CHRNB2

Chr 1AD

cholinergic receptor nicotinic beta 2 subunit

Also known as: EFNL3, nAChRB2

NCBI Gene: 1141 ENSG00000160716 UniProt: P17787 OMIM: 118507

This protein forms the beta-2 subunit of pentameric neuronal acetylcholine receptors, which are ligand-gated cation channels with high calcium permeability that mediate excitatory synaptic transmission in the nervous system. Mutations cause autosomal dominant nocturnal frontal lobe epilepsy, a form of epilepsy characterized by seizures that occur predominantly during sleep. The gene shows tolerance to loss-of-function variants (pLI 0.0007), suggesting the pathogenic variants likely affect receptor function through other mechanisms.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, nocturnal frontal lobe, 3MIM #605375

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · familial sleep-related hypermotor epilepsy · AD · ClinGen 2023

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

GOF*

Mechanism· G2P

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GeneReview available — CHRNB2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in CHRNB2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

644 rare PASS variants

Rare truncating (LoF)

1 in 890

98 rare PASS variants

Rare synonymous (reference)

1 in 130

341 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRNB2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 2,600
South Asian	~43k	1 in 120	1 in 2,000
Remaining (unassigned)	~30k	1 in 110	1 in 2,100
European (Finnish)	~27k	1 in 250	1 in 4,300
Admixed American	~22k	1 in 120	1 in 1,800
African / African American	~21k	1 in 130	1 in 2,000
East Asian	~20k	1 in 120	1 in 2,400
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