CHRM4 Gene (Cholinergic Receptor Muscarinic 4)
Comprehensive genomic and functional analysis of CHRM4, a key muscarinic acetylcholine receptor involved in neurological and psychiatric disorders.
Gene Information Card
| Symbol | CHRM4 |
|---|---|
| Full Name | Cholinergic Receptor Muscarinic 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 1132 ncbi.nlm.nih.gov/gene/1132 |
| Ensembl ID | ENSG00000180720 |
| UniProt ID | P08173 |
| OMIM ID | 118495 |
| HGNC ID | 1953 |
| Aliases | M4, HM4, M4R, cholinergic receptor, muscarinic 4 |
Description
CHRM4 encodes the M4 muscarinic acetylcholine receptor, a G protein-coupled receptor (GPCR) that mediates the effects of acetylcholine in the central nervous system and peripheral tissues. The M4 receptor is primarily coupled to Gi/o proteins, inhibiting adenylyl cyclase and modulating neuronal excitability. It is highly expressed in the striatum, hippocampus, and cortex, playing critical roles in motor control, cognition, and reward processing. CHRM4 is a target for drug development in schizophrenia, Alzheimer's disease, and Parkinson's disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered M4 receptor signaling in striatal and cortical circuits contributes to cognitive and negative symptoms. | NCBI Gene, OMIM |
| Parkinson's disease | M4 receptor dysfunction in the basal ganglia is implicated in motor and non-motor symptoms. | NCBI Gene, OMIM |
| Alzheimer's disease | Reduced cholinergic signaling and M4 receptor loss in hippocampus correlate with cognitive decline. | NCBI Gene, OMIM |
| Addiction | M4 receptor modulation of dopamine release in nucleus accumbens influences reward and addiction behaviors. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (hippocampus) | 15.2 | Medium |
| Brain (striatum) | 18.7 | High |
| Brain (cerebellum) | 3.1 | Low |
| Heart | 1.2 | Low |
| Lung | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal model |
| U-87 MG (glioblastoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>A (p.Gly38Arg) | Missense | <0.01% | Reduced receptor expression and signaling |
| c.457C>T (p.Arg153Cys) | Missense | <0.01% | Altered ligand binding |
| c.1003G>A (p.Gly335Ser) | Missense | <0.01% | Impaired G protein coupling |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Gly38Arg reduce receptor expression and Gi/o signaling, leading to loss of function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CHRM4.
Dominant Negative (DN)
No dominant-negative mutations described for CHRM4.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • acetylcholine binding |
| • muscarinic acetylcholine receptor activity | • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway |
| • synaptic transmission | • cholinergic |
| • nervous system development |
Pathways
• Muscarinic acetylcholine receptor signaling
• Gi signaling
• cAMP inhibition pathway
• Cholinergic synapse
Protein Summary
The M4 muscarinic acetylcholine receptor is a 479-amino acid protein with seven transmembrane domains, typical of GPCRs. It is predominantly expressed in the brain, especially in the striatum and hippocampus. The receptor inhibits adenylyl cyclase via Gi/o proteins, reducing cAMP levels and modulating neuronal firing. It forms heteroreceptor complexes with dopamine D1 receptors, influencing motor and cognitive functions. CHRM4 is a validated drug target for treating schizophrenia and Parkinson's disease psychosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHRM4 Knockout HEK293 Cell Line | EDJ-KQ50189 | Human | 1132 | Details Get a Quote |
| CHRM4 Knockout HeLa Cell Line | EDJ-KQ52898 | Human | 1132 | Details Get a Quote |
| CHRM4 Knockout A-549 Cell Line | EDJ-KQ61367 | Human | 1132 | Details Get a Quote |
| CHRM4 Knockout HCT 116 Cell Line | EDJ-KQ69863 | Human | 1132 | Details Get a Quote |
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