CHRM3

protein-coding

cholinergic receptor muscarinic 3, the group of Cholinergic receptors muscarinic

Gene summary

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]

MANE transcript

NM_001375978.1

Inheritance

AR, AD

ClinVar variants

P:3U:88B:53

Top phenotype

Prune belly syndrome (Eagle-Barrett syndrome)

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr1:239,386,565-239,915,452

External References & Databases

Ensembl (ENSG00000133019)

Transcript & Mutation Effects

hg38 • Region Span ~528.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

prune belly syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007032

Submitter: Labcorp Genetics (formerly Invitae)

prune belly syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007032

Submitter: Orphanet

Clinical Genomic Database (CGD)

Prune belly syndrome (Eagle-Barrett syndrome)AR

Manifestation: Genitourinary; Musculoskeletal; Renal

Intervention: General

Rationale: 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

Refs: 14797335; 15912376; 22077972; 31441039

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHRM3 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 64

Prune belly syndromeTotal: 57

not specifiedTotal: 54

CHRM3-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001375978.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	41 clinvar	3 clinvar	47
missense	1 clinvar		83 clinvar	7 clinvar	2 clinvar	93
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)						0
Total	2	1	88	48	5	144

Highest pathogenic variant AF is 6.8404506e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 92 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001375978.1	RefSeq	NP_001362907.1	1	MANE Select
ENST00000676153.1	Ensembl	ENSP00000502667.1	1	MANE Select
NM_000740.4	RefSeq	NP_000731.1	1	Standard
NM_001347716.2	RefSeq	NP_001334645.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

regulation of vascular smooth muscle contraction
cellular protein modification process
smooth muscle contraction
signal transduction
G protein-coupled receptor signaling pathway

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

Cellular Component

plasma membrane
integral component of plasma membrane
basolateral plasma membrane
cell junction
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255380
Coding exons: 1
Length: 528886
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125701
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.96	236	337	0.700	0.0000197	3882
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000010	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.104

Intolerance Scores

RVIS EVS: -0.14
RVIS percentile EVS: 43.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.851

Gene Damage Prediction

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