CHRNB4

Chr 15

cholinergic receptor nicotinic beta 4 subunit

NCBI Gene: 1143 ENSG00000117971 UniProt: P30926 OMIM: 118509

This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CHRNB4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.143

Z-score 2.95

OE 0.27 (0.14–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.20Z-score

OE missense 0.81 (0.73–0.90)

257 obs / 316.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.14–0.56)

0≤0.351.4

Missense OE?0.81 (0.73–0.90)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 5 / 18.8Missense obs/exp: 257 / 316.9Syn Z: -1.01

Background carrier burden — how many people carry a rare variant somewhere in CHRNB4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

720 rare PASS variants

Rare truncating (LoF)

1 in 1,100

98 rare PASS variants

Rare synonymous (reference)

1 in 140

309 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRNB4. 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 110	1 in 1,100
South Asian	~43k	1 in 75	1 in 2,900
Remaining (unassigned)	~30k	1 in 62	1 in 840
European (Finnish)	~27k	1 in 190	1 in 3,200
Admixed American	~22k	1 in 58	1 in 1,200
African / African American	~21k	1 in 48	1 in 1,100
East Asian	~20k	1 in 47	1 in 590
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 55	≈ 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.

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