CHRM2

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

Basic information

Region (hg38): 7:136868651-137020255

Links

ENSG00000181072 ∙ NCBI:1129 ∙ OMIM:118493 ∙ HGNC:1951 ∙ Uniprot:P08172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRM2 gene.

• Dilated Cardiomyopathy, Dominant (130 variants)
• not provided (32 variants)
• not specified (23 variants)
• Inborn genetic diseases (11 variants)
• Cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRM2 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			1	43	7	51
missense			79	6	1	86
nonsense						0
start loss			1			1
frameshift			1			1
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				9	18	27
Total	0	0	84	58	26

Variants in CHRM2

This is a list of pathogenic ClinVar variants found in the CHRM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-136868746-GCA-G			Benign (Nov 15, 2019)
7-136868746-GCACA-G			Likely benign (Nov 15, 2019)
7-136868746-GCACACA-G			Benign (May 29, 2020)
7-136868746-GCACACACACACACACA-G			Benign (Nov 12, 2019)
7-136869177-G-C		not specified	Likely benign (Aug 09, 2017)
7-136869187-C-G			Likely benign (May 02, 2018)
7-136869192-C-T		not specified	Likely benign (Mar 31, 2017)
7-136869276-G-A		not specified	Benign (Oct 26, 2016)
7-136869413-C-T		not specified	Benign (Oct 19, 2016)
7-136950783-CTGT-C			Benign (Dec 16, 2019)
7-136950783-C-CTGT			Benign (Feb 03, 2020)
7-136950783-C-CTGTTGT			Benign (Apr 27, 2020)
7-136950804-T-A			Benign (Nov 12, 2019)
7-136950870-C-T			Benign (Jun 23, 2018)
7-136951002-G-A			Benign (Jul 12, 2021)
7-136951029-G-T			Benign (Jul 12, 2021)
7-136992195-C-T		not specified	Likely benign (Nov 15, 2017)
7-136992219-T-C			Likely benign (Jun 25, 2020)
7-136992241-T-C			Benign (Apr 27, 2020)
7-136992247-C-G		not specified	Benign (Dec 07, 2016)
7-136992262-A-T		not specified	Likely benign (Jan 16, 2017)
7-136992263-T-G		not specified	Likely benign (Apr 27, 2017)
7-137014492-T-C			Likely benign (Jun 14, 2018)
7-137014514-G-T			Benign (Jun 19, 2018)
7-137014618-T-C			Likely benign (Jun 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRM2	protein_coding	protein_coding	ENST00000445907	1	151587

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.182	0.807	125480	0	4	125484	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	160	244	0.654	0.0000120	3083
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
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 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.
• Pathway: 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);Cholinergic synapse - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;GPCRs, Other;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;GPCRs, Class A Rhodopsin-like;Regulation of Actin Cytoskeleton;Calcium Regulation in the Cardiac Cell;Monoamine GPCRs;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by GPCR;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Muscarinic acetylcholine receptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.536
• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.312
• hipred: Y
• hipred_score: 0.564
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrm2
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Zebrafish Information Network

• Gene name: chrm2a
• Affected structure: heart contraction
• Phenotype tag: abnormal
• Phenotype quality: increased rate

Gene ontology

• 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;phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway;G protein-coupled acetylcholine receptor signaling pathway;chemical synaptic transmission;nervous system development;regulation of heart contraction;response to virus;membrane organization;G protein-coupled serotonin receptor signaling pathway;regulation of synaptic vesicle exocytosis
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;cell junction;dendrite;clathrin-coated vesicle membrane;asymmetric synapse;symmetric synapse;neuronal cell body;axon terminus;glutamatergic synapse;cholinergic synapse;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: G protein-coupled receptor activity;G protein-coupled serotonin receptor activity;drug binding;G protein-coupled acetylcholine receptor activity;neurotransmitter receptor activity;arrestin family protein binding