GenomeNet

Database: UniProt
Entry: SCN9A_HUMAN
LinkDB: SCN9A_HUMAN
Original site: SCN9A_HUMAN 
ID   SCN9A_HUMAN             Reviewed;        1988 AA.
AC   Q15858; A1BUH5; Q6B4R9; Q6B4S0; Q6B4S1; Q70HX1; Q70HX2; Q8WTU1;
AC   Q8WWN4;
DT   23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 3.
DT   27-SEP-2017, entry version 164.
DE   RecName: Full=Sodium channel protein type 9 subunit alpha {ECO:0000305};
DE   AltName: Full=Neuroendocrine sodium channel {ECO:0000303|PubMed:7720699};
DE            Short=hNE-Na {ECO:0000303|PubMed:7720699};
DE   AltName: Full=Peripheral sodium channel 1;
DE            Short=PN1 {ECO:0000250|UniProtKB:O08562};
DE   AltName: Full=Sodium channel protein type IX subunit alpha;
DE   AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.7;
GN   Name=SCN9A {ECO:0000312|HGNC:HGNC:10597}; Synonyms=NENA;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION IN VOLTAGE-EVOKED
RP   DEPOLARIZATION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY, AND
RP   VARIANT ARG-1161.
RC   TISSUE=Thyroid;
RX   PubMed=7720699;
RA   Klugbauer N., Lacinova L., Flockerzi V., Hofmann F.;
RT   "Structure and functional expression of a new member of the
RT   tetrodotoxin-sensitive voltage-activated sodium channel family from
RT   human neuroendocrine cells.";
RL   EMBO J. 14:1084-1090(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INVOLVEMENT IN CONGENITAL
RP   INSENSITIVITY TO PAIN, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP   VARIANT ARG-1161.
RX   PubMed=17167479; DOI=10.1038/nature05413;
RA   Cox J.J., Reimann F., Nicholas A.K., Thornton G., Roberts E.,
RA   Springell K., Karbani G., Jafri H., Mannan J., Raashid Y.,
RA   Al-Gazali L., Hamamy H., Valente E.M., Gorman S., Williams R.,
RA   McHale D.P., Wood J.N., Gribble F.M., Woods C.G.;
RT   "An SCN9A channelopathy causes congenital inability to experience
RT   pain.";
RL   Nature 444:894-898(2006).
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.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 136-674 (ISOFORMS 1; 2; 3 AND 4), AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Spinal ganglion;
RX   PubMed=15302875; DOI=10.1074/jbc.M406387200;
RA   Raymond C.K., Castle J.C., Garrett-Engele P.W., Armour C.D., Kan Z.G.,
RA   Tsinoremas N.T., Johnson J.M.;
RT   "Expression of alternatively spliced sodium channel alpha-subunit
RT   genes: unique splicing patterns are observed in dorsal root ganglia.";
RL   J. Biol. Chem. 279:46234-46241(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 150-264 AND 1340-1400.
RA   Diss J.K.J., Fraser S.P., Coombes R.C., Djamgoz M.B.A.;
RT   "Upregulation of voltage-gated Na+ channel expression and metastatic
RT   potential in human breast cancer: correlative studies on cell lines
RT   and biopsy tissues.";
RL   Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 840-958, AND VARIANTS PERYTHM
RP   THR-859 AND HIS-869.
RX   PubMed=14985375; DOI=10.1136/jmg.2003.012153;
RA   Yang Y., Wang Y., Li S., Xu Z., Li H., Ma L., Fan J., Bu D., Liu B.,
RA   Fan Z., Wu G., Jin J., Ding B., Zhu X., Shen Y.;
RT   "Mutations in SCN9A, encoding a sodium channel alpha subunit, in
RT   patients with primary erythermalgia.";
RL   J. Med. Genet. 41:171-174(2004).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=9169448; DOI=10.1074/jbc.272.23.14805;
RA   Sangameswaran L., Fish L.M., Koch B.D., Rabert D.K., Delgado S.G.,
RA   Ilnicka M., Jakeman L.B., Novakovic S., Wong K., Sze P., Tzoumaka E.,
RA   Stewart G.R., Herman R.C., Chan H., Eglen R.M., Hunter J.C.;
RT   "A novel tetrodotoxin-sensitive, voltage-gated sodium channel
RT   expressed in rat and human dorsal root ganglia.";
RL   J. Biol. Chem. 272:14805-14809(1997).
RN   [8]
RP   FUNCTION IN VOLTAGE-EVOKED DEPOLARIZATION, AND TISSUE SPECIFICITY.
RX   PubMed=15178348; DOI=10.1016/j.febslet.2004.04.092;
RA   Jo T., Nagata T., Iida H., Imuta H., Iwasawa K., Ma J., Hara K.,
RA   Omata M., Nagai R., Takizawa H., Nagase T., Nakajima T.;
RT   "Voltage-gated sodium channel expressed in cultured human smooth
RT   muscle cells: involvement of SCN9A.";
RL   FEBS Lett. 567:339-343(2004).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, PHOSPHORYLATION AT SER-1490,
RP   AND MUTAGENESIS OF SER-1490.
RX   PubMed=25240195; DOI=10.1016/j.febslet.2014.09.011;
RA   Tan Z.Y., Priest B.T., Krajewski J.L., Knopp K.L., Nisenbaum E.S.,
RA   Cummins T.R.;
RT   "Protein kinase C enhances human sodium channel hNav1.7 resurgent
RT   currents via a serine residue in the domain III-IV linker.";
RL   FEBS Lett. 588:3964-3969(2014).
RN   [10]
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.,
RA   Wickenden A.D., Olivera B.M., Yoshikami D., Zhang M.M.;
RT   "A disulfide tether stabilizes the block of sodium channels by the
RT   conotoxin muO[section sign]-GVIIJ.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:2758-2763(2014).
