SCN8A Gene: Sodium Voltage-Gated Channel Alpha Subunit 8
A critical neuronal sodium channel gene implicated in epilepsy and neurodevelopmental disorders
Gene Information Card
| Symbol | SCN8A |
|---|---|
| Full Name | Sodium voltage-gated channel alpha subunit 8 |
| Gene Type | protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 6334 ncbi.nlm.nih.gov/gene/6334 |
| Ensembl ID | ENSG00000196876 |
| UniProt ID | Q9UQD0 |
| OMIM ID | 600702 |
| HGNC ID | 10596 |
| Aliases | Nav1.6, PN4, CER1, EIEE13, BFIS5, MED13 |
Description
The SCN8A gene encodes the alpha subunit of the voltage-gated sodium channel Nav1.6, which is primarily expressed in neurons. This channel is critical for the initiation and propagation of action potentials, particularly at the axon initial segment and nodes of Ranvier. Mutations in SCN8A are associated with a spectrum of neurological disorders, including early infantile epileptic encephalopathy type 13 (EIEE13), benign familial infantile seizures 5 (BFIS5), and cognitive impairment with or without cerebellar ataxia. The gene is highly conserved across species and plays a pivotal role in neuronal excitability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy 13 (DEE13) | Gain-of-function mutations increase channel activity, leading to neuronal hyperexcitability and seizures. | ClinVar, OMIM |
| Benign familial infantile seizures 5 (BFIS5) | Missense mutations may alter channel gating, causing transient hyperexcitability in infancy. | ClinVar, OMIM |
| Cognitive impairment with or without cerebellar ataxia | Loss-of-function mutations reduce channel expression or function, impairing neuronal signaling. | ClinVar, OMIM |
| Episodic ataxia | Rare mutations affecting channel kinetics may disrupt cerebellar function. | ClinVar, OMIM |
| Autism spectrum disorder | Rare variants may contribute to altered neuronal excitability and synaptic function. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.4 | High |
| Cerebellum | 28.9 | High |
| Cerebral cortex | 32.1 | High |
| Spinal cord | 18.2 | Medium |
| Testis | 4.3 | Low |
| Heart | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 25.6 | High expression |
| SK-N-AS (neuroblastoma) | 22.3 | High expression |
| U-87 MG (glioblastoma) | 15.4 | Medium expression |
| HEK 293 (embryonic kidney) | 0.8 | Low expression |
| Hep G2 (hepatocellular carcinoma) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asn1768Asp (N1768D) | Missense | Rare (de novo) | Gain-of-function; associated with DEE13 |
| p.Arg1872Gln (R1872Q) | Missense | Rare (de novo) | Gain-of-function; associated with DEE13 |
| p.Val1592Leu (V1592L) | Missense | Rare (de novo) | Gain-of-function; associated with DEE13 |
| p.Arg1617Gln (R1617Q) | Missense | Rare (de novo) | Gain-of-function; associated with DEE13 |
| p.Gly1451Ser (G1451S) | Missense | Rare (de novo) | Loss-of-function; associated with cognitive impairment |
| p.Arg1625His (R1625H) | Missense | Rare (de novo) | Gain-of-function; associated with BFIS5 |
Mutation functional classification
Loss of Function (LOF)
Reduced channel expression or function, leading to decreased neuronal excitability. Associated with cognitive impairment and ataxia.
Gain of Function (GOF)
Increased channel activity, causing neuronal hyperexcitability and seizures. Common in DEE13 and BFIS5.
Dominant Negative (DN)
Not well established for SCN8A; most pathogenic mutations are gain- or loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated sodium channel activity | • sodium ion binding |
| • ion channel activity | • plasma membrane |
| • axon initial segment | • node of Ranvier |
| • neuronal action potential | • sodium ion transmembrane transport |
Pathways
• Voltage-gated sodium channel complex
• Action potential propagation
• Ion transport
• Neuronal system
Protein Summary
The Nav1.6 protein is a large, pore-forming alpha subunit that forms a functional sodium channel when associated with auxiliary beta subunits. It is composed of four homologous domains (I-IV), each with six transmembrane segments (S1-S6). The S4 segments serve as voltage sensors, and the loop between domains III and IV forms the inactivation gate. Nav1.6 is highly enriched at the axon initial segment and nodes of Ranvier, where it mediates the rapid depolarization phase of action potentials. Its biophysical properties include fast activation and inactivation kinetics, and a significant resurgent current that contributes to repetitive firing. Post-translational modifications, such as phosphorylation, modulate channel activity and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCN8A Knockout HEK293 Cell Line | EDJ-KQ5720 | Human | 6334 | Details Get a Quote |
| SCN8A Knockout A-549 Cell Line | EDJ-KQ29107 | Human | 6334 | Details Get a Quote |
| SCN8A Knockout HCT 116 Cell Line | EDJ-KQ29108 | Human | 6334 | Details Get a Quote |
| SCN8A Knockout HeLa Cell Line | EDJ-KQ54405 | Human | 6334 | Details Get a Quote |
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