KCNQ3
Chr 8ADpotassium voltage-gated channel subfamily Q member 3
Also known as: BFNC2, EBN2, KV7.3
The protein forms M-channels by associating with KCNQ2 or KCNQ5 to regulate neuronal excitability, with these channels being inhibited by muscarinic acetylcholine receptors and activated by retigabine. Mutations cause benign familial neonatal convulsions type 2 through an autosomal dominant inheritance pattern. The pathogenic mechanism involves gain-of-function mutations that alter normal channel function.
Definitive — sufficient evidence for diagnostic panels
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
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 | 6 | 3 | 15 | 0 | 24 |
Likely Pathogenic | 4 | 10 | 1 | 0 | 15 |
VUS | 14 | 250 | 17 | 1 | 282 |
Likely Benign | 0 | 4 | 61 | 89 | 154 |
Benign | 0 | 0 | 3 | 0 | 3 |
Conflicting | — | 13 | |||
| Total | 24 | 267 | 97 | 90 | 491 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNQ3 · 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
External Resources
Links to major genomics databases and tools