RN   [11]
RP   SUBUNIT, AND INTERACTION WITH THE SPIDER
RP   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.,
RA   Bosmans F., Adams D.J., Lewis R.J., Alewood P.F., Mobli M.,
RA   Christie M.J., Rash L.D.;
RT   "The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance
RT   of the S1-S2 voltage-sensor region for sodium channel subtype
RT   selectivity.";
RL   Sci. Rep. 7:974-988(2017).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (3.53 ANGSTROMS) OF 1527-1559 AND 1581-1622,
RP   FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RX   PubMed=26680203; DOI=10.1126/science.aac5464;
RA   Ahuja S., Mukund S., Deng L., Khakh K., Chang E., Ho H., Shriver S.,
RA   Young C., Lin S., Johnson J.P. Jr., Wu P., Li J., Coons M., Tam C.,
RA   Brillantes B., Sampang H., Mortara K., Bowman K.K., Clark K.R.,
RA   Estevez A., Xie Z., Verschoof H., Grimwood M., Dehnhardt C.,
RA   Andrez J.C., Focken T., Sutherlin D.P., Safina B.S., Starovasnik M.A.,
RA   Ortwine D.F., Franke Y., Cohen C.J., Hackos D.H., Koth C.M.,
RA   Payandeh J.;
RT   "Structural basis of Nav1.7 inhibition by an isoform-selective small-
RT   molecule antagonist.";
RL   Science 350:0-0(2015).
RN   [13]
RP   CHARACTERIZATION OF VARIANTS PERYTHM THR-859 AND HIS-869, FUNCTION,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=15385606; DOI=10.1523/JNEUROSCI.2695-04.2004;
RA   Cummins T.R., Dib-Hajj S.D., Waxman S.G.;
RT   "Electrophysiological properties of mutant Nav1.7 sodium channels in a
RT   painful inherited neuropathy.";
RL   J. Neurosci. 24:8232-8236(2004).
RN   [14]
RP   VARIANT PERYTHM THR-241.
RX   PubMed=16216943; DOI=10.1001/archneur.62.10.1587;
RA   Michiels J.J., te Morsche R.H.M., Jansen J.B.M.J., Drenth J.P.H.;
RT   "Autosomal dominant erythermalgia associated with a novel mutation in
RT   the voltage-gated sodium channel alpha subunit Nav1.7.";
RL   Arch. Neurol. 62:1587-1590(2005).
RN   [15]
RP   VARIANT PERYTHM VAL-1460, AND CHARACTERIZATION OF VARIANT PERYTHM
RP   VAL-1460.
RX   PubMed=15958509; DOI=10.1093/brain/awh514;
RA   Dib-Hajj S.D., Rush A.M., Cummins T.R., Hisama F.M., Novella S.,
RA   Tyrrell L., Marshall L., Waxman S.G.;
RT   "Gain-of-function mutation in Nav1.7 in familial erythromelalgia
RT   induces bursting of sensory neurons.";
RL   Brain 128:1847-1854(2005).
RN   [16]
RP   VARIANTS PERYTHM SER-216; LYS-395; THR-859 AND PHE-869, AND VARIANT
RP   ARG-1161.
RX   PubMed=15955112; DOI=10.1111/j.0022-202X.2005.23737.x;
RA   Drenth J.P., te Morsche R.H., Guillet G., Taieb A., Kirby R.L.,
RA   Jansen J.B.;
RT   "SCN9A mutations define primary erythermalgia as a neuropathic
RT   disorder of voltage gated sodium channels.";
RL   J. Invest. Dermatol. 124:1333-1338(2005).
RN   [17]
RP   VARIANT PERYTHM PHE-869, AND CHARACTERIZATION OF VARIANT PERYTHM
RP   PHE-869.
RX   PubMed=16392115; DOI=10.1002/ana.20776;
RA   Han C., Rush A.M., Dib-Hajj S.D., Li S., Xu Z., Wang Y., Tyrrell L.,
RA   Wang X., Yang Y., Waxman S.G.;
RT   "Sporadic onset of erythermalgia: a gain-of-function mutation in
RT   Nav1.7.";
RL   Ann. Neurol. 59:553-558(2006).
RN   [18]
RP   CHARACTERIZATION OF VARIANT PERYTHM SER-216, FUNCTION, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=16988069; DOI=10.1212/01.wnl.0000231514.33603.1e;
RA   Choi J.S., Dib-Hajj S.D., Waxman S.G.;
RT   "Inherited erythermalgia: limb pain from an S4 charge-neutral Na
RT   channelopathy.";
RL   Neurology 67:1563-1567(2006).
RN   [19]
RP   VARIANTS PEPD CYS-1007; PHE-1309; ASP-1309; PHE-1310; THR-1472;
RP   VAL-1473; ILE-1475 AND LYS-1638, CHARACTERIZATION OF VARIANTS PEPD
RP   THR-1472; ILE-1475 AND LYS-1638, AND FUNCTION.
RX   PubMed=17145499; DOI=10.1016/j.neuron.2006.10.006;
RA   Fertleman C.R., Baker M.D., Parker K.A., Moffatt S., Elmslie F.V.,
RA   Abrahamsen B., Ostman J., Klugbauer N., Wood J.N., Gardiner R.M.,
RA   Rees M.;
RT   "SCN9A mutations in paroxysmal extreme pain disorder: allelic variants
RT   underlie distinct channel defects and phenotypes.";
RL   Neuron 52:767-774(2006).
RN   [20]
RP   CHARACTERIZATION OF VARIANT PERYTHM HIS-869.
RX   PubMed=16702558; DOI=10.1073/pnas.0602813103;
RA   Rush A.M., Dib-Hajj S.D., Liu S., Cummins T.R., Black J.A.,
RA   Waxman S.G.;
RT   "A single sodium channel mutation produces hyper- or hypoexcitability
RT   in different types of neurons.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:8245-8250(2006).
RN   [21]
RP   VARIANT PERYTHM GLU-1643, CHARACTERIZATION OF VARIANT PERYTHM
RP   GLU-1643, VARIANT PEPD GLU-1643, AND CHARACTERIZATION OF VARIANT PEPD
RP   GLU-1643.
RX   PubMed=18945915; DOI=10.1523/JNEUROSCI.3443-08.2008;
RA   Estacion M., Dib-Hajj S.D., Benke P.J., Te Morsche R.H., Eastman E.M.,
RA   Macala L.J., Drenth J.P., Waxman S.G.;
RT   "NaV1.7 gain-of-function mutations as a continuum: A1632E displays
RT   physiological changes associated with erythromelalgia and paroxysmal
RT   extreme pain disorder mutations and produces symptoms of both
RT   disorders.";
RL   J. Neurosci. 28:11079-11088(2008).
