CHRNA5

Chr 15

cholinergic receptor nicotinic alpha 5 subunit

Also known as: LNCR2

NCBI Gene: 1138 ENSG00000169684 UniProt: P30532

The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.16

OE 0.69 (0.43–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.07Z-score

OE missense 0.81 (0.72–0.91)

197 obs / 244.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.43–1.14)

0≤0.351.4

Missense OE?0.81 (0.72–0.91)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 11 / 16.0Missense obs/exp: 197 / 244.2Syn Z: 0.93

Background carrier burden — how many people carry a rare variant somewhere in CHRNA5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

510 rare PASS variants

Rare truncating (LoF)

1 in 460

118 rare PASS variants

Rare synonymous (reference)

1 in 180

194 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CHRNA5; this gene does not show strong loss-of-function constraint by this measure. 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 480
South Asian	~43k	1 in 75	1 in 590
Remaining (unassigned)	~30k	1 in 90	1 in 300
European (Finnish)	~27k	1 in 310	≈ 1 in 6,700
Admixed American	~22k	1 in 130	1 in 550
African / African American	~21k	1 in 63	1 in 600
East Asian	~20k	1 in 120	1 in 380
Ashkenazi Jewish	~13k	1 in 280	1 in 1,800
Middle Eastern	~2,884	1 in 100	1 in 480

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): 3 of 6 coding exons well covered in gnomAD exomes; exons 1, 3, 4 marginal. Genomes: all 6.? see exons ↓