CHRM5

Chr 15

cholinergic receptor muscarinic 5

Also known as: HM5

NCBI Gene: 1133 ENSG00000184984 UniProt: P08912 OMIM: 118496

The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.004

Z-score 2.36

OE 0.40 (0.22–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.20Z-score

OE missense 0.80 (0.72–0.89)

235 obs / 293.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.22–0.74)

0≤0.351.4

Missense OE?0.80 (0.72–0.89)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 7 / 17.7Missense obs/exp: 235 / 293.0Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in CHRM5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 94

557 rare PASS variants

Rare truncating (LoF)

1 in 4,400

49 rare PASS variants

Rare synonymous (reference)

1 in 230

256 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRM5. 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 100	1 in 5,000
South Asian	~43k	1 in 85	1 in 3,600
Remaining (unassigned)	~30k	1 in 71	1 in 3,800
European (Finnish)	~27k	1 in 140	1 in 5,300
Admixed American	~22k	1 in 84	1 in 1,100
African / African American	~21k	1 in 93	≈ 1 in 6,400
East Asian	~20k	1 in 130	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 190	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 78	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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