RN   [22]
RP   VARIANT PERYTHM ARG-10, CHARACTERIZATION OF VARIANTS PERYTHM ARG-10
RP   AND THR-859, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=19369487; DOI=10.1093/brain/awp078;
RA   Han C., Dib-Hajj S.D., Lin Z., Li Y., Eastman E.M., Tyrrell L.,
RA   Cao X., Yang Y., Waxman S.G.;
RT   "Early- and late-onset inherited erythromelalgia: genotype-phenotype
RT   correlation.";
RL   Brain 132:1711-1722(2009).
RN   [23]
RP   VARIANTS GEFS+7 TYR-641 AND ARG-666, VARIANTS FEB3B VAL-62 AND
RP   GLN-149, AND VARIANTS MET-228; ASN-490; LYS-519; MET-695; TYR-710;
RP   VAL-750; PHE-1134; GLN-1171 AND VAL-1278.
RX   PubMed=19763161; DOI=10.1371/journal.pgen.1000649;
RA   Singh N.A., Pappas C., Dahle E.J., Claes L.R., Pruess T.H.,
RA   De Jonghe P., Thompson J., Dixon M., Gurnett C., Peiffer A.,
RA   White H.S., Filloux F., Leppert M.F.;
RT   "A role of SCN9A in human epilepsies, as a cause of febrile seizures
RT   and as a potential modifier of Dravet syndrome.";
RL   PLoS Genet. 5:E1000649-E1000649(2009).
RN   [24]
RP   VARIANTS CIP GLN-907 AND 1381-ARG--LEU-1385 DEL, AND CHARACTERIZATION
RP   OF VARIANTS CIP GLN-907 AND 1381-ARG--LEU-1385 DEL.
RX   PubMed=20635406; DOI=10.1002/humu.21325;
RA   Cox J.J., Sheynin J., Shorer Z., Reimann F., Nicholas A.K.,
RA   Zubovic L., Baralle M., Wraige E., Manor E., Levy J., Woods C.G.,
RA   Parvari R.;
RT   "Congenital insensitivity to pain: novel SCN9A missense and in-frame
RT   deletion mutations.";
RL   Hum. Mutat. 31:E1670-E1686(2010).
RN   [25]
RP   VARIANT PEPD PRO-1623, AND CHARACTERIZATION OF VARIANT PEPD PRO-1623.
RX   PubMed=25285947; DOI=10.1097/ALN.0000000000000476;
RA   Suter M.R., Bhuiyan Z.A., Laedermann C.J., Kuntzer T., Schaller M.,
RA   Stauffacher M.W., Roulet E., Abriel H., Decosterd I., Wider C.;
RT   "p.L1612P, a novel voltage-gated sodium channel Nav1.7 mutation
RT   inducing a cold sensitive paroxysmal extreme pain disorder.";
RL   Anesthesiology 122:414-423(2015).
RN   [26]
RP   VARIANT PERYTHM THR-1643, CHARACTERIZATION OF VARIANT PERYTHM
RP   THR-1643, MUTAGENESIS OF ALA-1643, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=24311784; DOI=10.1074/jbc.M113.502211;
RA   Eberhardt M., Nakajima J., Klinger A.B., Neacsu C., Huhne K.,
RA   O'Reilly A.O., Kist A.M., Lampe A.K., Fischer K., Gibson J., Nau C.,
RA   Winterpacht A., Lampert A.;
RT   "Inherited pain: sodium channel Nav1.7 A1632T mutation causes
RT   erythromelalgia due to a shift of fast inactivation.";
RL   J. Biol. Chem. 289:1971-1980(2014).
CC   -!- FUNCTION: Mediates the voltage-dependent sodium ion permeability
CC       of excitable membranes. Assuming opened or closed conformations in
CC       response to the voltage difference across the membrane, the
CC       protein forms a sodium-selective channel through which Na(+) ions
CC       may pass in accordance with their electrochemical gradient
CC       (PubMed:7720699, PubMed:17167479, PubMed:25240195,
CC       PubMed:26680203, PubMed:15385606, PubMed:16988069,
CC       PubMed:17145499, PubMed:19369487, PubMed:24311784). It is a
CC       tetrodotoxin-sensitive Na(+) channel isoform (PubMed:7720699).
CC       Plays a role in pain mechanisms, especially in the development of
CC       inflammatory pain (PubMed:17167479, PubMed:17145499,
CC       PubMed:19369487, PubMed:24311784). {ECO:0000269|PubMed:15178348,
CC       ECO:0000269|PubMed:15385606, ECO:0000269|PubMed:16988069,
CC       ECO:0000269|PubMed:17145499, ECO:0000269|PubMed:17167479,
CC       ECO:0000269|PubMed:19369487, ECO:0000269|PubMed:24311784,
CC       ECO:0000269|PubMed:25240195, ECO:0000269|PubMed:26680203,
CC       ECO:0000269|PubMed:7720699}.
CC   -!- SUBUNIT: The sodium channel complex consists of a large, channel-
CC       forming alpha subunit and 2-3 smaller, ancillary beta subunits
CC       (PubMed:7720699, PubMed:17167479, PubMed:25240195). Interacts with
CC       NEDD4 and NEDD4L (By similarity). Interacts with the conotoxin
CC       GVIIJ (PubMed:24497506). Interacts with the conotoxin GVIIJ
CC       (PubMed:24497506). Interacts with the spider beta/delta-
CC       theraphotoxin-Pre1a (PubMed:28428547).
CC       {ECO:0000250|UniProtKB:Q62205, ECO:0000269|PubMed:17167479,
CC       ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:25240195,
CC       ECO:0000269|PubMed:28428547, ECO:0000269|PubMed:7720699}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15385606,
CC       ECO:0000269|PubMed:17167479, ECO:0000269|PubMed:19369487,
CC       ECO:0000269|PubMed:24311784, ECO:0000269|PubMed:25240195,
CC       ECO:0000269|PubMed:26680203, ECO:0000269|PubMed:7720699}; Multi-
CC       pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Cell
CC       projection {ECO:0000250|UniProtKB:O08562}. Note=In neurite
CC       terminals. {ECO:0000250|UniProtKB:O08562}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q15858-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q15858-2; Sequence=VSP_012028;
CC       Name=3;
CC         IsoId=Q15858-3; Sequence=VSP_012029;
CC       Name=4;
CC         IsoId=Q15858-4; Sequence=VSP_012028, VSP_012029;
CC   -!- TISSUE SPECIFICITY: Expressed strongly in dorsal root ganglion,
CC       with only minor levels elsewhere in the body, smooth muscle cells,
CC       MTC cell line and C-cell carcinoma. Isoform 1 is expressed
CC       preferentially in the central and peripheral nervous system.
