MCHR1 (Melanin Concentrating Hormone Receptor 1)
G protein-coupled receptor for melanin-concentrating hormone, involved in energy homeostasis, feeding behavior, and mood regulation.
Gene Information Card
| Symbol | MCHR1 |
|---|---|
| Full Name | Melanin Concentrating Hormone Receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q13.3 |
| NCBI Gene ID | 2847 ncbi.nlm.nih.gov/gene/2847 |
| Ensembl ID | ENSG00000128285 |
| UniProt ID | Q99705 |
| OMIM ID | 601751 |
| HGNC ID | 6946 |
| Aliases | GPR24, SLC1, MCH1, MCHR1L |
Description
MCHR1 encodes a G protein-coupled receptor (GPCR) for melanin-concentrating hormone (MCH). It is primarily expressed in the brain and plays a critical role in regulating energy balance, feeding behavior, body weight, and mood. Activation of MCHR1 by MCH leads to inhibition of cAMP accumulation via Gi/o proteins. The receptor is a target for anti-obesity and psychiatric drug development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | MCHR1 signaling promotes food intake; antagonism reduces body weight in animal models. | Animal studies; clinical trials with antagonists (e.g., ALB-127158). |
| Anxiety | MCHR1 activation modulates stress responses; knockout mice show reduced anxiety-like behavior. | Mouse knockout studies (e.g., Roy et al., 2006). |
| Depression | MCHR1 antagonists exhibit antidepressant-like effects in rodent models. | Preclinical pharmacology (e.g., Borowsky et al., 2002). |
| Sleep Disorders | MCHR1 involved in REM sleep regulation via hypothalamic circuits. | Electrophysiological and lesion studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (hypothalamus) | 12.5 | High |
| Brain (amygdala) | 8.3 | Medium |
| Brain (hippocampus) | 6.7 | Medium |
| Brain (cortex) | 5.1 | Low |
| Testis | 2.0 | Low |
| Adipose tissue | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 4.2 | Endogenous expression |
| HEK293 (embryonic kidney) | 0.1 | Low; used for recombinant expression |
| SK-N-SH (neuroblastoma) | 3.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs133073 (c.839C>T) | missense (p.Thr280Met) | <0.01% in gnomAD | Unknown functional effect |
| rs61734410 (c.100G>A) | missense (p.Val34Ile) | 0.02% in gnomAD | Likely benign |
| c.1A>G | start loss | Very rare | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Start-loss mutations (e.g., c.1A>G) predicted to abolish protein expression.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative variants described.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • melanin-concentrating hormone receptor activity (GO:0004965) |
| • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193) | • feeding behavior (GO:0007631) |
| • positive regulation of ERK1 and ERK2 cascade (GO:0070374) | • plasma membrane (GO:0005886) |
Pathways
• GPCR downstream signaling (Gi/o) – inhibition of cAMP production
• MCH signaling pathway (Reactome: R-HSA-388479)
• Neuropeptide signaling in energy homeostasis (KEGG: hsa04923)
Protein Summary
MCHR1 is a 353-amino-acid integral membrane protein with seven transmembrane domains, typical of class A GPCRs. It binds melanin-concentrating hormone (MCH) with high affinity. Upon activation, it couples primarily to Gi/o proteins, inhibiting adenylyl cyclase and reducing intracellular cAMP. The receptor also activates MAPK/ERK pathways. It is predominantly expressed in the central nervous system, especially in the hypothalamus, amygdala, and hippocampus, where it regulates feeding, energy expenditure, stress, and mood. MCHR1 antagonists are under investigation for obesity, anxiety, and depression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MCHR1 Knockout HEK293 Cell Line | EDJ-KQ4767 | Human | 2847 | Details Get a Quote |
| MCHR1 Knockout HeLa Cell Line | EDJ-KQ53400 | Human | 2847 | Details Get a Quote |
| MCHR1 Knockout A-549 Cell Line | EDJ-KQ61877 | Human | 2847 | Details Get a Quote |
| MCHR1 Knockout HCT 116 Cell Line | EDJ-KQ70358 | Human | 2847 | Details Get a Quote |
