CHRM2

protein-coding

cholinergic receptor muscarinic 2, the group of Cholinergic receptors muscarinic|MicroRNA protein coding host genes

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 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]

MANE transcript

NM_001006630.2

Inheritance

—

ClinVar variants

U:129B:91

Top phenotype

Dilated Cardiomyopathy, Dominant

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr7:136,868,652-137,020,255

External References & Databases

Ensembl (ENSG00000181072)

Transcript & Mutation Effects

hg38 • Region Span ~151.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHRM2 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 197

not specifiedTotal: 66

Dilated Cardiomyopathy, DominantTotal: 2

Dilated cardiomyopathy 1ATotal: 1

CardiomyopathyTotal: 1

CHRM2-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001006630.2. 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				76 clinvar	6 clinvar	82
missense			127 clinvar	8 clinvar	1 clinvar	136
nonsense						0
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	129	84	7	220

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001006630.2	RefSeq	NP_001006631.1	1	MANE Select
ENST00000680005.1	Ensembl	ENSP00000505686.1	1	MANE Select
NM_000739.3	RefSeq	NP_000730.1	1	Standard
NM_001006626.3	RefSeq	NP_001006627.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
chrm2a	Danio rerio	Structure: heart contraction Quality: increased rate abnormal

Gene / Model

Organism

Observed Phenotype

chrm2a

Danio rerio

Structure: heart contraction

Quality: increased rate

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
cAMP signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)

Biological Process

regulation of smooth muscle contraction
G protein-coupled receptor signaling pathway
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway

Molecular Function

G protein-coupled receptor activity
G protein-coupled serotonin receptor activity
drug binding
G protein-coupled acetylcholine receptor activity
neurotransmitter receptor activity

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000445907
Coding exons: 1
Length: 151587
Individuals with no LoFs: 125480
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125484
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.92	160	244	0.654	0.0000120	3083
Missense (PolyPhen)		32	101.91	0.31401		1325
Synonymous	-0.271	94	90.7	1.04	0.00000463	924
Loss of Function	2.20	3	10.8	0.278	5.51e-7	144

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)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
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 adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol. {ECO:0000269|PubMed:24256733, ECO:0000269|PubMed:3443095}.;
Disease: DISEASE: Major depressive disorder (MDD) [MIM:608516]: A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. {ECO:0000269|PubMed:15229186}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.536
RVIS EVS: 0.19
RVIS percentile EVS: 67.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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