CC       Isoform 2 is expressed preferentially in the dorsal root ganglion.
CC       {ECO:0000269|PubMed:15178348, ECO:0000269|PubMed:15302875,
CC       ECO:0000269|PubMed:7720699, ECO:0000269|PubMed:9169448}.
CC   -!- DOMAIN: The sequence contains 4 internal repeats, each with 5
CC       hydrophobic segments (S1, S2, S3, S5, S6) and one positively
CC       charged segment (S4). Segments S4 are probably the voltage-sensors
CC       and are characterized by a series of positively charged amino
CC       acids at every third position. {ECO:0000305}.
CC   -!- PTM: Phosphorylation at Ser-1490 by PKC in a highly conserved
CC       cytoplasmic loop increases peak sodium currents.
CC       {ECO:0000269|PubMed:25240195}.
CC   -!- PTM: Ubiquitinated by NEDD4L; which may promote its endocytosis.
CC       Does not seem to be ubiquitinated by NEDD4.
CC       {ECO:0000250|UniProtKB:Q62205}.
CC   -!- DISEASE: Primary erythermalgia (PERYTHM) [MIM:133020]: Autosomal
CC       dominant disease characterized by recurrent episodes of severe
CC       pain associated with redness and warmth in the feet or hands.
CC       {ECO:0000269|PubMed:14985375, ECO:0000269|PubMed:15385606,
CC       ECO:0000269|PubMed:15955112, ECO:0000269|PubMed:15958509,
CC       ECO:0000269|PubMed:16216943, ECO:0000269|PubMed:16392115,
CC       ECO:0000269|PubMed:16702558, ECO:0000269|PubMed:16988069,
CC       ECO:0000269|PubMed:18945915, ECO:0000269|PubMed:19369487,
CC       ECO:0000269|PubMed:24311784}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Indifference to pain, congenital, autosomal recessive
CC       (CIP) [MIM:243000]: A disorder characterized by congenital
CC       inability to perceive any form of pain, in any part of the body.
CC       All other sensory modalities are preserved and the peripheral and
CC       central nervous systems are apparently intact. Patients perceive
CC       the sensations of touch, warm and cold temperature,
CC       proprioception, tickle and pressure, but not painful stimuli.
CC       There is no evidence of a motor or sensory neuropathy, either
CC       axonal or demyelinating. {ECO:0000269|PubMed:20635406}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Paroxysmal extreme pain disorder (PEPD) [MIM:167400]:
CC       Autosomal dominant paroxysmal disorder of pain and autonomic
CC       dysfunction. The distinctive features are paroxysmal episodes of
CC       burning pain in the rectal, ocular, and mandibular areas
CC       accompanied by autonomic manifestations such as skin flushing.
CC       {ECO:0000269|PubMed:17145499, ECO:0000269|PubMed:18945915,
CC       ECO:0000269|PubMed:25285947}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Generalized epilepsy with febrile seizures plus 7
CC       (GEFS+7) [MIM:613863]: A rare autosomal dominant, familial
CC       condition with incomplete penetrance and large intrafamilial
CC       variability. Patients display febrile seizures persisting
CC       sometimes beyond the age of 6 years and/or a variety of afebrile
CC       seizure types. This disease combines febrile seizures, generalized
CC       seizures often precipitated by fever at age 6 years or more, and
CC       partial seizures, with a variable degree of severity.
CC       {ECO:0000269|PubMed:19763161}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Febrile seizures, familial, 3B (FEB3B) [MIM:613863]:
CC       Seizures associated with febrile episodes in childhood without any
CC       evidence of intracranial infection or defined pathologic or
CC       traumatic cause. It is a common condition, affecting 2-5% of
CC       children aged 3 months to 5 years. The majority are simple febrile
CC       seizures (generally defined as generalized onset, single seizures
CC       with a duration of less than 30 minutes). Complex febrile seizures
CC       are characterized by focal onset, duration greater than 30
CC       minutes, and/or more than one seizure in a 24 hour period. The
CC       likelihood of developing epilepsy following simple febrile
CC       seizures is low. Complex febrile seizures are associated with a
CC       moderately increased incidence of epilepsy.
CC       {ECO:0000269|PubMed:19763161}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC       Nav1.7/SCN9A subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=SCN9A entry;
CC       URL="https://en.wikipedia.org/wiki/SCN9A";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Silent pain - Issue 102
CC       of February 2009;
CC       URL="http://web.expasy.org/spotlight/back_issues/102";
DR   EMBL; X82835; CAA58042.1; -; mRNA.
DR   EMBL; DQ857292; ABI51981.1; -; mRNA.
DR   EMBL; AC074101; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC107082; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC108146; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AY682084; AAT85833.1; -; mRNA.
DR   EMBL; AY682085; AAT85834.1; -; mRNA.
DR   EMBL; AY682086; AAT85835.1; -; mRNA.
DR   EMBL; AJ310882; CAC84550.1; -; mRNA.
DR   EMBL; AJ310883; CAC84551.1; -; mRNA.
DR   EMBL; AJ310897; CAC84537.1; -; mRNA.
DR   EMBL; AJ580918; CAE45644.1; -; Genomic_DNA.
DR   EMBL; AJ580919; CAE45645.1; -; Genomic_DNA.
DR   CCDS; CCDS46441.1; -. [Q15858-3]
DR   PIR; S54771; S54771.
DR   RefSeq; NP_002968.1; NM_002977.3.
DR   RefSeq; XP_005246814.1; XM_005246757.2. [Q15858-1]
DR   RefSeq; XP_011509918.1; XM_011511616.2. [Q15858-1]
DR   RefSeq; XP_011509919.1; XM_011511617.2. [Q15858-2]
DR   RefSeq; XP_011509920.1; XM_011511618.2. [Q15858-4]
DR   UniGene; Hs.439145; -.
