CHRM3

Chr 1AR

cholinergic receptor muscarinic 3

Also known as: EGBRS, HM3, PBS, m3AChR

NCBI Gene: 1131ENSG00000133019UniProt: P20309

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 3 controls smooth muscle contraction and its stimulation causes secretion of glandular tissue. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

Prune belly syndromeMIM #100100
AR
235
ClinVar variants
63
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— CHRM3
⚡
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
63 Pathogenic / Likely Pathogenic· 114 VUS of 235 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.25LOEUF
pLI 0.993
Z-score 3.83
OE 0.05 (0.02–0.25)
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.
1.96Z-score
OE missense 0.70 (0.63–0.78)
236 obs / 337.2 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.0.05 (0.02–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.63–0.78)
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.1.07
0≤1.21.6
LoF obs/exp: 1 / 19.0Missense obs/exp: 236 / 337.2Syn Z: -0.71

ClinVar Variant Classifications

235 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic3
VUS114
Likely Benign46
Benign10
Conflicting2
60
Pathogenic
3
Likely Pathogenic
114
VUS
46
Likely Benign
10
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
58
0
60
Likely Pathogenic
1
0
2
0
3
VUS
0
84
28
2
114
Likely Benign
0
5
2
39
46
Benign
0
2
4
4
10
Conflicting
—2
Total2929445235

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

View in ClinVar →

Protein Context — Lollipop Plot

CHRM3 · 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

Prune belly syndrome

MIM #100100

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Aberrant PJA2-CHRM3 signaling creates a therapeutic vulnerability in gastric tumor.
Li L et al.·Br J Cancer
2025
Targeting M3 Muscarinic Receptors for Colon Cancer Therapy.
Felton J et al.·Curr Mol Pharmacol
2018Review
Exploring the Target and Mechanism of Radix Paeoniae Alba on Sjogren's Syndrome.
Wu F et al.·Comb Chem High Throughput Screen
2023Functional
Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep.
Niwa Y et al.·Cell Rep
2018
A homozygous missense variant in CHRM3 associated with familial urinary bladder disease.
Beaman GM et al.·Clin Genet
2019
A regulatory variant of CHRM3 is associated with cannabis-induced hallucinations in European Americans.
Cheng Z et al.·Transl Psychiatry
2019
Genetic contribution to PONV risk.
Klenke S et al.·Anaesth Crit Care Pain Med
2020
Identification of telomere-related lncRNAs and immunological analysis in ovarian cancer.
Xu W et al.·Front Immunol
2024
Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK-Mediated Phosphorylation of Akt.
Wang N et al.·Clin Cancer Res
2015
Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids.
Laugsand EA et al.·Eur J Cancer
2011Cohort
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
Amyotrophic Lateral Sclerosis

A Study to Assess the Safety, Tolerability, and Pharmacology of Darifenacin in Patients With ALS

RECRUITING
NCT06249867Phase PHASE2Oliver BlanchardStarted 2024-11-08
Darifenacin 7.5 MG Extended Release Oral TabletPlacebo

External Resources

Links to major genomics databases and tools