CHRNB3
Chr 8cholinergic receptor nicotinic beta 3 subunit
The CHRNB3 protein is a beta subunit component of neuronal nicotinic acetylcholine receptors, which are pentameric ligand-gated cation channels that mediate excitatory synaptic transmission in the nervous system. Mutations in CHRNB3 cause autosomal dominant nocturnal frontal lobe epilepsy, a focal epilepsy syndrome with seizures that typically occur during sleep and begin in childhood or adolescence. The gene shows low constraint against loss-of-function variants (pLI <0.001), suggesting that complete loss of function may be tolerated.
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). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CHRNB3 · 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