DR   PDB; 5EK0; X-ray; 3.53 A; A/B/C/D=1527-1559, A/B/C/D=1581-1622.
DR   PDBsum; 5EK0; -.
DR   ProteinModelPortal; Q15858; -.
DR   IntAct; Q15858; 2.
DR   STRING; 9606.ENSP00000386306; -.
DR   BindingDB; Q15858; -.
DR   ChEMBL; CHEMBL4296; -.
DR   DrugBank; DB06218; Lacosamide.
DR   DrugBank; DB00281; Lidocaine.
DR   DrugBank; DB00243; Ranolazine.
DR   DrugBank; DB06201; Rufinamide.
DR   DrugBank; DB00313; Valproic Acid.
DR   DrugBank; DB00909; Zonisamide.
DR   GuidetoPHARMACOLOGY; 584; -.
DR   TCDB; 1.A.1.10.5; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; Q15858; -.
DR   PhosphoSitePlus; Q15858; -.
DR   BioMuta; SCN9A; -.
DR   DMDM; 327478559; -.
DR   EPD; Q15858; -.
DR   PaxDb; Q15858; -.
DR   PeptideAtlas; Q15858; -.
DR   PRIDE; Q15858; -.
DR   Ensembl; ENST00000303354; ENSP00000304748; ENSG00000169432. [Q15858-1]
DR   Ensembl; ENST00000409435; ENSP00000386330; ENSG00000169432. [Q15858-1]
DR   Ensembl; ENST00000409672; ENSP00000386306; ENSG00000169432. [Q15858-3]
DR   GeneID; 6335; -.
DR   KEGG; hsa:6335; -.
DR   UCSC; uc002udr.2; human. [Q15858-1]
DR   CTD; 6335; -.
DR   DisGeNET; 6335; -.
DR   EuPathDB; HostDB:ENSG00000169432.14; -.
DR   GeneCards; SCN9A; -.
DR   GeneReviews; SCN9A; -.
DR   HGNC; HGNC:10597; SCN9A.
DR   HPA; CAB013679; -.
DR   HPA; HPA061843; -.
DR   MalaCards; SCN9A; -.
DR   MIM; 133020; phenotype.
DR   MIM; 167400; phenotype.
DR   MIM; 243000; phenotype.
DR   MIM; 603415; gene.
DR   MIM; 613863; phenotype.
DR   neXtProt; NX_Q15858; -.
DR   OpenTargets; ENSG00000169432; -.
DR   Orphanet; 88642; Channelopathy-associated congenital insensitivity to pain.
DR   Orphanet; 33069; Dravet syndrome.
DR   Orphanet; 1956; Erythromelalgia.
DR   Orphanet; 36387; Generalized epilepsy with febrile seizures-plus.
DR   Orphanet; 970; Hereditary sensory and autonomic neuropathy type 2.
DR   Orphanet; 46348; Paroxysmal extreme pain disorder.
DR   Orphanet; 90026; Primary erythermalgia.
DR   Orphanet; 306577; Sodium channelopathy-related small fiber neuropathy.
DR   PharmGKB; PA35010; -.
DR   eggNOG; KOG2301; Eukaryota.
DR   eggNOG; ENOG410XNP6; LUCA.
DR   GeneTree; ENSGT00830000128242; -.
DR   HOVERGEN; HBG053100; -.
DR   InParanoid; Q15858; -.
DR   KO; K04841; -.
DR   OMA; RQKCPPW; -.
DR   OrthoDB; EOG091G00FK; -.
DR   PhylomeDB; Q15858; -.
DR   TreeFam; TF323985; -.
DR   Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR   Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR   SIGNOR; Q15858; -.
DR   GeneWiki; Nav1.7; -.
DR   GenomeRNAi; 6335; -.
DR   PRO; PR:Q15858; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000169432; -.
DR   CleanEx; HS_SCN9A; -.
DR   ExpressionAtlas; Q15858; baseline and differential.
DR   Genevisible; Q15858; HS.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR   GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR   GO; GO:0001518; C:voltage-gated sodium channel complex; IEA:Ensembl.
DR   GO; GO:0031402; F:sodium ion binding; IEA:Ensembl.
DR   GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB.
DR   GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR   GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR   GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR   GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR   GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR   GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR   GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0006814; P:sodium ion transport; TAS:ProtInc.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR   InterPro; IPR001696; Na_channel_asu.
DR   InterPro; IPR010526; Na_trans_assoc.
DR   InterPro; IPR024583; Na_trans_cytopl.
DR   InterPro; IPR028803; SCN9A.
DR   PANTHER; PTHR10037:SF235; PTHR10037:SF235; 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.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW   Complete proteome; Disease mutation; Disulfide bond; Epilepsy;
KW   Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW   Polymorphism; Reference proteome; Repeat; Sodium; Sodium channel;
KW   Sodium transport; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation; Voltage-gated channel.
FT   CHAIN         1   1988       Sodium channel protein type 9 subunit
FT                                alpha.
FT                                /FTId=PRO_0000048502.
FT   TOPO_DOM      1    126       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    127    145       Helical; Name=S1 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    146    152       Extracellular. {ECO:0000305}.
FT   TRANSMEM    153    173       Helical; Name=S2 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    174    187       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    188    205       Helical; Name=S3 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    206    211       Extracellular. {ECO:0000305}.
FT   TRANSMEM    212    228       Helical; Name=S4 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    229    247       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    248    267       Helical; Name=S5 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    268    346       Extracellular. {ECO:0000305}.
FT   INTRAMEM    347    371       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    372    378       Extracellular. {ECO:0000305}.
FT   TRANSMEM    379    399       Helical; Name=S6 of repeat I.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    400    744       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    745    763       Helical; Name=S1 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    764    774       Extracellular. {ECO:0000305}.
FT   TRANSMEM    775    794       Helical; Name=S2 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    795    808       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    809    828       Helical; Name=S3 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    829    830       Extracellular. {ECO:0000305}.
FT   TRANSMEM    831    848       Helical; Name=S4 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    849    864       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    865    883       Helical; Name=S5 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    884    912       Extracellular. {ECO:0000305}.
FT   INTRAMEM    913    933       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    934    946       Extracellular. {ECO:0000305}.
