CHRNB3

Chr 8

cholinergic receptor nicotinic beta 3 subunit

NCBI Gene: 1142 ENSG00000147432 UniProt: Q05901 OMIM: 118508

The CHRNB3 protein is a beta subunit component of neuronal nicotinic acetylcholine receptors, which are pentameric ligand-gated cation channels that mediate excitatory synaptic transmission in the nervous system. Mutations in CHRNB3 cause autosomal dominant nocturnal frontal lobe epilepsy, a focal epilepsy syndrome with seizures that typically occur during sleep and begin in childhood or adolescence. The gene shows low constraint against loss-of-function variants (pLI <0.001), suggesting that complete loss of function may be tolerated.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.[supplied by OMIM, Apr 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CHRNB3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.71

OE 0.58 (0.36–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.85 (0.76–0.95)

220 obs / 258.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.36–0.95)

0≤0.351.4

Missense OE?0.85 (0.76–0.95)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 11 / 19.1Missense obs/exp: 220 / 258.0Syn Z: 0.84

Background carrier burden — how many people carry a rare variant somewhere in CHRNB3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

547 rare PASS variants

Rare truncating (LoF)

1 in 650

100 rare PASS variants

Rare synonymous (reference)

1 in 360

224 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRNB3. 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 220	1 in 990
South Asian	~43k	1 in 79	1 in 1,300
Remaining (unassigned)	~30k	1 in 96	1 in 400
European (Finnish)	~27k	1 in 830	≈ 1 in 8,900
Admixed American	~22k	1 in 69	1 in 830
African / African American	~21k	1 in 96	1 in 550
East Asian	~20k	1 in 140	1 in 510
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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.