CHRM2 Gene - Cholinergic Receptor Muscarinic 2 | Function, Mutations & Diseases

The CHRM2 gene encodes the M2 subtype of muscarinic acetylcholine receptors, a G protein-coupled receptor (GPCR) that couples primarily to Gi/o proteins. It is widely expressed in the heart, brain, and smooth muscle, where it mediates parasympathetic signaling. In the heart, M2 receptors slow heart rate and reduce contractility; in the brain, they modulate cognitive functions and neurotransmitter release. Genetic variants in CHRM2 have been associated with Alzheimer disease, schizophrenia, and major depressive disorder.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Muscarinic acetylcholine receptor M2 signaling

• Gi-mediated signaling

• Cholinergic synapse

• Cardiac muscarinic signaling

The M2 muscarinic receptor is a 466-amino acid GPCR with seven transmembrane domains. It is activated by acetylcholine and mediates inhibitory responses via Gi/o proteins, leading to decreased cAMP levels, activation of GIRK channels, and modulation of calcium channels. In the heart, it produces negative chronotropic and inotropic effects. In the CNS, it regulates neurotransmitter release and cognitive processes. The receptor is a target for drugs treating Alzheimer disease, cardiac arrhythmias, and psychiatric disorders.