FT   TRANSMEM    947    967       Helical; Name=S6 of repeat II.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM    968   1193       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1194   1211       Helical; Name=S1 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1212   1224       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1225   1243       Helical; Name=S2 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1244   1257       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1258   1276       Helical; Name=S3 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1277   1284       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1285   1303       Helical; Name=S4 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1304   1320       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1321   1340       Helical; Name=S5 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1341   1392       Extracellular. {ECO:0000305}.
FT   INTRAMEM   1393   1414       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1415   1431       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1432   1453       Helical; Name=S6 of repeat III.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1454   1516       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1517   1534       Helical; Name=S1 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1535   1545       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1546   1564       Helical; Name=S2 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1565   1576       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1577   1594       Helical; Name=S3 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1595   1607       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1608   1624       Helical; Name=S4 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1625   1643       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM   1644   1661       Helical; Name=S5 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1662   1683       Extracellular. {ECO:0000305}.
FT   INTRAMEM   1684   1706       Pore-forming.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1707   1736       Extracellular. {ECO:0000305}.
FT   TRANSMEM   1737   1759       Helical; Name=S6 of repeat IV.
FT                                {ECO:0000250|UniProtKB:D0E0C2}.
FT   TOPO_DOM   1760   1988       Cytoplasmic. {ECO:0000305}.
FT   REPEAT      112    410       I. {ECO:0000305}.
FT   REPEAT      726    989       II. {ECO:0000305}.
FT   REPEAT     1180   1488       III. {ECO:0000305}.
FT   REPEAT     1497   1795       IV. {ECO:0000305}.
FT   DOMAIN     1889   1918       IQ.
FT   MOD_RES     503    503       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O88420}.
FT   MOD_RES     505    505       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O88420}.
FT   MOD_RES    1490   1490       Phosphoserine; by PKC.
FT                                {ECO:0000269|PubMed:25240195}.
FT   CARBOHYD    209    209       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    283    283       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1352   1352       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1366   1366       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1375   1375       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    275    324       {ECO:0000250|UniProtKB:D0E0C2}.
FT   DISULFID    895    895       Interchain; with SCN2B or SCN4B.
FT                                {ECO:0000250|UniProtKB:P04775}.
FT   DISULFID    895    895       Interchain; with the conotoxin GVIIJ
FT                                (when the channel is not linked to SCN2B
FT                                or SCN4B; the bond to SCN2B or SCN4B
FT                                protects the channel from the inhibition
FT                                by toxin).
FT                                {ECO:0000250|UniProtKB:P04775}.
FT   DISULFID    935    944       {ECO:0000250|UniProtKB:D0E0C2}.
FT   VAR_SEQ     200    229       YLTEFVNLGNVSALRTFRVLRALKTISVIP -> YVTEFVD
FT                                LGNVSALRTFRVLRALKTISVIP (in isoform 2 and
FT                                isoform 4).
FT                                {ECO:0000303|PubMed:15302875}.
FT                                /FTId=VSP_012028.
FT   VAR_SEQ     648    658       Missing (in isoform 3 and isoform 4).
FT                                {ECO:0000303|PubMed:15302875,
FT                                ECO:0000303|PubMed:17167479,
FT                                ECO:0000303|PubMed:7720699}.
FT                                /FTId=VSP_012029.
FT   VARIANT      10     10       Q -> R (in PERYTHM; causes a
FT                                hyperpolarizing shift of -5.3 mV for the
FT                                midpoint of activation which is smaller
FT                                than that seen in other mutations causing
FT                                early-onset erythromelalgia mutations;
FT                                also causes a faster rate of activation
FT                                and slower deactivation compared to wild-
FT                                type; expression of the mutant protein
FT                                induced hyperexcitability in dorsal root
FT                                ganglion neurons but the increase is
FT                                smaller than that produced by Thr-859;
FT                                dbSNP:rs267607030).
FT                                {ECO:0000269|PubMed:19369487}.
FT                                /FTId=VAR_064595.
FT   VARIANT      62     62       I -> V (in FEB3B; dbSNP:rs121908920).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064596.
FT   VARIANT     149    149       P -> Q (in FEB3B; dbSNP:rs121908921).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064597.
FT   VARIANT     216    216       F -> S (in PERYTHM; hyperpolarizes the
FT                                voltage dependence of activation by 11
FT                                mV, accelerates activation, slows
FT                                deactivation and enhances the response to
FT                                slow, small depolarizations;
FT                                dbSNP:rs80356469).
FT                                {ECO:0000269|PubMed:15955112,
FT                                ECO:0000269|PubMed:16988069}.
FT                                /FTId=VAR_064598.
FT   VARIANT     228    228       I -> M (in dbSNP:rs71428908).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064599.
FT   VARIANT     241    241       S -> T (in PERYTHM; dbSNP:rs80356470).
FT                                {ECO:0000269|PubMed:16216943}.
FT                                /FTId=VAR_032014.
FT   VARIANT     395    395       N -> K (in PERYTHM; dbSNP:rs80356471).
FT                                {ECO:0000269|PubMed:15955112}.
FT                                /FTId=VAR_064600.
FT   VARIANT     406    406       E -> K (in PERYTHM).
FT                                /FTId=VAR_064601.
FT   VARIANT     490    490       S -> N (in dbSNP:rs58022607).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064602.
FT   VARIANT     519    519       E -> K (in dbSNP:rs187453572).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064603.
FT   VARIANT     641    641       N -> Y (in GEFS+7; dbSNP:rs121908918).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064604.
FT   VARIANT     666    666       K -> R (in GEFS+7; also found in a
FT                                patient with severe myoclonic epilepsy in
FT                                infancy; dbSNP:rs121908919).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064605.
FT   VARIANT     695    695       I -> M (in dbSNP:rs199588089).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064606.
FT   VARIANT     710    710       C -> Y (found in a patient with severe
FT                                myoclonic epilepsy in infancy;
FT                                dbSNP:rs201709980).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064607.
FT   VARIANT     750    750       I -> V (in dbSNP:rs182650126).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064608.
FT   VARIANT     859    859       I -> T (in PERYTHM; sporadic; activated
FT                                at more negative potentials; slower
FT                                inactivation kinetics than wild-type
FT                                channels; dbSNP:rs80356474).
FT                                {ECO:0000269|PubMed:14985375,
FT                                ECO:0000269|PubMed:15385606,
FT                                ECO:0000269|PubMed:15955112,
FT                                ECO:0000269|PubMed:19369487}.
