CHRNB1

Chr 17

cholinergic receptor nicotinic beta 1 subunit

Also known as: ACHRB, CHRNB, CMS1D, CMS2A, CMS2C, SCCMS

NCBI Gene: 1140 ENSG00000170175 UniProt: P11230

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The muscle acetylcholine receptor is composed of five subunits: two alpha subunits and one beta, one gamma, and one delta subunit. This gene encodes the beta subunit of the acetylcholine receptor. The acetylcholine receptor changes conformation upon acetylcholine binding leading to the opening of an ion-conducting channel across the plasma membrane. Mutations in this gene are associated with slow-channel congenital myasthenic syndrome. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.00

Clinical Summary— CHRNB1

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Gene-Disease Validity (ClinGen)

congenital myasthenic syndrome 2C · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

36 unique Pathogenic / Likely Pathogenic· 306 VUS of 601 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CHRNB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.000

Z-score 1.58

OE 0.65 (0.43–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.44Z-score

OE missense 0.93 (0.84–1.03)

266 obs / 286.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.43–1.00)

0≤0.351.4

Missense OE?0.93 (0.84–1.03)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 15 / 23.2Missense obs/exp: 266 / 286.9Syn Z: -0.19

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCHRNB1-related congenital myaestheniaLOFAR

definitiveCHRNB1-related congenital myaestheniaGOFAD

This gene — mechanism propensity

0.80top 10%

GOF

0.83top 10%

LOF

0.1896th %ile

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.

GOFprediction above median · 1 literature citation

DNprediction above median

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

GOFThe pronounced abnormalities in neuromuscular synaptic architecture and function, muscle fiber damage and weakness, resulting from a single point mutation are a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 8651643 ↗

ClinVar Variant Classifications

601 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic19

VUS306

Likely Benign168

Benign50

Conflicting32

Pathogenic

Likely Pathogenic

306

VUS

168

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	4	3	0	17
Likely Pathogenic	16	2	1	0	19
VUS	8	256	36	6	306
Likely Benign	0	1	76	91	168
Benign	0	2	48	0	50
Conflicting	—				32
Total	34	265	164	97	592

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap CHRNB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →