Seroatlas · Human Serome Atlas

SCN8A

Sodium channel protein type 8 subunit alpha

Also known as: CerIII, CIAT, MED, NaCh6, Nav1.6, PN4, SCN8A_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9UQD0
Gene: SCN8A
Ensembl: ENSG00000196876
Chromosome: 12
Canonical length: 1980 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters, Voltage-gated ion channels
Subcellular location: Vesicles,Plasma membrane,Cell Junctions

OverviewNCBI Gene

This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with cognitive disability, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

1980 residues, UniProt reviewed canonical sequence.

>Q9UQD0|SCN8A
     1  MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE
    61  AGKSLPFIYG DIPQGLVAVP LEDFDPYYLT QKTFVVLNRG KTLFRFSATP ALYILSPFNL
   121  IRRIAIKILI HSVFSMIIMC TILTNCVFMT FSNPPDWSKN VEYTFTGIYT FESLVKIIAR
   181  GFCIDGFTFL RDPWNWLDFS VIMMAYITEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI
   241  VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLRNK CVVWPINFNE SYLENGTKGF
   301  DWEEYINNKT NFYTVPGMLE PLLCGNSSDA GQCPEGYQCM KAGRNPNYGY TSFDTFSWAF
   361  LALFRLMTQD YWENLYQLTL RAAGKTYMIF FVLVIFVGSF YLVNLILAVV AMAYEEQNQA
   421  TLEEAEQKEA EFKAMLEQLK KQQEEAQAAA MATSAGTVSE DAIEEEGEEG GGSPRSSSEI
   481  SKLSSKSAKE RRNRRKKRKQ KELSEGEEKG DPEKVFKSES EDGMRRKAFR LPDNRIGRKF
   541  SIMNQSLLSI PGSPFLSRHN SKSSIFSFRG PGRFRDPGSE NEFADDEHST VEESEGRRDS
   601  LFIPIRARER RSSYSGYSGY SQGSRSSRIF PSLRRSVKRN STVDCNGVVS LIGGPGSHIG
   661  GRLLPEATTE VEIKKKGPGS LLVSMDQLAS YGRKDRINSI MSVVTNTLVE ELEESQRKCP
   721  PCWYKFANTF LIWECHPYWI KLKEIVNLIV MDPFVDLAIT ICIVLNTLFM AMEHHPMTPQ
   781  FEHVLAVGNL VFTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL
   841  SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIFA VVGMQLFGKS
   901  YKECVCKINQ DCELPRWHMH DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLIVFMMV
   961  MVIGNLVVLN LFLALLLSSF SADNLAATDD DGEMNNLQIS VIRIKKGVAW TKLKVHAFMQ
  1021  AHFKQREADE VKPLDELYEK KANCIANHTG ADIHRNGDFQ KNGNGTTSGI GSSVEKYIID
  1081  EDHMSFINNP NLTVRVPIAV GESDFENLNT EDVSSESDPE GSKDKLDDTS SSEGSTIDIK
  1141  PEVEEVPVEQ PEEYLDPDAC FTEGCVQRFK CCQVNIEEGL GKSWWILRKT CFLIVEHNWF
  1201  ETFIIFMILL SSGALAFEDI YIEQRKTIRT ILEYADKVFT YIFILEMLLK WTAYGFVKFF
  1261  TNAWCWLDFL IVAVSLVSLI ANALGYSELG AIKSLRTLRA LRPLRALSRF EGMRVVVNAL
  1321  VGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKYHYCFNET SEIRFEIEDV NNKTECEKLM
  1381  EGNNTEIRWK NVKINFDNVG AGYLALLQVA TFKGWMDIMY AAVDSRKPDE QPKYEDNIYM
  1441  YIYFVIFIIF GSFFTLNLFI GVIIDNFNQQ KKKFGGQDIF MTEEQKKYYN AMKKLGSKKP
  1501  QKPIPRPLNK IQGIVFDFVT QQAFDIVIMM LICLNMVTMM VETDTQSKQM ENILYWINLV
  1561  FVIFFTCECV LKMFALRHYY FTIGWNIFDF VVVILSIVGM FLADIIEKYF VSPTLFRVIR
  1621  LARIGRILRL IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA
  1681  GIDDMFNFET FGNSMICLFQ ITTSAGWDGL LLPILNRPPD CSLDKEHPGS GFKGDCGNPS
  1741  VGIFFFVSYI IISFLIVVNM YIAIILENFS VATEESADPL SEDDFETFYE IWEKFDPDAT
  1801  QFIEYCKLAD FADALEHPLR VPKPNTIELI AMDLPMVSGD RIHCLDILFA FTKRVLGDSG
  1861  ELDILRQQME ERFVASNPSK VSYEPITTTL RRKQEEVSAV VLQRAYRGHL ARRGFICKKT
  1921  TSNKLENGGT HREKKESTPS TASLPSYDSV TKPEKEKQQR AEEGRRERAK RQKEVRESKC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SCN8A 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: 17 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 17 nTPM
cerebral cortex: 16 nTPM
hippocampal formation: 8.9 nTPM
retina: 7.3 nTPM
basal ganglia: 7 nTPM
pituitary gland: 6.3 nTPM

Single-cell type

brain excitatory neurons: 367 nCPM
brain inhibitory neurons: 321 nCPM
thyrotrophs: 256 nCPM
gonadotrophs: 256 nCPM
somatotrophs: 251 nCPM
lactotrophs: 246 nCPM

Immune cell

basophil: 0.4 nTPM
neutrophil: 0.4 nTPM
eosinophil: 0.1 nTPM
gdT-cell: 0.1 nTPM
memory B-cell: 0.1 nTPM
memory CD4 T-cell: 0.1 nTPM

Brain region

cerebral cortex: 130 nTPM
white matter: 79 nTPM
hippocampal formation: 78 nTPM
pons: 61 nTPM
basal ganglia: 60 nTPM
medulla oblongata: 55 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SCN8A.

Disease | AllUniProt

Conditions SCN8A is implicated in, by any mechanism.

Cognitive impairment with or without cerebellar ataxia (CIAT) MIM:614306
Developmental and epileptic encephalopathy 13 (DEE13) MIM:614558
Seizures, benign familial infantile, 5 (BFIS5) MIM:617080
Myoclonus, familial, 2 (MYOCL2) MIM:618364

Disease | GeneticClinVar

373 pathogenic / likely-pathogenic of 2,545 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Early-infantile DEE
Developmental and epileptic encephalopathy, 13
Cognitive impairment with or without cerebellar ataxia
Complex neurodevelopmental disorder
Seizures, benign familial infantile, 5

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): 0.13
gnomAD pLI: 1
gnomAD missense Z: 7.64
DepMap mean gene effect: -0.15
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SCN8A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SCN8A as an antibody target. Whether an autoantibody or antibody against SCN8A could matter depends on whether native SCN8A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SCN8A is annotated at the cell surface, where native SCN8A is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SCN8A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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