CHRM3

cholinergic receptor muscarinic 3, the group of Cholinergic receptors muscarinic

Basic information

Region (hg38): 1:239386565-239915452

Links

ENSG00000133019 ∙ NCBI:1131 ∙ OMIM:118494 ∙ HGNC:1952 ∙ Uniprot:P20309 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• prune belly syndrome (Strong), mode of inheritance: AR
• prune belly syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Prune belly syndrome (Eagle-Barrett syndrome)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary; Musculoskeletal; Renal	14797335; 15912376; 22077972; 31441039

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRM3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRM3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				29	2	31
missense			23	3	2	28
nonsense						0
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1		4	5
Total	0	0	26	32	8

Variants in CHRM3

This is a list of pathogenic ClinVar variants found in the CHRM3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-239548263-G-A		Prune belly syndrome	Uncertain significance (Jun 23, 2021)
1-239907303-T-C			Benign (Nov 12, 2018)
1-239907460-G-A			Likely benign (Mar 14, 2023)
1-239907463-C-T			Likely benign (Dec 30, 2022)
1-239907480-C-T		not specified	Uncertain significance (Feb 28, 2023)
1-239907543-C-G			Uncertain significance (Oct 17, 2022)
1-239907544-G-A			Likely benign (Mar 27, 2022)
1-239907572-A-G		not specified	Uncertain significance (Aug 08, 2022)
1-239907582-G-A			Uncertain significance (Jul 07, 2023)
1-239907610-C-T		CHRM3-related disorder	Benign (Apr 15, 2023)
1-239907643-C-T		CHRM3-related disorder	Likely benign (Jul 25, 2022)
1-239907644-G-A			Benign (Feb 01, 2024)
1-239907665-G-A			Uncertain significance (Mar 13, 2022)
1-239907734-G-A		not specified	Uncertain significance (May 31, 2023)
1-239907779-C-T		Prune belly syndrome	Likely benign (Jan 24, 2023)
1-239907803-G-A		Prune belly syndrome	Pathogenic (Aug 04, 2020)
1-239907820-T-C			Likely benign (Apr 12, 2023)
1-239907835-C-T			Likely benign (Jun 15, 2018)
1-239907866-T-C			Likely benign (May 22, 2023)
1-239907901-A-T			Likely benign (Jun 27, 2022)
1-239907964-G-C			Likely benign (Sep 01, 2023)
1-239908009-T-C			Likely benign (Apr 06, 2022)
1-239908042-T-G			Uncertain significance (Dec 22, 2023)
1-239908132-T-C		Prune belly syndrome	Likely benign (Mar 12, 2023)
1-239908253-C-T			Likely benign (Jun 14, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRM3	protein_coding	protein_coding	ENST00000255380	1	528886

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00747	125699	0	2	125701	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.96	236	337	0.700	0.0000197	3882
Missense in Polyphen		25	98.03	0.25502		1156
Synonymous	-0.705	158	147	1.07	0.0000103	1184
Loss of Function	3.83	1	19.0	0.0525	0.00000120	195

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000104	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. {ECO:0000269|PubMed:7565628}.
• Disease: DISEASE: Prune belly syndrome (PBS) [MIM:100100]: A syndrome characterized by thin abdominal musculature with overlying lax skin, cryptorchism, megacystis with disorganized detrusor muscle, and urinary tract abnormalities. {ECO:0000269|PubMed:22077972}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric acid secretion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Taste transduction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Pantoprazole Action Pathway;Rabeprazole Action Pathway;Esomeprazole Action Pathway;Omeprazole Action Pathway;Lansoprazole Action Pathway;Gastric Acid Production;Nizatidine Action Pathway;Cimetidine Action Pathway;Famotidine Action Pathway;Ranitidine Action Pathway;Betazole Action Pathway;Roxatidine acetate Action Pathway;Metiamide Action Pathway;Pirenzepine Action Pathway;GPCRs, Other;GPCRs, Class A Rhodopsin-like;Regulation of Actin Cytoskeleton;Calcium Regulation in the Cardiac Cell;Monoamine GPCRs;Signaling by GPCR;Signal Transduction;Metabolism;Muscarinic acetylcholine receptors;Acetylcholine regulates insulin secretion;Amine ligand-binding receptors;Regulation of insulin secretion;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Integration of energy metabolism;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.205
• hipred: Y
• hipred_score: 0.792
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.851

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Chrm3
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; muscle phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype

Gene ontology

• Biological process: regulation of vascular smooth muscle contraction;cellular protein modification process;smooth muscle contraction;signal transduction;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway;G protein-coupled acetylcholine receptor signaling pathway;chemical synaptic transmission;synaptic transmission, cholinergic;nervous system development;cell population proliferation;positive regulation of smooth muscle contraction;saliva secretion;G protein-coupled serotonin receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;basolateral plasma membrane;cell junction;dendrite;axon terminus;glutamatergic synapse;integral component of presynaptic membrane;integral component of postsynaptic density membrane
• Molecular function: phosphatidylinositol phospholipase C activity;G protein-coupled receptor activity;G protein-coupled serotonin receptor activity;protein binding;G protein-coupled acetylcholine receptor activity;neurotransmitter receptor activity;signaling receptor activity;acetylcholine binding