SCN3B
Chr 11ADsodium voltage-gated channel beta subunit 3
Also known as: ATFB16, BRGDA7, HSA243396, SCNB3
The SCN3B gene encodes a beta subunit of voltage-gated sodium channels that regulates the inactivation kinetics of sodium channels responsible for action potential generation and propagation in neurons and muscle. Mutations cause autosomal dominant Brugada syndrome 7 and familial atrial fibrillation through a gain-of-function mechanism. The protein localizes to the cell membrane where it modulates sodium channel function.
Primary Disease Associations & Inheritance
Refuted — evidence has disproved this relationship
2 total gene-disease associations curated
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 (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. 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
327 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 | 2 | 50 | 0 | 52 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 10 | 101 | 20 | 1 | 132 |
Likely Benign | 0 | 1 | 33 | 60 | 94 |
Benign | 0 | 0 | 25 | 3 | 28 |
Conflicting | — | 12 | |||
| Total | 10 | 104 | 130 | 64 | 320 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCN3B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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