SCN11A
Chr 3ADsodium voltage-gated channel alpha subunit 11
Also known as: FEPS3, HSAN7, NAV1.9, NaN, PN5, SCN12A, SNS-2
The protein forms voltage-gated sodium channels that mediate sodium ion permeability in excitable membranes and is highly expressed in nociceptive neurons where it transmits pain signals from the periphery to the central nervous system. Mutations cause familial episodic pain syndrome-3 and hereditary sensory and autonomic neuropathy type VII with autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants (very low pLI score), suggesting the associated phenotypes may involve other mutational mechanisms.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. 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
500 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 | 3 | 0 | 3 |
Likely Pathogenic | 0 | 1 | 0 | 0 | 1 |
VUS | 34 | 271 | 17 | 8 | 330 |
Likely Benign | 1 | 18 | 45 | 80 | 144 |
Benign | 0 | 0 | 3 | 1 | 4 |
Conflicting | — | 12 | |||
| Total | 35 | 290 | 68 | 89 | 494 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCN11A · 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