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Aliases for SCN8A Gene

Aliases for SCN8A Gene

  • Sodium Voltage-Gated Channel Alpha Subunit 8 2 3
  • Sodium Channel, Voltage Gated, Type VIII Alpha Subunit 2 3 5
  • Sodium Channel, Voltage Gated, Type VIII, Alpha Subunit 2 3
  • Voltage-Gated Sodium Channel Subunit Alpha Nav1.6 3 4
  • MED 3 4
  • Sodium Channel, Voltage Gated, Type VIII, Alpha Polypeptide 2
  • Voltage-Gated Sodium Channel Type VIII Alpha Protein 3
  • Sodium Channel Protein Type VIII Subunit Alpha 4
  • HNa6/Scn8a Voltage-Gated Sodium Channel 3
  • CERIII 3
  • EIEE13 3
  • Nav1.6 3
  • NaCh6 3
  • CIAT 3
  • PN4 3

External Ids for SCN8A Gene

Previous HGNC Symbols for SCN8A Gene

  • MED

Previous GeneCards Identifiers for SCN8A Gene

  • GC12M052742
  • GC12P052007
  • GC12P051701
  • GC12P050271
  • GC12P049089
  • GC12P051987

Summaries for SCN8A Gene

Entrez Gene Summary for SCN8A 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 mental retardation, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

GeneCards Summary for SCN8A Gene

SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8) is a Protein Coding gene. Diseases associated with SCN8A include epileptic encephalopathy, early infantile, 13 and cognitive impairment with or without cerebellar ataxia. Among its related pathways are Cardiac conduction and Developmental Biology. GO annotations related to this gene include ion channel activity and voltage-gated sodium channel activity. An important paralog of this gene is CACNA1G.

UniProtKB/Swiss-Prot for SCN8A Gene

  • Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.

Tocris Summary for SCN8A Gene

  • Voltage-gated sodium channels (NaV) are responsible for action potential initiation and propagation in excitable cells, including nerve, muscle, and neuroendocrine cell types. They are also expressed at low levels in non-excitable cells, where their physiological role is unclear.

Gene Wiki entry for SCN8A Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SCN8A Gene

Genomics for SCN8A Gene

Regulatory Elements for SCN8A Gene

Promoters for SCN8A Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around SCN8A on UCSC Golden Path with GeneCards custom track

Genomic Location for SCN8A Gene

Chromosome:
12
Start:
51,590,193 bp from pter
End:
51,812,864 bp from pter
Size:
222,672 bases
Orientation:
Plus strand

Genomic View for SCN8A Gene

Genes around SCN8A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SCN8A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SCN8A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SCN8A Gene

Proteins for SCN8A Gene

  • Protein details for SCN8A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UQD0-SCN8A_HUMAN
    Recommended name:
    Sodium channel protein type 8 subunit alpha
    Protein Accession:
    Q9UQD0
    Secondary Accessions:
    • B9VWG8
    • O95788
    • Q9NYX2
    • Q9UPB2

    Protein attributes for SCN8A Gene

    Size:
    1980 amino acids
    Molecular mass:
    225280 Da
    Quaternary structure:
    • Interacts with NEDD4 and NEDD4L (By similarity). Interacts with FGF13; may regulate SCN8A activity.

    Alternative splice isoforms for SCN8A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SCN8A Gene

Proteomics data for SCN8A Gene at MOPED

Post-translational modifications for SCN8A Gene

  • May be ubiquitinated by NEDD4L; which would promote its endocytosis.
  • Phosphorylation at Ser-1497 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
  • Glycosylation at Asn 215, Asn 289, Asn 295, Asn 308, Asn 326, Asn 1358, Asn 1372, and Asn 1383
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for SCN8A (SCN8A)

No data available for DME Specific Peptides for SCN8A Gene

Domains & Families for SCN8A Gene

Gene Families for SCN8A Gene

Graphical View of Domain Structure for InterPro Entry

Q9UQD0

UniProtKB/Swiss-Prot:

SCN8A_HUMAN :
  • The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
  • Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.
Domain:
  • The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
  • Contains 1 IQ domain.
Family:
  • Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.
genes like me logo Genes that share domains with SCN8A: view

Function for SCN8A Gene

Molecular function for SCN8A Gene

GENATLAS Biochemistry:
sodium voltage-gated channel,type VIII,alpha polypeptide,with two alternative spliced isoforms,expressed in brain and spinal cord,homolog to the Scn8a murine gene,mutated in motor end-plate disease
UniProtKB/Swiss-Prot Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
genes like me logo Genes that share phenotypes with SCN8A: view

Human Phenotype Ontology for SCN8A Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Animal Models , Transcription Factor Targets and HOMER Transcription for SCN8A Gene

