CHRM3 Gene

HGNC Family	Cholinergic receptors, G protein-coupled receptors
Name	cholinergic receptor, muscarinic 3
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The CHRM3 gene, which encodes the muscarinic acetylcholine receptor subtype M3, plays multifaceted roles in both central and peripheral physiology. In the central nervous system, genetic perturbations of CHRM3—often in combination with CHRM1—have been shown to drastically reduce rapid eye movement sleep and may contribute to epileptogenesis by altering neural connectivity patterns."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In peripheral tissues, CHRM3 signaling exerts inhibitory control over epithelial cell migration during wound reepithelialization"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and is crucial for proper smooth muscle function; for instance, a deleterious frameshift mutation in CHRM3 has been identified as causative of congenital bladder malformation, indicating its importance in urinary tract development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the realm of oncology, aberrant CHRM3 expression contributes to tumor progression in several cancers. In colon cancer, CHRM3 overexpression engages with β‐catenin signaling to promote neoplastic growth"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while in prostate cancer, increased CHRM3 levels enhance cell proliferation, migration, and castration‐resistant growth through downstream activation of pathways such as Akt and YAP via focal adhesion kinase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, CHRM3 modulates metabolic processes in the pancreas; polymorphisms in this gene are associated with a diminished acute insulin response and an increased risk for type 2 diabetes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and specific CHRM3 variants also correlate with a heightened risk of postoperative nausea and vomiting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In addition, therapeutic blockade of CHRM3 has been demonstrated to ameliorate airway hyperreactivity in experimental models of childhood asthma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and CHRM3 polymorphisms have been linked to autoimmune conditions such as primary Sjögren’s syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, evolutionary analyses reveal that transposable element integrations have led to alternative splicing events in the CHRM3 gene, resulting in tissue‐specific expression profiles in organs such as the placenta, testis, and various brain regions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these studies underscore the diverse roles of CHRM3 in regulating sleep, neural connectivity, epithelial and smooth muscle function, metabolic homeostasis, and cancer progression, making it a promising target for therapeutic intervention in a variety of disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasutaka Niwa, Genki N Kanda, Rikuhiro G Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.07.082"}], "href": "https://doi.org/10.1016/j.celrep.2018.07.082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30157420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30157420"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael Steffens, Costin Leu, Ann-Kathrin Ruppert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds373"}], "href": "https://doi.org/10.1093/hmg/dds373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22949513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22949513"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Q Wang, W Cheng, M Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Psychol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0033291716000167"}], "href": "https://doi.org/10.1017/S0033291716000167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26959877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26959877"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alex I Chernyavsky, Juan Arredondo, Jürgen Wess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200401034"}], "href": "https://doi.org/10.1083/jcb.200401034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15263021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15263021"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Stefanie Weber, Holger Thiele, Sevgi Mir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.10.007"}], "href": "https://doi.org/10.1016/j.ajhg.2011.10.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22077972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22077972"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jean-Pierre Raufman, Jasleen Shant, Guofeng Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscarinic receptor subtype-3 gene ablation and scopolamine butylbromide treatment attenuate small intestinal neoplasia in Apcmin/+ mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgr118"}], "href": "https://doi.org/10.1093/carcin/bgr118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21705482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21705482"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Naitao Wang, Ming Yao, Jin Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK-Mediated Phosphorylation of Akt."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-14-3163"}], "href": "https://doi.org/10.1158/1078-0432.CCR-14-3163"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26071486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26071486"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yusuke Goto, Toshinori Ando, Hiroki Izumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscarinic receptors promote castration-resistant growth of prostate cancer through a FAK-YAP signaling axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-1272-x"}], "href": "https://doi.org/10.1038/s41388-020-1272-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32205868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32205868"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yan Guo, Michael Traurig, Lijun Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHRM3 gene variation is associated with decreased acute insulin secretion and increased risk for early-onset type 2 diabetes in Pima Indians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db06-0379"}], "href": "https://doi.org/10.2337/db06-0379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17130513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17130513"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "S Klenke, G J de Vries, L Schiefer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHRM3 rs2165870 polymorphism is independently associated with postoperative nausea and vomiting, but combined prophylaxis is effective."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Anaesth (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bja.2018.02.025"}], "href": "https://doi.org/10.1016/j.bja.2018.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29935595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29935595"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kruti R Patel, Yan Bai, Kenneth G Trieu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201700186R"}], "href": "https://doi.org/10.1096/fj.201700186R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28619712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28619712"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Silke Appel, Stephanie Le Hellard, Ove Bruland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potential association of muscarinic receptor 3 gene variants with primary Sjogren's syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/ard.2010.138966"}], "href": "https://doi.org/10.1136/ard.2010.138966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21450750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21450750"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jae-Won Huh, Young-Hyun Kim, Sang-Rae Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gain of new exons and promoters by lineage-specific transposable elements-integration and conservation event on CHRM3 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10059-009-0106-z"}], "href": "https://doi.org/10.1007/s10059-009-0106-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19669628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19669628"}]}]}]}
Synonyms	HM3, EGBRS
Proteins	ACM3_HUMAN
NCBI Gene ID	1131
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CHRM3 has 7,469 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 130 datasets.

Click the + buttons to view associations for CHRM3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CHRM3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRM3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRM3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CHRM3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CHRM3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CHRM3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHRM3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CHRM3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CHRM3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CHRM3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CHRM3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHRM3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CHRM3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CHRM3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRM3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CHRM3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CHRM3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CHRM3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CHRM3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CHRM3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CHRM3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CHRM3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CHRM3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CHRM3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CHRM3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHRM3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CHRM3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CHRM3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CHRM3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CHRM3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CHRM3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for CHRM3 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CHRM3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CHRM3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CHRM3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CHRM3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CHRM3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CHRM3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CHRM3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CHRM3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRM3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.