CHRNA3

Chr 15AR

cholinergic receptor nicotinic alpha 3 subunit

Also known as: BAIPRCK, LNCR2, NACHRA3, PAOD2

NCBI Gene: 1136 ENSG00000080644 UniProt: P32297 OMIM: 118503

This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Lung cancer susceptibility 2}MIM #612052

Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUTMIM #191800

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.09

OE 0.72 (0.47–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.73Z-score

OE missense 0.88 (0.79–0.97)

247 obs / 281.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.47–1.15)

0≤0.351.4

Missense OE?0.88 (0.79–0.97)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 13 / 18.0Missense obs/exp: 247 / 281.7Syn Z: -2.55

Background carrier burden — how many people carry a rare variant somewhere in CHRNA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

604 rare PASS variants

Rare truncating (LoF)

1 in 560

140 rare PASS variants

Rare synonymous (reference)

1 in 150

309 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRNA3. 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 170	1 in 590
South Asian	~43k	1 in 86	1 in 530
Remaining (unassigned)	~30k	1 in 95	1 in 600
European (Finnish)	~27k	1 in 260	1 in 5,300
Admixed American	~22k	1 in 110	1 in 780
African / African American	~21k	1 in 110	1 in 580
East Asian	~20k	1 in 120	1 in 340
Ashkenazi Jewish	~13k	1 in 300	1 in 930
Middle Eastern	~2,884	1 in 100	1 in 580

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