SCN10A Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the SCN10A gene, encoding the voltage-gated sodium channel Nav1.8, its role in pain and cardiac electrophysiology, associated diseases, expression patterns, and mutation spectrum.
Gene Information Card
| Symbol | SCN10A |
|---|---|
| Full Name | sodium voltage-gated channel alpha subunit 10 |
| Gene Type | protein coding |
| Chromosomal Location | 3p22.2 |
| NCBI Gene ID | 6336 ncbi.nlm.nih.gov/gene/6336 |
| Ensembl ID | ENSG00000185313 |
| UniProt ID | Q9Y5Y9 |
| OMIM ID | 604427 |
| HGNC ID | 10582 |
| Aliases | Nav1.8, PN5, SNS, hPN5 |
Description
The SCN10A gene encodes the alpha subunit of the voltage-gated sodium channel Nav1.8. This channel is primarily expressed in sensory neurons of the dorsal root ganglia and trigeminal ganglia, where it plays a critical role in nociception and pain signaling. Additionally, SCN10A is expressed in cardiac tissue, particularly in intracardiac neurons and to a lesser extent in cardiomyocytes, where it influences cardiac conduction and arrhythmia susceptibility. Mutations in SCN10A have been associated with various pain disorders, cardiac arrhythmias, and neuropathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brugada syndrome | Gain-of-function mutations increase sodium current, leading to altered cardiac repolarization and arrhythmia risk. | ClinVar, OMIM |
| Small fiber neuropathy | Loss-of-function mutations reduce pain signaling, contributing to neuropathic pain symptoms. | ClinVar, OMIM |
| Erythromelalgia | Gain-of-function mutations enhance neuronal excitability, causing burning pain and redness. | ClinVar, OMIM |
| Paroxysmal extreme pain disorder | Gain-of-function mutations cause hyperexcitability of sensory neurons, leading to severe pain episodes. | ClinVar, OMIM |
| Atrial fibrillation | Variants in SCN10A may alter cardiac sodium current, increasing susceptibility to atrial fibrillation. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Dorsal root ganglia | High | Predominant expression in nociceptive neurons |
| Trigeminal ganglia | High | Pain-sensing neurons |
| Heart | Low | Intracardiac neurons and some cardiomyocytes |
| Nerve | Medium | Peripheral nerves |
| Skin | Low | Nerve endings |
| Brain | Low | Minimal expression |
| Liver | Not detected | No significant expression |
| Kidney | Not detected | No significant expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| DRG neurons | High | Key nociceptors |
| Cardiomyocytes | Low | Minor expression |
| Intracardiac neurons | High | Regulate cardiac function |
| HEK293 (transfected) | High | Used for functional studies |
| SH-SY5Y | Low | Neuroblastoma cell line |
| Caco-2 | Not detected | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg856Cys | Missense | Rare | Gain-of-function; associated with erythromelalgia |
| p.Val1316Ala | Missense | Rare | Gain-of-function; associated with paroxysmal extreme pain disorder |
| p.Arg1268Gln | Missense | Rare | Loss-of-function; associated with small fiber neuropathy |
| p.Gly1662Ser | Missense | Rare | Gain-of-function; associated with Brugada syndrome |
| p.Leu954Phe | Missense | Rare | Gain-of-function; associated with atrial fibrillation |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations reduce sodium current, leading to decreased neuronal excitability and impaired pain signaling, as seen in small fiber neuropathy.
Gain of Function (GOF)
Gain-of-function mutations increase sodium current, causing hyperexcitability of sensory neurons and cardiac myocytes, contributing to pain disorders and arrhythmias.
Dominant Negative (DN)
No clear dominant-negative effects have been reported for SCN10A mutations; most act via gain- or loss-of-function mechanisms.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated sodium channel activity | • sodium ion binding |
| • ion channel activity | • plasma membrane |
| • integral component of plasma membrane | • response to pain |
| • action potential propagation | • sodium ion transport |
| • regulation of cardiac conduction |
Pathways
• Voltage-gated sodium channel pathway
• Pain signaling pathway
• Cardiac conduction pathway
• Nociception pathway
Protein Summary
The Nav1.8 protein is a 1956-amino acid alpha subunit that forms a functional sodium channel when associated with beta subunits. It is characterized by four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The channel is tetrodotoxin-resistant and plays a crucial role in the rising phase of action potentials in nociceptive neurons. In the heart, Nav1.8 contributes to late sodium current and influences cardiac excitability. Post-translational modifications, such as phosphorylation, modulate channel activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCN10A Overexpression HEK293T Stable Cell Line | EDC01586 | Human | 6336 | Details Get a Quote |
| SCN10A Knockout HEK293 Cell Line | EDJ-KQ4977 | Human | 6336 | Details Get a Quote |
| SCN10A Knockout HeLa Cell Line | EDJ-KQ54406 | Human | 6336 | Details Get a Quote |
| SCN10A Knockout A-549 Cell Line | EDJ-KQ62896 | Human | 6336 | Details Get a Quote |
| SCN10A Knockout HCT 116 Cell Line | EDJ-KQ71362 | Human | 6336 | Details Get a Quote |
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