FT                                /FTId=VAR_019947.
FT   VARIANT     869    869       L -> F (in PERYTHM; causes a
FT                                hyperpolarizing shift in channel
FT                                activation, a depolarizing shift of
FT                                inactivation and an 18-fold increase in
FT                                deactivation time compared to wild-type;
FT                                the mean ramp current amplitude in
FT                                response to slow depolarization is higher
FT                                in the mutant channels;
FT                                dbSNP:rs80356476).
FT                                {ECO:0000269|PubMed:15955112,
FT                                ECO:0000269|PubMed:16392115}.
FT                                /FTId=VAR_064609.
FT   VARIANT     869    869       L -> H (in PERYTHM; activated at more
FT                                negative potentials; slower inactivation
FT                                kinetics than wild-type channels;
FT                                dbSNP:rs80356475).
FT                                {ECO:0000269|PubMed:14985375,
FT                                ECO:0000269|PubMed:15385606,
FT                                ECO:0000269|PubMed:16702558}.
FT                                /FTId=VAR_019948.
FT   VARIANT     907    907       R -> Q (in CIP; significant reduction in
FT                                membrane localization of the mutant
FT                                protein compared to the wild-type;
FT                                complete loss of function of the sodium
FT                                channel). {ECO:0000269|PubMed:20635406}.
FT                                /FTId=VAR_064610.
FT   VARIANT     932    932       M -> L (in dbSNP:rs12478318).
FT                                /FTId=VAR_030444.
FT   VARIANT     943    943       M -> L (in dbSNP:rs12478318).
FT                                /FTId=VAR_055646.
FT   VARIANT    1007   1007       R -> C (in PEPD; dbSNP:rs121908910).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032015.
FT   VARIANT    1134   1134       L -> F (in dbSNP:rs200160858).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064611.
FT   VARIANT    1161   1161       W -> R (in dbSNP:rs6746030).
FT                                {ECO:0000269|PubMed:15955112,
FT                                ECO:0000269|PubMed:17167479,
FT                                ECO:0000269|PubMed:7720699}.
FT                                /FTId=VAR_019949.
FT   VARIANT    1171   1171       E -> Q (found in a patient with severe
FT                                myoclonic epilepsy in infancy).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064612.
FT   VARIANT    1278   1278       L -> V (in dbSNP:rs180922748).
FT                                {ECO:0000269|PubMed:19763161}.
FT                                /FTId=VAR_064613.
FT   VARIANT    1309   1309       V -> D (in PEPD; dbSNP:rs121908911).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032016.
FT   VARIANT    1309   1309       V -> F (in PEPD; dbSNP:rs121908912).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032017.
FT   VARIANT    1310   1310       V -> F (in PEPD; dbSNP:rs121908913).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032018.
FT   VARIANT    1381   1385       Missing (in CIP; significant reduction in
FT                                membrane localization of the mutant
FT                                protein compared to the wild-type;
FT                                complete loss of function of the sodium
FT                                channel). {ECO:0000269|PubMed:20635406}.
FT                                /FTId=VAR_064614.
FT   VARIANT    1460   1460       F -> V (in PERYTHM; produces a
FT                                hyperpolarizing shift in channel
FT                                activation and a depolarizing shift in
FT                                steady-state activation;
FT                                dbSNP:rs80356478).
FT                                {ECO:0000269|PubMed:15958509}.
FT                                /FTId=VAR_032019.
FT   VARIANT    1472   1472       I -> T (in PEPD; reduction in fast
FT                                inactivation leading to persistent sodium
FT                                current; dbSNP:rs121908914).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032020.
FT   VARIANT    1473   1473       F -> V (in PEPD).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032021.
FT   VARIANT    1475   1475       T -> I (in PEPD; reduction in fast
FT                                inactivation leading to persistent sodium
FT                                current; dbSNP:rs121908915).
FT                                {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032022.
FT   VARIANT    1623   1623       L -> P (in PEPD; depolarizes the voltage-
FT                                dependence of channel activation and
FT                                steady-state fast inactivation; increases
FT                                ramp current).
FT                                {ECO:0000269|PubMed:25285947}.
FT                                /FTId=VAR_072279.
FT   VARIANT    1638   1638       M -> K (in PEPD; reduction in fast
FT                                inactivation leading to persistent sodium
FT                                current). {ECO:0000269|PubMed:17145499}.
FT                                /FTId=VAR_032023.
FT   VARIANT    1643   1643       A -> E (in PERYTHM and PEPD;
FT                                hyperpolarizes voltage-dependence of
FT                                channel activation; depolarizes the
FT                                voltage-dependence of steady-state fast
FT                                inactivation; slows channel deactivation;
FT                                enhances persistent and resurgent
FT                                current; enhances neuronal
FT                                hyperexcitability in dorsal root ganglion
FT                                neurons; dbSNP:rs879253994).
FT                                {ECO:0000269|PubMed:18945915,
FT                                ECO:0000269|PubMed:24311784}.
FT                                /FTId=VAR_072280.
FT   VARIANT    1643   1643       A -> T (in PERYTHM; no effect on voltage-
FT                                dependence of channel activation;
FT                                depolarizes the voltage dependence of
FT                                steady-state fast inactivation;
FT                                accelerates channel deactivation; no
FT                                increase in persistent and resurgent
FT                                currents; enhances neuronal
FT                                hyperexcitability in dorsal root ganglion
FT                                neurons). {ECO:0000269|PubMed:24311784}.
FT                                /FTId=VAR_072281.
FT   VARIANT    1919   1919       D -> G (in dbSNP:rs3750904).
FT                                /FTId=VAR_019950.
FT   MUTAGEN    1490   1490       S->A: Abolishes stimulation by agents
FT                                that stimulate PKC activity.
FT                                {ECO:0000269|PubMed:25240195}.
FT   MUTAGEN    1490   1490       S->D,E: Increases current amplitude.
FT                                {ECO:0000269|PubMed:25240195}.
FT   MUTAGEN    1643   1643       A->D: Depolarizes the voltage-dependence
FT                                of steady-state fast inactivation;
FT                                enhances persistent current.
FT                                {ECO:0000269|PubMed:24311784}.
FT   MUTAGEN    1643   1643       A->K: No effect on voltage-dependence of
FT                                steady-state fast inactivation.
