CHRM2

Chr 7

cholinergic receptor muscarinic 2

Also known as: HM2

NCBI Gene: 1129ENSG00000181072UniProt: P08172

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 to these receptors 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 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtMajor depressive disorder
288
ClinVar variants
37
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— CHRM2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 134 VUS of 288 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.72LOEUF
pLI 0.182
Z-score 2.20
OE 0.28 (0.13–0.72)
Tolerant

Typical tolerance to LoF variation

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.
1.92Z-score
OE missense 0.65 (0.57–0.75)
160 obs / 244.5 exp
Tolerant

Mild missense constraint

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.0.28 (0.13–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.75)
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.1.04
0≤1.21.6
LoF obs/exp: 3 / 10.8Missense obs/exp: 160 / 244.5Syn Z: -0.27

ClinVar Variant Classifications

288 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic1
VUS134
Likely Benign89
Benign26
Conflicting2
36
Pathogenic
1
Likely Pathogenic
134
VUS
89
Likely Benign
26
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
1
0
1
VUS
1
124
9
0
134
Likely Benign
0
6
11
72
89
Benign
1
1
17
7
26
Conflicting
—2
Total21317479288

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

View in ClinVar →

Protein Context — Lollipop Plot

CHRM2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Polymorphism of CHRM2 in COPD: Clinical Significance and Therapeutic Implications.
Cherubini E et al.·J Cell Physiol
2016
CHRM2 variation predisposes to personality traits of agreeableness and conscientiousness.
Luo X et al.·Hum Mol Genet
2007
The Role of Muscarinic Receptors in the Pathophysiology of Mood Disorders: A Potential Novel Treatment?
Jeon WJ et al.·Curr Neuropharmacol
2015Review
A cholinergic receptor gene (CHRM2) affects event-related oscillations.
Jones KA et al.·Behav Genet
2006
A missense mutation in the CHRM2 gene is associated with familial dilated cardiomyopathy.
Zhang L et al.·Circ Res
2008
Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome.
Wang JC et al.·Hum Mol Genet
2004
Pharmacogenetics of asthma controller treatment.
Mougey EB et al.·Pharmacogenomics J
2013
Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations.
Takagi Y et al.·Neurol Med Chir (Tokyo)
2014Review
A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder.
Isali I et al.·Am J Obstet Gynecol
2023Review
Unravelling of the comparative Transcriptomic Profile of Gallbladder Cancer using mRNA sequencing.
Dixit R et al.·Mol Biol Rep
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CHRM2 and GRIN2A polymorphisms in tardive dyskinesia and cognitive impairments in Chinese Han schizophrenia.
Lu C et al.·J Neural Transm (Vienna)
2025
The active ingredient β-sitosterol in Ganoderma regulates CHRM2-mediated aerobic glycolysis to induce apoptosis of lung adenocarcinoma cells.
Zhao Q et al.·Genes Genet Syst
2025
Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case-control study.
Al-Eitan LN et al.·Pharmgenomics Pers Med
2019🔓 Open Access
CHRM2 Genotype Affects Inhibitory Control Mechanisms During Cognitive Flexibility.
Zink N et al.·Mol Neurobiol
2019Functional
Pharmacogenetics of tardive dyskinesia in schizophrenia: The role of CHRM1 and CHRM2 muscarinic receptors.
Boiko AS et al.·World J Biol Psychiatry
2020
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