CHRNB1
Chr 17ARADcholinergic receptor nicotinic beta 1 subunit
Also known as: ACHRB, CHRNB, CMS1D, CMS2A, CMS2C, SCCMS
This gene encodes the beta subunit of the muscle acetylcholine receptor, which opens an ion channel across the postsynaptic membrane when acetylcholine binds. Mutations cause congenital myasthenic syndrome with either slow-channel kinetics (autosomal dominant, gain-of-function mechanism) or acetylcholine receptor deficiency (autosomal recessive). The dominant form results from prolonged channel opening, while the recessive form involves receptor deficiency.
Definitive — sufficient evidence for diagnostic panels
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 (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 | 4 | 0 | 12 | 0 | 16 |
Likely Pathogenic | 8 | 0 | 0 | 0 | 8 |
VUS | 5 | 148 | 11 | 4 | 168 |
Likely Benign | 0 | 1 | 42 | 50 | 93 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 4 | |||
| Total | 17 | 149 | 67 | 54 | 291 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CHRNB1 · 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