CHRNB2

Chr 1

cholinergic receptor nicotinic beta 2 subunit

Also known as: EFNL3, nAChRB2

NCBI Gene: 1141ENSG00000160716UniProt: P17787

Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Epilepsy, nocturnal frontal lobe, 3MIM #605375
515
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CHRNB2
🧬
Gene-Disease Validity (ClinGen)
sleep-related hypermotor epilepsy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 275 VUS of 515 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.
0.82LOEUF
pLI 0.001
Z-score 2.11
OE 0.46 (0.27–0.82)
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.
2.10Z-score
OE missense 0.67 (0.60–0.75)
221 obs / 328.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.46 (0.27–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.60–0.75)
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: 8 / 17.6Missense obs/exp: 221 / 328.2Syn Z: -0.20

ClinVar Variant Classifications

515 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic6
VUS275
Likely Benign183
Benign11
Conflicting26
14
Pathogenic
6
Likely Pathogenic
275
VUS
183
Likely Benign
11
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
12
0
14
Likely Pathogenic
1
3
2
0
6
VUS
18
220
30
7
275
Likely Benign
0
14
35
134
183
Benign
0
0
11
0
11
Conflicting
—26
Total1923990141515

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

View in ClinVar →

Protein Context — Lollipop Plot

CHRNB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CHRNB2-related nocturnal frontal lobe epilepsy

strong
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

Epilepsy, nocturnal frontal lobe, 3

MIM #605375

Molecular basis of disorder known

📖
GeneReview available — CHRNB2
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, molecular, physiologic, and therapeutic feature of patients with CHRNA4 and CHRNB2 deficiency: A systematic review.
Jalaiei A et al.·J Neurochem
2025Review
Rare coding variants in CHRNB2 reduce the likelihood of smoking.
Rajagopal VM et al.·Nat Genet
2023
The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype.
Csala I et al.·Prog Neuropsychopharmacol Biol Psychiatry
2015
Generalized epilepsy in a family with basal ganglia calcifications and mutations in SLC20A2 and CHRNB2.
Fjaer R et al.·Eur J Med Genet
2015Case report
Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.
Cadieux-Dion M et al.·Can J Neurol Sci
2020Cohort
Novel ADGRV1 pathogenic variant associated to sleep-related hypermotor epilepsy.
Russo A et al.·Epileptic Disord
2025Case report
Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay.
Wang S et al.·Psychiatr Genet
2023
Blockade of CHRNB2 signaling with a therapeutic monoclonal antibody attenuates the aggressiveness of gastric cancer cells.
Kanda M et al.·Oncogene
2021
The role of the nicotinic acetylcholine receptors in sleep-related epilepsy.
Marini C et al.·Biochem Pharmacol
2007Review
Autosomal dominant nocturnal frontal lobe epilepsy--a critical overview.
Combi R et al.·J Neurol
2004Review
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