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Aliases for SCN8A Gene

Aliases for SCN8A Gene

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

External Ids for SCN8A Gene

Previous Symbols for SCN8A Gene

  • MED

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 Channel, Voltage Gated, Type VIII Alpha Subunit) is a Protein Coding gene. Diseases associated with SCN8A include cognitive impairment with or without cerebellar ataxia and epileptic encephalopathy, early infantile, 13. Among its related pathways are L1CAM interactions and Activation of cAMP-Dependent PKA. GO annotations related to this gene include voltage-gated sodium channel activity. An important paralog of this gene is CACNA1D.

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. Structurally, Nav channels are composed of one pore-forming alpha-subunit, which may be associated with either one or more beta-subunits. alpha-subunits are composed for four homologous domains, each of which contains six transmembrane segments. The fourth transmembrane loop (S4) acts as the voltage sensor and is activated by changes in membrane potential. S4 is also involved in channel gating.

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

Genomic Location for SCN8A Gene

Start:
51,590,266 bp from pter
End:
51,812,864 bp from pter
Size:
222,599 bases
Orientation:
Plus strand

Genomic View for SCN8A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SCN8A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SCN8A Gene

Regulatory Elements 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.
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn215, Asn289, Asn295, Asn308, Asn326, Asn1358, Asn1372, and Asn1383

Other Protein References for SCN8A Gene

No data available for DME Specific Peptides for SCN8A Gene

Domains for SCN8A Gene

Gene Families for SCN8A Gene

HGNC:
  • SC :Sodium channels
  • SCN :Voltage-gated ion channels / Sodium channels
IUPHAR :

Graphical View of Domain Structure for InterPro Entry

Q9UQD0

UniProtKB/Swiss-Prot:

SCN8A_HUMAN
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.:
    • Q9UQD0
  • Contains 1 IQ domain.:
    • Q9UQD0
Family:
  • Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.:
    • Q9UQD0
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.

Gene Ontology (GO) - Molecular Function for SCN8A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity --
GO:0005248 voltage-gated sodium channel activity NAS 9828131
GO:0005515 protein binding --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with SCN8A: view
genes like me logo Genes that share phenotypes with SCN8A: view

No data available for Enzyme Numbers (IUBMB) , Animal Models , miRNA , Transcription Factor Targeting 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 4
cytoskeleton 1
cytosol 1
extracellular 1
nucleus 1

Gene Ontology (GO) - Cellular Components for SCN8A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001518 voltage-gated sodium channel complex IC 9828131
GO:0005886 plasma membrane IBA --
GO:0016020 membrane --
GO:0016021 integral component of membrane TAS 9828131
GO:0016023 cytoplasmic membrane-bounded vesicle IEA --
genes like me logo Genes that share ontologies with SCN8A: view

Pathways 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:0006811 ion transport --
GO:0006814 sodium ion transport NAS 9828131
GO:0007399 nervous system development TAS 9828131
GO:0007411 axon guidance --
GO:0007422 peripheral nervous system development ISS --
genes like me logo Genes that share ontologies with SCN8A: view

Compounds for SCN8A Gene

(5) Tocris Compounds for SCN8A Gene

Compound Action Cas Number
Phrixotoxin 3 Potent modulator of NaV1.2, NaV1.3 and NaV1.5 channels [880886-00-0]
QX 314 chloride Na+ channel blocker [5369-03-9]
Tetrodotoxin Na+ channel blocker [4368-28-9]
Tetrodotoxin citrate Na+ channel blocker. Citrate salt of tetrodotoxin (Cat. No. 1078) [18660-81-6]
Veratridine Voltage-gated Na+ channel opener [71-62-5]

(1) HMDB Compounds for SCN8A Gene

Compound Synonyms Cas Number PubMed IDs
Sodium
  • Sodium
7440-23-5

(8) IUPHAR Ligand for SCN8A Gene

Ligand Type Action Affinity Pubmed IDs
tetrodotoxin Pore Blocker Antagonist 7.6
AFT-II Gating inhibitor Antagonist 7.5
ATX-II Gating inhibitor Antagonist 7.3
Bc-III Gating inhibitor Antagonist 6.1
beta-scorpion toxin Cn2 Activator None
veratridine Activator None
saxitoxin Channel blocker None
batrachotoxin Activator None

(2) Novoseek inferred chemical compound relationships for SCN8A Gene

Compound -log(P) Hits PubMed IDs
sodium 70.5 25
potassium 22.4 1
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) (6.8), Brain - Cerebellar Hemisphere (6.2), Brain - Cerebellum (4.9), and Brain - Anterior cingulate cortex (BA24) (4.9).

Integrated Proteomics: protein expression 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 expressions with SCN8A: view

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
chimpanzee
(Pan troglodytes)
Mammalia SCN8A 35
  • 99.21 (n)
  • 99.53 (a)
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
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 59 (a)
OneToMany
-- 36
  • 92 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Scn8a 35
  • 90.71 (n)
  • 98.69 (a)
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
scn8aa 36
  • 84 (a)
OneToMany
scn8ab 35
  • 75.98 (n)
  • 84.28 (a)
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 MAF
rs3562 -- 51,811,270(-) CTTTT(C/T)TTCCA utr-variant-3-prime
rs60637 Likely benign 51,806,958(+) AAGCC(A/C/G/T)AATAC synonymous-codon, reference
rs167337 -- 51,788,268(-) GGGGT(C/T)GGAAA intron-variant
rs172559 -- 51,810,462(+) GGCAA(C/T)GCTTT utr-variant-3-prime
rs215751 -- 51,752,184(-) TCACA(A/G)CTACT intron-variant

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

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

(2) OMIM Diseases for SCN8A Gene (600702)

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.

(2) Novoseek inferred disease relationships for SCN8A Gene

Disease -log(P) Hits PubMed IDs
neurological disorders 42.4 3
paralysis 41.5 2

Relevant External Links for SCN8A

Genetic Association Database (GAD)
SCN8A
Human Genome Epidemiology (HuGE) Navigator
SCN8A
genes like me logo Genes that share disorders with SCN8A: view

Publications for SCN8A Gene

  1. 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
  2. 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 48
  3. 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 4 23
  4. 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
  5. Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells. (PMID: 9295353) Plummer N.W. … Meisler M.H. (J. Biol. Chem. 1997) 3 4

Products for SCN8A Gene

Sources for SCN8A Gene

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