Localization for SCN8A Gene

Subcellular locations from UniProtKB/Swiss-Prot for SCN8A Gene

Membrane; Multi-pass membrane protein.
Isoform 5: Cytoplasmic vesicle. Note=Some vesicles are localized adjacent to melanoma invadopodia and macrophage podosomes. Does not localize to the plasma membrane.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SCN8A Gene COMPARTMENTS Subcellular localization image for SCN8A gene
Compartment Confidence
plasma membrane 5
cytosol 1
nucleus 1

Gene Ontology (GO) - Cellular Components for SCN8A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016020 membrane IEA --
GO:0033268 node of Ranvier ISS --
genes like me logo Genes that share ontologies with SCN8A: view

Pathways & Interactions for SCN8A Gene

genes like me logo Genes that share pathways with SCN8A: view

Gene Ontology (GO) - Biological Process for SCN8A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007422 peripheral nervous system development ISS --
GO:0019228 neuronal action potential IBA --
GO:0055085 transmembrane transport IEA --
GO:0086010 membrane depolarization during action potential IBA --
genes like me logo Genes that share ontologies with SCN8A: view

No data available for SIGNOR curated interactions for SCN8A Gene

Drugs & Compounds for SCN8A Gene

(12) Drugs for SCN8A Gene - From: DGIdb, IUPHAR, Tocris, DrugBank, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Valproic Acid Approved, Investigational Pharma Target HDAC1 inhibitor, Histone deacetylase (HDAC)inhibitors 311
Tetrodotoxin Investigational Pharma Channel blocker, blocker, Target 4
Veratridine Pharma Activator Voltage-gated Na+ channel opener 0
AFT-II Pharma Antagonist, Gating inhibitor 0
ATX-II Pharma Antagonist, Gating inhibitor 0

(5) Additional Compounds for SCN8A Gene - From: Tocris, IUPHAR, Novoseek, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Sodium
  • Sodium ion
7440-23-5
beta-scorpion toxin Cn2
Activator
Amiloride hydrochloride
2016-88-8
Flunarizine dihydrochloride
30484-77-6
Riluzole hydrochloride
850608-87-6

(5) Tocris Compounds for SCN8A Gene

Compound Action Cas Number
Amiloride hydrochloride Na+ channel blocker; also I2 imidazoline ligand 2016-88-8
Flunarizine dihydrochloride Dual Na+/Ca2+ channel (T-type) blocker 30484-77-6
Riluzole hydrochloride Glutamate release inhibitor/GABA uptake inhibitor 850608-87-6
Veratridine Voltage-gated Na+ channel opener 71-62-5
Vinpocetine Na+ channel blocker 42971-09-5
genes like me logo Genes that share compounds with SCN8A: view

Transcripts for SCN8A Gene

Alternative Splicing Database (ASD) splice patterns (SP) for SCN8A Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20 ^ 21 ^ 22a ·
SP1: - - -
SP2: -
SP3: - -
SP4: -
SP5: -

ExUns: 22b ^ 23 ^ 24 ^ 25 ^ 26 ^ 27
SP1:
SP2:
SP3:
SP4:
SP5:

Relevant External Links for SCN8A Gene

GeneLoc Exon Structure for
SCN8A
ECgene alternative splicing isoforms for
SCN8A

Expression for SCN8A Gene

mRNA expression in normal human tissues for SCN8A Gene

mRNA differential expression in normal tissues according to GTEx for SCN8A Gene

This gene is overexpressed in Brain - Frontal Cortex (BA9) (x6.8), Brain - Cerebellar Hemisphere (x6.2), Brain - Cerebellum (x4.9), and Brain - Anterior cingulate cortex (BA24) (x4.9).

Protein differential expression in normal tissues from HIPED for SCN8A Gene

This gene is overexpressed in Frontal cortex (44.1), Adipocyte (12.4), and Platelet (11.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SCN8A Gene



SOURCE GeneReport for Unigene cluster for SCN8A Gene Hs.436550

mRNA Expression by UniProt/SwissProt for SCN8A Gene

Q9UQD0-SCN8A_HUMAN
Tissue specificity: Isoform 5 is expressed in non-neuronal tissues, such as monocytes/macrophages.
genes like me logo Genes that share expression patterns with SCN8A: view

Protein tissue co-expression partners for SCN8A Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for SCN8A Gene

Orthologs for SCN8A Gene

This gene was present in the common ancestor of animals.

