SCN1A

Protein identityUniProt · HPA

UniProt accession

P35498

Gene

SCN1A

Ensembl

ENSG00000144285

Chromosome

2

Canonical length

2009 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters, Voltage-gated ion channels

Subcellular location

Nucleoplasm,Nuclear bodies,Plasma membrane

OverviewNCBI Gene

Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

2009 residues, UniProt reviewed canonical sequence.

>P35498|SCN1A
     1  MEQTVLVPPG PDSFNFFTRE SLAAIERRIA EEKAKNPKPD KKDDDENGPK PNSDLEAGKN
    61  LPFIYGDIPP EMVSEPLEDL DPYYINKKTF IVLNKGKAIF RFSATSALYI LTPFNPLRKI
   121  AIKILVHSLF SMLIMCTILT NCVFMTMSNP PDWTKNVEYT FTGIYTFESL IKIIARGFCL
   181  EDFTFLRDPW NWLDFTVITF AYVTEFVDLG NVSALRTFRV LRALKTISVI PGLKTIVGAL
   241  IQSVKKLSDV MILTVFCLSV FALIGLQLFM GNLRNKCIQW PPTNASLEEH SIEKNITVNY
   301  NGTLINETVF EFDWKSYIQD SRYHYFLEGF LDALLCGNSS DAGQCPEGYM CVKAGRNPNY
   361  GYTSFDTFSW AFLSLFRLMT QDFWENLYQL TLRAAGKTYM IFFVLVIFLG SFYLINLILA
   421  VVAMAYEEQN QATLEEAEQK EAEFQQMIEQ LKKQQEAAQQ AATATASEHS REPSAAGRLS
   481  DSSSEASKLS SKSAKERRNR RKKRKQKEQS GGEEKDEDEF QKSESEDSIR RKGFRFSIEG
   541  NRLTYEKRYS SPHQSLLSIR GSLFSPRRNS RTSLFSFRGR AKDVGSENDF ADDEHSTFED
   601  NESRRDSLFV PRRHGERRNS NLSQTSRSSR MLAVFPANGK MHSTVDCNGV VSLVGGPSVP
   661  TSPVGQLLPE VIIDKPATDD NGTTTETEMR KRRSSSFHVS MDFLEDPSQR QRAMSIASIL
   721  TNTVEELEES RQKCPPCWYK FSNIFLIWDC SPYWLKVKHV VNLVVMDPFV DLAITICIVL
   781  NTLFMAMEHY PMTDHFNNVL TVGNLVFTGI FTAEMFLKII AMDPYYYFQE GWNIFDGFIV
   841  TLSLVELGLA NVEGLSVLRS FRLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII
   901  VFIFAVVGMQ LFGKSYKDCV CKIASDCQLP RWHMNDFFHS FLIVFRVLCG EWIETMWDCM
   961  EVAGQAMCLT VFMMVMVIGN LVVLNLFLAL LLSSFSADNL AATDDDNEMN NLQIAVDRMH
  1021  KGVAYVKRKI YEFIQQSFIR KQKILDEIKP LDDLNNKKDS CMSNHTAEIG KDLDYLKDVN
  1081  GTTSGIGTGS SVEKYIIDES DYMSFINNPS LTVTVPIAVG ESDFENLNTE DFSSESDLEE
  1141  SKEKLNESSS SSEGSTVDIG APVEEQPVVE PEETLEPEAC FTEGCVQRFK CCQINVEEGR
  1201  GKQWWNLRRT CFRIVEHNWF ETFIVFMILL SSGALAFEDI YIDQRKTIKT MLEYADKVFT
  1261  YIFILEMLLK WVAYGYQTYF TNAWCWLDFL IVDVSLVSLT ANALGYSELG AIKSLRTLRA
  1321  LRPLRALSRF EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCINTT
  1381  TGDRFDIEDV NNHTDCLKLI ERNETARWKN VKVNFDNVGF GYLSLLQVAT FKGWMDIMYA
  1441  AVDSRNVELQ PKYEESLYMY LYFVIFIIFG SFFTLNLFIG VIIDNFNQQK KKFGGQDIFM
  1501  TEEQKKYYNA MKKLGSKKPQ KPIPRPGNKF QGMVFDFVTR QVFDISIMIL ICLNMVTMMV
  1561  ETDDQSEYVT TILSRINLVF IVLFTGECVL KLISLRHYYF TIGWNIFDFV VVILSIVGMF
  1621  LAELIEKYFV SPTLFRVIRL ARIGRILRLI KGAKGIRTLL FALMMSLPAL FNIGLLLFLV
  1681  MFIYAIFGMS NFAYVKREVG IDDMFNFETF GNSMICLFQI TTSAGWDGLL APILNSKPPD
  1741  CDPNKVNPGS SVKGDCGNPS VGIFFFVSYI IISFLVVVNM YIAVILENFS VATEESAEPL
  1801  SEDDFEMFYE VWEKFDPDAT QFMEFEKLSQ FAAALEPPLN LPQPNKLQLI AMDLPMVSGD
  1861  RIHCLDILFA FTKRVLGESG EMDALRIQME ERFMASNPSK VSYQPITTTL KRKQEEVSAV
  1921  IIQRAYRRHL LKRTVKQASF TYNKNKIKGG ANLLIKEDMI IDRINENSIT EKTDLTMSTA
  1981  ACPPSYDRVT KPIVEKHEQE GKDEKAKGK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SCN1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

24

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

7.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SCN1A.

Disease | AllUniProt

Conditions SCN1A is implicated in, by any mechanism.

• Generalized epilepsy with febrile seizures plus 2 (GEFSP2) MIM:604403
• Dravet syndrome (DRVT) MIM:607208
• Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC) MIM:607208
• Migraine, familial hemiplegic, 3 (FHM3) MIM:609634
• Febrile seizures, familial, 3A (FEB3A) MIM:604403
• Developmental and epileptic encephalopathy 6B (DEE6B) MIM:619317

Disease | GeneticClinVar

2,125 pathogenic / likely-pathogenic of 5,223 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Early-infantile DEE
• Severe myoclonic epilepsy in infancy
• Generalized epilepsy with febrile seizures plus, type 2
• Developmental and epileptic encephalopathy
• Migraine, familial hemiplegic, 3

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.07

gnomAD pLI

1

gnomAD missense Z

5.22

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult walking behavior
• cardiac muscle cell action potential involved in contraction
• detection of mechanical stimulus involved in sensory perception of pain
• determination of adult lifespan
• establishment of localization in cell
• membrane depolarization during action potential
• nerve development
• neuromuscular process controlling posture
• neuronal action potential
• neuronal action potential propagation
• sodium ion transmembrane transport
• sodium ion transport

Molecular functions

• voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
• voltage-gated sodium channel activity

Cellular components

• axon initial segment
• intercalated disc
• neuronal cell body
• node of Ranvier
• nuclear body
• nucleoplasm
• plasma membrane
• T-tubule
• voltage-gated sodium channel complex
• Z disc

Protein domainsUniProt · Pfam · InterPro

• Voltage gated sodium channel, alpha subunit
• Ion transport domain
• Sodium ion transport-associated domain
• Voltage-gated Na+ ion channel, cytoplasmic domain
• Voltage-dependent channel domain superfamily
• Voltage-gated cation channel calcium and sodium
• Voltage-gated sodium channel alpha subunit, inactivation gate
• SCN5A-like, C-terminal IQ motif
• Ion transport protein
• Sodium ion transport-associated
• Cytoplasmic domain of voltage-gated Na+ ion channel
• SCN5A-like, C-terminal IQ motif
• Voltage gated sodium channel, alpha-1 subunit

KeywordsUniProt

• Autism
• Autism spectrum disorder
• Cell membrane
• Disulfide bond
• Epilepsy
• Glycoprotein
• Ion channel
• Ion transport
• Membrane
• Phosphoprotein
• Repeat
• Sodium
• Sodium channel
• Sodium transport
• Transmembrane
• Transmembrane helix
• Transport
• Voltage-gated channel

InteractionsUniProt · HPA

Protein binding partners of SCN1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FGF13
• TMEM233
• SCN4B
• SCN1B
• SCN2B