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
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.
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.
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.
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