Orthologs for SCN8A Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia SCN8A 35
  • 94.43 (n)
  • 99.55 (a)
SCN8A 36
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SCN8A 35
  • 95.4 (n)
  • 99.39 (a)
SCN8A 36
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Scn8a 35
  • 90.07 (n)
  • 98.74 (a)
Scn8a 16
Scn8a 36
  • 99 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia SCN8A 35
  • 99.21 (n)
  • 99.53 (a)
rat
(Rattus norvegicus)
Mammalia Scn8a 35
  • 90.71 (n)
  • 98.69 (a)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 59 (a)
OneToMany
-- 36
  • 92 (a)
OneToMany
chicken
(Gallus gallus)
Aves SCN8A 35
  • 83.86 (n)
  • 94.23 (a)
SCN8A 36
  • 94 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SCN8A 36
  • 93 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC101731347 35
  • 77.15 (n)
  • 88.09 (a)
zebrafish
(Danio rerio)
Actinopterygii scn8a 35
scn8ab 35
  • 75.98 (n)
  • 84.28 (a)
scn8aa 36
  • 84 (a)
OneToMany
scn8ab 36
  • 84 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta NaCP60E 37
  • 63 (a)
para 37
  • 45 (a)
Species with no ortholog for SCN8A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SCN8A Gene

ENSEMBL:
Gene Tree for SCN8A (if available)
TreeFam:
Gene Tree for SCN8A (if available)

Paralogs for SCN8A Gene

genes like me logo Genes that share paralogs with SCN8A: view

Variants for SCN8A Gene

Sequence variations from dbSNP and Humsavar for SCN8A Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
VAR_067539 Epileptic encephalopathy, early infantile, 13 (EIEE13)
VAR_071674 Epileptic encephalopathy, early infantile, 13 (EIEE13)
VAR_071675 Epileptic encephalopathy, early infantile, 13 (EIEE13)
VAR_071676 Epileptic encephalopathy, early infantile, 13 (EIEE13)
VAR_071677 Epileptic encephalopathy, early infantile, 13 (EIEE13)

Structural Variations from Database of Genomic Variants (DGV) for SCN8A Gene

Variant ID Type Subtype PubMed ID
esv2020985 CNV Deletion 18987734
esv2745886 CNV Deletion 23290073
esv2745887 CNV Deletion 23290073
nsv706 CNV Loss 18451855
nsv826373 CNV Gain 20364138

Variation tolerance for SCN8A Gene

Residual Variation Intolerance Score: 0.645% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.17; 39.31% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SCN8A Gene

HapMap Linkage Disequilibrium report
SCN8A
Human Gene Mutation Database (HGMD)
SCN8A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SCN8A Gene

Disorders for SCN8A Gene

MalaCards: The human disease database

(17) MalaCards diseases for SCN8A Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
epileptic encephalopathy, early infantile, 13
  • eiee13
cognitive impairment with or without cerebellar ataxia
  • ciat
pseudoachondroplasia
  • pseudoachondroplastic dysplasia
epiphyseal dysplasia, multiple, 1
  • epiphyseal dysplasia, multiple 1
pulpitis
  • pulpitis nos
- elite association - COSMIC cancer census association via MalaCards
Search SCN8A in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SCN8A_HUMAN
  • Cognitive impairment with or without cerebellar ataxia (CIAT) [MIM:614306]: A disorder characterized by markedly delayed cognitive and motor development, attention deficit disorder, and cerebellar ataxia. Features include bilateral esophoria, strabismatic amblyopia, unsustained gaze evoked nystagmus on horizontal gaze, ataxic gait, dysmetria in the upper limbs and dysarthria, with normal strength, tone, and reflexes. {ECO:0000269 PubMed:16236810}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Epileptic encephalopathy, early infantile, 13 (EIEE13) [MIM:614558]: A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. EIEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy. {ECO:0000269 PubMed:22365152, ECO:0000269 PubMed:24352161, ECO:0000269 PubMed:24874546, ECO:0000269 PubMed:24888894, ECO:0000269 PubMed:25239001}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SCN8A

Genetic Association Database (GAD)
SCN8A
Human Genome Epidemiology (HuGE) Navigator
SCN8A
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SCN8A
genes like me logo Genes that share disorders with SCN8A: view

No data available for Genatlas for SCN8A Gene

Publications for SCN8A Gene

  1. Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A. (PMID: 9828131) Plummer N.W. … Meisler M.H. (Genomics 1998) 2 3 4 67
  2. Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. (PMID: 7670495) Burgess D.L. … Meisler M.H. (Nat. Genet. 1995) 2 3 23
  3. Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremor. (PMID: 18718804) Sharkey L.M. … Meisler M.H. (Parkinsonism Relat. Disord. 2009) 3 23
  4. Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A. (PMID: 19136557) Carrithers M.D. … Waxman S.G. (J. Biol. Chem. 2009) 3 23
  5. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. (PMID: 16382098) Catterall W.A. … Waxman S.G. (Pharmacol. Rev. 2005) 2 3

Products for SCN8A Gene

Sources for SCN8A Gene

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