CHRNB1

Chr 17ARAD

cholinergic receptor nicotinic beta 1 subunit

NCBI Gene: 1140ENSG00000170175UniProt: P11230

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane

Primary Disease Associations & Inheritance

?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiencyMIM #616314
AR
Myasthenic syndrome, congenital, 2A, slow-channelMIM #616313
AD
590
ClinVar variants
51
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CHRNB1
🧬
Gene-Disease Validity (ClinGen)
congenital myasthenic syndrome 2C · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 304 VUS of 590 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.00LOEUF
pLI 0.000
Z-score 1.58
OE 0.65 (0.43–1.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.44Z-score
OE missense 0.93 (0.84–1.03)
266 obs / 286.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.43–1.00)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.84–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 15 / 23.2Missense obs/exp: 266 / 286.9Syn Z: -0.19

ClinVar Variant Classifications

590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic21
VUS304
Likely Benign164
Benign42
Conflicting29
30
Pathogenic
21
Likely Pathogenic
304
VUS
164
Likely Benign
42
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
22
0
30
Likely Pathogenic
12
2
7
0
21
VUS
5
244
49
6
304
Likely Benign
0
1
73
90
164
Benign
0
0
42
0
42
Conflicting
—29
Total2424819396590

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.

Gene2Phenotype Curations

CHRNB1-related congenital myaesthenia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

CHRNB1-related congenital myaesthenia

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency

MIM #616314

Molecular basis of disorder known

Autosomal recessive

Myasthenic syndrome, congenital, 2A, slow-channel

MIM #616313

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — CHRNB1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
Neurogenetic fetal akinesia and arthrogryposis: genetics, expanding genotype-phenotypes and functional genomics.
Ravenscroft G et al.·J Med Genet
2021Functional
Causal Variants in CHRNA1 and CHRNB1 Genes for Anti-acetylcholine Receptor Antibody Positive Myasthenia Gravis: Evidence from Bayesian Fine-Mapping and Genetic Association Study.
Garai N et al.·Mol Neurobiol
2025
Congenital Myasthenic Syndromes in Belgium: Genetic and Clinical Characterization of Pediatric and Adult Patients.
Smeets N et al.·Pediatr Neurol
2024Cohort
Whole-exome sequencing reveals sex difference in the genetic architecture of high myopia.
Liu X et al.·J Med Genet
2025
Clinical and genetic features of congenital myasthenic syndrome due to the muscle acetylcholine receptor genes.
Guan J et al.·Brain Dev
2025
Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients.
Vogt J et al.·Am J Hum Genet
2008Cohort
CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum.
Freed AS et al.·Am J Med Genet A
2021Case report
Monoamine neurotransmitter-related gene-based genome-wide association study of low-dose ketamine in patients with treatment-resistant depression.
Kao CF et al.·J Psychopharmacol
2025Cohort
Congenital Myasthenic Syndromes in Turkey: Clinical and Molecular Characterization of 16 Cases With Three Novel Mutations.
Öztürk S et al.·Pediatr Neurol
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools