Human Gene SCN8A (ENST00000354534.11) from GENCODE V44
  Description: Homo sapiens sodium voltage-gated channel alpha subunit 8 (SCN8A), transcript variant 1, mRNA. (from RefSeq NM_014191)
RefSeq Summary (NM_014191): 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].
Gencode Transcript: ENST00000354534.11
Gencode Gene: ENSG00000196876.19
Transcript (Including UTRs)
   Position: hg38 chr12:51,591,233-51,812,864 Size: 221,632 Total Exon Count: 27 Strand: +
Coding Region
   Position: hg38 chr12:51,662,818-51,807,429 Size: 144,612 Coding Exon Count: 26 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:51,591,233-51,812,864)mRNA (may differ from genome)Protein (1980 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: SCN8A_HUMAN
DESCRIPTION: RecName: Full=Sodium channel protein type 8 subunit alpha; AltName: Full=Sodium channel protein type VIII subunit alpha; AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.6;
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.
SUBUNIT: Interacts with NEDD4 and NEDD4L (By similarity). Interacts with FGF13; may regulate SCN8A activity.
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
SUBCELLULAR LOCATION: Isoform 5: Cytoplasmic vesicle. Note=Some vesicles are localized adjacent to melanoma invadopodia and macrophage podosomes. Does not localize to the plasma membrane.
TISSUE SPECIFICITY: Isoform 5 is expressed in non-neuronal tissues, such as monocytes/macrophages.
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.
PTM: May be ubiquitinated by NEDD4L; which would promote its endocytosis (By similarity).
DISEASE: Defects in SCN8A are the cause of 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.
DISEASE: Defects in SCN8A are the cause of epileptic encephalopathy, early infantile, type 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.
SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.
SIMILARITY: Contains 1 IQ domain.

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SCN8A
Diseases sorted by gene-association score: epileptic encephalopathy, early infantile, 13* (1332), seizures, benign familial infantile, 5* (1230), cognitive impairment with or without cerebellar ataxia* (969), scn8a encephalopathy* (418), scn8a-related epilepsy with encephalopathy* (400), undetermined early-onset epileptic encephalopathy* (350), convulsions, familial infantile, with paroxysmal choreoathetosis* (247), benign familial infantile epilepsy* (216), myoclonic epilepsy of infancy (10), breast angiosarcoma (9), pulpitis (8), generalized epilepsy with febrile seizures plus (7), amblyopia (7), breast sarcoma (7), west syndrome (5), myotonia (5), epileptic encephalopathy, early infantile, 6 (4), intellectual disability (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 4.25 RPKM in Brain - Cerebellum
Total median expression: 24.40 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -66.90181-0.370 Picture PostScript Text
3' UTR -1641.405435-0.302 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR024583 - DUF3451
IPR005821 - Ion_trans_dom
IPR000048 - IQ_motif_EF-hand-BS
IPR008054 - Na_channel_a8su
IPR001696 - Na_channel_asu
IPR010526 - Na_trans_assoc

Pfam Domains:
PF11933 - Cytoplasmic domain of voltage-gated Na+ ion channel
PF00520 - Ion transport protein
PF00612 - IQ calmodulin-binding motif
PF06512 - Sodium ion transport-associated

ModBase Predicted Comparative 3D Structure on Q9UQD0
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005216 ion channel activity
GO:0005244 voltage-gated ion channel activity
GO:0005248 voltage-gated sodium channel activity
GO:0005272 sodium channel activity
GO:0005515 protein binding
GO:0005524 ATP binding

Biological Process:
GO:0006811 ion transport
GO:0006814 sodium ion transport
GO:0007399 nervous system development
GO:0007422 peripheral nervous system development
GO:0019228 neuronal action potential
GO:0034220 ion transmembrane transport
GO:0034765 regulation of ion transmembrane transport
GO:0035725 sodium ion transmembrane transport
GO:0042552 myelination
GO:0055085 transmembrane transport
GO:0086010 membrane depolarization during action potential

Cellular Component:
GO:0001518 voltage-gated sodium channel complex
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030018 Z disc
GO:0031410 cytoplasmic vesicle
GO:0033268 node of Ranvier
GO:0043194 axon initial segment


-  Descriptions from all associated GenBank mRNAs
  AY510083 - Homo sapiens clone n1a voltage-gated sodium channel type VIII alpha protein (SCN8A) mRNA, partial cds.
AK309213 - Homo sapiens cDNA, FLJ99254.
AY510076 - Homo sapiens clone n1b voltage-gated sodium channel type VIII alpha protein (SCN8A) mRNA, partial cds.
AB027567 - Homo sapiens SCN8A mRNA for sodium channel, complete cds.
FJ611941 - Homo sapiens monocyte-macrophage NaV1.6 splice variant (SCN8A) mRNA, complete cds, alternatively spliced.
AF225988 - Homo sapiens voltage-gated sodium channel alpha subunit (SCN8A) mRNA, complete cds.
BC172876 - Synthetic construct Homo sapiens clone IMAGE:9094452 sodium channel, voltage gated, type VIII, alpha (SCN8A) gene, partial cds.
JD056608 - Sequence 37632 from Patent EP1572962.
DQ581161 - Homo sapiens piRNA piR-49273, complete sequence.
AY682081 - Homo sapiens voltage-gated sodium channel Nav1.6 (SCN8A) mRNA, partial cds, alternatively spliced.
AY682082 - Homo sapiens voltage-gated sodium channel Nav1.6 (SCN8A) mRNA, partial cds, alternatively spliced.
AY682083 - Homo sapiens voltage-gated sodium channel Nav1.6 (SCN8A) mRNA, partial cds, alternatively spliced.
BC172906 - Synthetic construct Homo sapiens clone IMAGE:9094482 sodium channel, voltage gated, type VIII, alpha (SCN8A) gene, partial cds.
Z50169 - H. sapiens partial mRNA; single read (clone A33292).
AJ276141 - Homo sapiens partial mRNA for hNa6/Scn8a voltage-gated sodium channel (SCN8A gene), cell line PC-3.
AJ276142 - Homo sapiens partial mRNA for hNa6/Scn8a voltage-gated sodium channel (SCN8A gene), cell line LNCaP.
AJ277395 - Homo sapiens partial mRNA for voltage-gated sodium channel (SCN8A gene).
AJ310884 - Homo sapiens mRNA for Nav1.6 voltage-gated sodium channel (SCN8A gene) Nav1.6, D3 neonatal splice variant, cell lines MDA-MB-231.
AJ310885 - Homo sapiens partial mRNA for voltage-gated sodium channel Nav1.6 (SCN8A gene), D3 neonatal splice variant, cell line MCF-7.
AJ310898 - Homo sapiens partial mRNA for voltage-gated sodium channel Nav1.6 (SCN8A gene), cell line MCF-7.
JD114304 - Sequence 95328 from Patent EP1572962.
JD312474 - Sequence 293498 from Patent EP1572962.
JD254553 - Sequence 235577 from Patent EP1572962.
JD350867 - Sequence 331891 from Patent EP1572962.
JD318802 - Sequence 299826 from Patent EP1572962.
JD503371 - Sequence 484395 from Patent EP1572962.
JD102590 - Sequence 83614 from Patent EP1572962.
JD500620 - Sequence 481644 from Patent EP1572962.
JD038598 - Sequence 19622 from Patent EP1572962.
JD310521 - Sequence 291545 from Patent EP1572962.
JD467949 - Sequence 448973 from Patent EP1572962.
JD162799 - Sequence 143823 from Patent EP1572962.
JD303328 - Sequence 284352 from Patent EP1572962.
JD556555 - Sequence 537579 from Patent EP1572962.
JD556556 - Sequence 537580 from Patent EP1572962.
JD368152 - Sequence 349176 from Patent EP1572962.
AK091315 - Homo sapiens cDNA FLJ33996 fis, clone DFNES2008881.
AX746911 - Sequence 436 from Patent EP1308459.
JD488502 - Sequence 469526 from Patent EP1572962.
JD197278 - Sequence 178302 from Patent EP1572962.
JD301067 - Sequence 282091 from Patent EP1572962.
JD279693 - Sequence 260717 from Patent EP1572962.
JD284435 - Sequence 265459 from Patent EP1572962.
JD562228 - Sequence 543252 from Patent EP1572962.
JD380047 - Sequence 361071 from Patent EP1572962.
JD348941 - Sequence 329965 from Patent EP1572962.
JD196796 - Sequence 177820 from Patent EP1572962.
JD087956 - Sequence 68980 from Patent EP1572962.
JD265051 - Sequence 246075 from Patent EP1572962.
JD071725 - Sequence 52749 from Patent EP1572962.
JD386898 - Sequence 367922 from Patent EP1572962.
JD278674 - Sequence 259698 from Patent EP1572962.
JD459566 - Sequence 440590 from Patent EP1572962.
JD548025 - Sequence 529049 from Patent EP1572962.
JD492757 - Sequence 473781 from Patent EP1572962.
JD253955 - Sequence 234979 from Patent EP1572962.
JD397662 - Sequence 378686 from Patent EP1572962.
JD248755 - Sequence 229779 from Patent EP1572962.
JD400232 - Sequence 381256 from Patent EP1572962.
JD255694 - Sequence 236718 from Patent EP1572962.
JD454856 - Sequence 435880 from Patent EP1572962.
JD238772 - Sequence 219796 from Patent EP1572962.
JD172361 - Sequence 153385 from Patent EP1572962.
JD442040 - Sequence 423064 from Patent EP1572962.
JD268790 - Sequence 249814 from Patent EP1572962.
JD331397 - Sequence 312421 from Patent EP1572962.
JD114034 - Sequence 95058 from Patent EP1572962.
JD361212 - Sequence 342236 from Patent EP1572962.
JD073030 - Sequence 54054 from Patent EP1572962.
JD384955 - Sequence 365979 from Patent EP1572962.
JD162434 - Sequence 143458 from Patent EP1572962.
JD162433 - Sequence 143457 from Patent EP1572962.
JD375788 - Sequence 356812 from Patent EP1572962.
JD419426 - Sequence 400450 from Patent EP1572962.
JD411628 - Sequence 392652 from Patent EP1572962.
JD300625 - Sequence 281649 from Patent EP1572962.
JD039033 - Sequence 20057 from Patent EP1572962.
JD068802 - Sequence 49826 from Patent EP1572962.
JD314313 - Sequence 295337 from Patent EP1572962.
JD430811 - Sequence 411835 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9UQD0 (Reactome details) participates in the following event(s):

R-HSA-373739 Ankyrins link voltage-gated sodium and potassium channels to spectrin and L1
R-HSA-5576895 SCNAs:SNCBs transport Na+ from extracellular region to cytosol
R-HSA-445095 Interaction between L1 and Ankyrins
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-373760 L1CAM interactions
R-HSA-5576891 Cardiac conduction
R-HSA-422475 Axon guidance
R-HSA-397014 Muscle contraction
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B9VWG8, ENST00000354534.1, ENST00000354534.10, ENST00000354534.2, ENST00000354534.3, ENST00000354534.4, ENST00000354534.5, ENST00000354534.6, ENST00000354534.7, ENST00000354534.8, ENST00000354534.9, MED, NM_014191, O95788, Q9NYX2, Q9UPB2, Q9UQD0, SCN8A_HUMAN, uc001ryw.1, uc001ryw.2, uc001ryw.3, uc001ryw.4, uc001ryw.5
UCSC ID: ENST00000354534.11
RefSeq Accession: NM_014191
Protein: Q9UQD0 (aka SCN8A_HUMAN or CIN8_HUMAN)
CCDS: CCDS44891.1, CCDS53794.1, CCDS81692.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SCN8A:
scn8a-ee (SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.