CHRM1

Chr 11

cholinergic receptor muscarinic 1

Also known as: HM1, M1, M1R

NCBI Gene: 1128 ENSG00000168539 UniProt: P11229

The muscarinic acetylcholine receptor 1 mediates cellular responses including adenylate cyclase inhibition, phosphoinositide breakdown, and potassium channel modulation through G protein signaling, with roles in bronchoconstriction and gastrointestinal acid secretion. Mutations cause neurodevelopmental disorder with involuntary movements, an autosomal dominant condition affecting the central nervous system. This gene is highly constrained against loss-of-function variants (pLI = 0.99), indicating that such mutations are likely to have severe effects.

ResearchSummary from RefSeq, UniProt

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 muscarinic cholinergic receptor 1 is involved in mediation of vagally-induced bronchoconstriction and in the acid secretion of the gastrointestinal tract. The gene encoding this receptor is localized to 11q13. [provided by RefSeq, Jul 2008]

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 0.991

Z-score 3.47

OE 0.00 (0.00–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.76Z-score

OE missense 0.55 (0.48–0.62)

160 obs / 293.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.21)

0≤0.351.4

Missense OE?0.55 (0.48–0.62)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 0 / 14.0Missense obs/exp: 160 / 293.1Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in CHRM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

365 rare PASS variants

Rare truncating (LoF)

1 in 24,000

13 rare PASS variants

Rare synonymous (reference)

1 in 190

247 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRM1. 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 260	1 in 22,000
South Asian	~43k	1 in 180	none seen
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 30,000
European (Finnish)	~27k	1 in 770	≈ 1 in 25,000
Admixed American	~22k	1 in 230	none seen
African / African American	~21k	1 in 220	≈ 1 in 21,000
East Asian	~20k	1 in 190	none seen
Ashkenazi Jewish	~13k	1 in 590	none seen
Middle Eastern	~2,884	1 in 260	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 ↓