CHRM1 is a human gene whose product the Muscarinic Acetylcholine Receptor M2 (CHRM2) is a G protein-coupled receptor (GPCR) that mediates the effects of acetylcholine on slow inhibitory postsynaptic potentials in the heart, smooth muscle, and neurons 1. CHRM2 is coupled to Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of inwardly rectifying potassium channels (GIRK), and suppression of neuronal excitability 2. Variants in CHRM1 have been implicated in Alzheimer's Disease, Schizophrenia, Cardiac Function. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [1]
| Gene Symbol | CHRM2 |
|---|---|
| Full Name | Cholinergic Receptor Muscarinic 2 |
| Chromosomal Location | 7q31-q36 |
| NCBI Gene ID | https://www.ncbi.nlm.nih.gov/gene/1128 1128 |
| OMIM | https://www.omim.org/entry/118510 118510 |
| Ensembl ID | ENSG00000131617 |
| UniProt ID | https://www.uniprot.org/uniprot/P08172 P08172 |
| Associated Diseases | Alzheimer's disease, schizophrenia, cardiac dysfunction |
The Muscarinic Acetylcholine Receptor M2 (CHRM2) is a G protein-coupled receptor (GPCR) that mediates the effects of acetylcholine on slow inhibitory postsynaptic potentials in the heart, smooth muscle, and neurons 1. CHRM2 is coupled to Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of inwardly rectifying potassium channels (GIRK), and suppression of neuronal excitability 2.
In the central nervous system, CHRM2 is highly expressed in the hippocampus, cerebral cortex, and basal ganglia, where it modulates learning, memory, and reward processing 3. The receptor plays a critical role in cholinergic signaling through the septohippocampal pathway, which is essential for spatial memory and attention.
CHRM2 genetic variants are associated with altered risk for Alzheimer's disease 4. The cholinergic hypothesis of AD posits that loss of muscarinic receptor signaling contributes to cognitive decline. CHRM2 agonists have been investigated as potential therapeutics to enhance cholinergic neurotransmission 5.
CHRM2 polymorphisms are linked to schizophrenia susceptibility and treatment response 6. Altered CHRM2 expression has been observed in postmortem brain tissue from schizophrenia patients, particularly in the prefrontal cortex.
CHRM2 is the primary muscarinic receptor in the heart, mediating vagal slowing of heart rate (negative chronotropy) 7. CHRM2 activation opens GIRK channels, hyperpolarizing cardiac pacemaker cells.
CHRM2 exhibits region-specific expression in the nervous system:
| Variant | Type | Effect | Disease Association |
|---|---|---|---|
| rs1824024 | SNP | Altered expression | AD risk |
| rs324640 | SNP | Synonymous | Schizophrenia |
| rs6962022 | SNP | 3' UTR | Substance abuse |
| rs2350780 | SNP | Intronic | Cardiac function |