SCN10A
Chr 3ADsodium voltage-gated channel alpha subunit 10
Also known as: FEPS2, Nav1.8, PN3, SNS
Encodes a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit that mediates sodium ion permeability across excitable membranes and plays a role in neuropathic pain mechanisms. Mutations cause episodic pain syndrome, familial, type 2 with autosomal dominant inheritance. This gene is not constrained against loss-of-function variants (very low pLI score), suggesting complete loss of function may be tolerated.
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 1 | 0 | 1 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 18 | 143 | 3 | 2 | 166 |
Likely Benign | 0 | 3 | 41 | 45 | 89 |
Benign | 0 | 0 | 15 | 0 | 15 |
Conflicting | — | 29 | |||
| Total | 18 | 146 | 60 | 47 | 300 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCN10A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools