknown pathological
FT significance; 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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder; loss of voltage-
FT gated sodium channel activity; non-conducting; no dominant-
FT negative 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 (probable disease-associated variant found in
FT a patient with early-onset seizures and Rett-like features,
FT including autistic behavior, limited hand function with
FT chorea and profound intellectual disability)"
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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:17386050"
FT /id="VAR_078458"
FT VARIANT 467
FT /note="A -> T (probable disease-associated variant found in
FT patients with GEFS+; 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 (probable disease-associated variant found
FT in a patient with autism spectrum disorder)"
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 unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23195492"
FT /id="VAR_078733"
FT VARIANT 674
FT /note="T -> K (probable disease-associated variant found in
FT a patient with autism spectrum disorder)"
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 unknown pathological 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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder; loss of voltage-
FT gated sodium channel activity; non-conducting;
FT dbSNP:rs796053197)"
FT /evidence="ECO:0000269|PubMed:28256214"
FT /id="VAR_078464"
FT VARIANT 937
FT /note="R -> H (probable disease-associated variant found in
FT a patient with autism spectrum disorder; loss of voltage-
FT gated sodium channel activity; non-conducting;
FT dbSNP:rs1553579488)"
FT /evidence="ECO:0000269|PubMed:28256214"
FT /id="VAR_078465"
FT VARIANT 959..2005
FT /note="Missing (probable disease-associated variant found
FT in a patient with autism spectrum disorder; loss of
FT voltage-gated sodium 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; unknown
FT pathological 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 (probable disease-associated variant found
FT in a patient with autism spectrum disorder; loss of
FT voltage-gated sodium 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; unknown
FT pathological 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 voltage-
FT 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 unknown pathological 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; unknown pathological
FT 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; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25969726"
FT /id="VAR_078741"
FT VARIANT 1386
FT /note="C -> R (probable disease-associated variant found in
FT a patient with autism spectrum disorder; loss of voltage-
FT gated sodium 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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder; decreased voltage-
FT gated sodium channel activity; faster channel inactivation;
FT fewer channels contribution to macroscopic currents and
FT fewer channels expressed on membrane; dbSNP:rs1382026643)"
FT /evidence="ECO:0000269|PubMed:28256214"
FT /id="VAR_078475"
FT VARIANT 1422
FT /note="K -> E (probable disease-associated variant found in
FT a boy with infantile spasms and bitemporal glucose
FT hypometabolism; 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 (probable disease-associated variant found in
FT a patient with non-syndromic intellectual disability and
FT epilepsy)"
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 (probable disease-associated variant found
FT in a patient with autism spectrum disorder)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078745"
FT VARIANT 1522
FT /note="G -> A (in DEE11 and EA9; unknown pathological
FT significance; no effect on voltage-gated sodium channel
FT activity; higher current density when associated with G-
FT 1882; 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; unknown pathological
FT 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 unknown pathological 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; unknown pathological
FT 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; unknown pathological 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; unknown pathological 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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078749"
FT VARIANT 1823
FT /note="D -> A (found in a patient with schizofrenia;
FT unknown pathological 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; unknown pathological
FT 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