FT                                {ECO:0000269|PubMed:24311784}.
FT   MUTAGEN    1643   1643       A->V: No effect on voltage-dependence of
FT                                steady-state fast inactivation.
FT                                {ECO:0000269|PubMed:24311784}.
FT   CONFLICT    267    267       F -> S (in Ref. 4; AAT85834).
FT                                {ECO:0000305}.
FT   CONFLICT    301    301       K -> R (in Ref. 4; AAT85835).
FT                                {ECO:0000305}.
FT   CONFLICT    309    309       S -> P (in Ref. 4; AAT85834).
FT                                {ECO:0000305}.
FT   CONFLICT    420    420       E -> G (in Ref. 4; AAT85834).
FT                                {ECO:0000305}.
FT   CONFLICT    430    430       L -> P (in Ref. 4; AAT85834).
FT                                {ECO:0000305}.
FT   CONFLICT    501    501       S -> P (in Ref. 4; AAT85835).
FT                                {ECO:0000305}.
FT   CONFLICT    610    610       P -> T (in Ref. 4; AAT85835).
FT                                {ECO:0000305}.
FT   CONFLICT    642    642       G -> R (in Ref. 4; AAT85835).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1988 AA;  226372 MW;  1BAEB8F32EBF5438 CRC64;
     MAMLPPPGPQ SFVHFTKQSL ALIEQRIAER KSKEPKEEKK DDDEEAPKPS SDLEAGKQLP
     FIYGDIPPGM VSEPLEDLDP YYADKKTFIV LNKGKTIFRF NATPALYMLS PFSPLRRISI
     KILVHSLFSM LIMCTILTNC IFMTMNNPPD WTKNVEYTFT GIYTFESLVK ILARGFCVGE
     FTFLRDPWNW LDFVVIVFAY LTEFVNLGNV SALRTFRVLR ALKTISVIPG LKTIVGALIQ
     SVKKLSDVMI LTVFCLSVFA LIGLQLFMGN LKHKCFRNSL ENNETLESIM NTLESEEDFR
     KYFYYLEGSK DALLCGFSTD SGQCPEGYTC VKIGRNPDYG YTSFDTFSWA FLALFRLMTQ
     DYWENLYQQT LRAAGKTYMI FFVVVIFLGS FYLINLILAV VAMAYEEQNQ ANIEEAKQKE
     LEFQQMLDRL KKEQEEAEAI AAAAAEYTSI RRSRIMGLSE SSSETSKLSS KSAKERRNRR
     KKKNQKKLSS GEEKGDAEKL SKSESEDSIR RKSFHLGVEG HRRAHEKRLS TPNQSPLSIR
     GSLFSARRSS RTSLFSFKGR GRDIGSETEF ADDEHSIFGD NESRRGSLFV PHRPQERRSS
     NISQASRSPP MLPVNGKMHS AVDCNGVVSL VDGRSALMLP NGQLLPEVII DKATSDDSGT
     TNQIHKKRRC SSYLLSEDML NDPNLRQRAM SRASILTNTV EELEESRQKC PPWWYRFAHK
     FLIWNCSPYW IKFKKCIYFI VMDPFVDLAI TICIVLNTLF MAMEHHPMTE EFKNVLAIGN
     LVFTGIFAAE MVLKLIAMDP YEYFQVGWNI FDSLIVTLSL VELFLADVEG LSVLRSFRLL
     RVFKLAKSWP TLNMLIKIIG NSVGALGNLT LVLAIIVFIF AVVGMQLFGK SYKECVCKIN
     DDCTLPRWHM NDFFHSFLIV FRVLCGEWIE TMWDCMEVAG QAMCLIVYMM VMVIGNLVVL
     NLFLALLLSS FSSDNLTAIE EDPDANNLQI AVTRIKKGIN YVKQTLREFI LKAFSKKPKI
     SREIRQAEDL NTKKENYISN HTLAEMSKGH NFLKEKDKIS GFGSSVDKHL MEDSDGQSFI
     HNPSLTVTVP IAPGESDLEN MNAEELSSDS DSEYSKVRLN RSSSSECSTV DNPLPGEGEE
     AEAEPMNSDE PEACFTDGCV WRFSCCQVNI ESGKGKIWWN IRKTCYKIVE HSWFESFIVL
     MILLSSGALA FEDIYIERKK TIKIILEYAD KIFTYIFILE MLLKWIAYGY KTYFTNAWCW
     LDFLIVDVSL VTLVANTLGY SDLGPIKSLR TLRALRPLRA LSRFEGMRVV VNALIGAIPS
     IMNVLLVCLI FWLIFSIMGV NLFAGKFYEC INTTDGSRFP ASQVPNRSEC FALMNVSQNV
     RWKNLKVNFD NVGLGYLSLL QVATFKGWTI IMYAAVDSVN VDKQPKYEYS LYMYIYFVVF
     IIFGSFFTLN LFIGVIIDNF NQQKKKLGGQ DIFMTEEQKK YYNAMKKLGS KKPQKPIPRP
     GNKIQGCIFD LVTNQAFDIS IMVLICLNMV TMMVEKEGQS QHMTEVLYWI NVVFIILFTG
     ECVLKLISLR HYYFTVGWNI FDFVVVIISI VGMFLADLIE TYFVSPTLFR VIRLARIGRI
     LRLVKGAKGI RTLLFALMMS LPALFNIGLL LFLVMFIYAI FGMSNFAYVK KEDGINDMFN
     FETFGNSMIC LFQITTSAGW DGLLAPILNS KPPDCDPKKV HPGSSVEGDC GNPSVGIFYF
     VSYIIISFLV VVNMYIAVIL ENFSVATEES TEPLSEDDFE MFYEVWEKFD PDATQFIEFS
     KLSDFAAALD PPLLIAKPNK VQLIAMDLPM VSGDRIHCLD ILFAFTKRVL GESGEMDSLR
     SQMEERFMSA NPSKVSYEPI TTTLKRKQED VSATVIQRAY RRYRLRQNVK NISSIYIKDG
     DRDDDLLNKK DMAFDNVNEN SSPEKTDATS STTSPPSYDS VTKPDKEKYE QDRTEKEDKG
     KDSKESKK
//
DBGET integrated database retrieval system