CHRM1

Chr 11

cholinergic receptor muscarinic 1

Also known as: HM1, M1, M1R

NCBI Gene: 1128ENSG00000168539UniProt: P11229

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]

64
ClinVar variants
12
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CHRM1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 47 VUS of 64 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.48–0.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 0 / 14.0Missense obs/exp: 160 / 293.1Syn Z: 0.28

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic5
VUS47
Likely Benign3
Benign2
7
Pathogenic
5
Likely Pathogenic
47
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
1
4
0
5
VUS
0
41
5
1
47
Likely Benign
0
0
0
3
3
Benign
0
0
0
2
2
Total04216664

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CHRM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CHRM1-related intellectual disability

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness.
Renz BW et al.·Cancer Discov
2018
Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention.
Youhanna S et al.·Adv Sci (Weinh)
2025Functional
Loss of Cholinergic Receptor Muscarinic 1 (CHRM1) Protein in the Hippocampus and Temporal Cortex of a Subset of Individuals with Alzheimer's Disease, Parkinson's Disease, or Frontotemporal Dementia: Implications for Patient Survival.
Sabbir MG et al.·J Alzheimers Dis
2022
Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep.
Niwa Y et al.·Cell Rep
2018
Cholinergic signaling via muscarinic M1 receptor confers resistance to docetaxel in prostate cancer.
Wang J et al.·Cell Rep Med
2024
The Cholinergic System: An Emerging Drug Target for Schizophrenia.
Gibbons A et al.·Curr Pharm Des
2016Review
Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia.
Lin HJ et al.·Mol Vis
2009
Lower levels of cortical [(3)H]pirenzepine binding to postmortem tissue defines a sub-group of older people with schizophrenia with less severe cognitive deficits.
Dean B et al.·Schizophr Res
2023
Repurposing of dipeptidyl peptidase FDA-approved drugs in Alzheimer's disease using network pharmacology and in-silico approaches.
Roney M et al.·Comput Biol Chem
2025
Widespread Changes in Positive Allosteric Modulation of the Muscarinic M1 Receptor in Some Participants With Schizophrenia.
Hopper S et al.·Int J Neuropsychopharmacol
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools