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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MCHR1
melanin concentrating hormone receptor 1
Chromosome 22 · 22q13.2
NCBI Gene: 2847Ensembl: ENSG00000128285.5HGNC: HGNC:4479UniProt: Q99705
52PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ciliumadenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayprotein bindingplasma membranecarpal tunnel syndromenerve plexus diseaseAbnormality of the skeletal systembreast carcinoma
✦AI Summary

MCHR1 is a G protein-coupled receptor that mediates melanin-concentrating hormone (MCH) signaling through dual pathways: inhibition of adenylyl cyclase and activation of phosphoinositide hydrolysis 1. The receptor localizes to primary cilia and plasma membranes, where MCH binding triggers Akt phosphorylation and downstream effects on cilia length and cellular calcium mobilization 12. MCHR1 plays central roles in energy homeostasis and feeding behavior regulation 3. Beyond its neuronal functions, MCHR1 is expressed in immune cells where it exerts immunomodulatory effects, decreasing CD3-stimulated lymphocyte proliferation and modulating cAMP synthesis 2. Clinical significance centers on metabolic and neuropsychiatric disease. MCHR1 emerged as a druggable target robustly linked to bipolar disorder through expression quantitative trait locus analyses in a 41,917-case genome-wide association study 4. MCHR1 antagonists have been explored as anti-obesity therapeutics, though clinical validation remains incomplete 5. DNA methylation of MCHR1 shows allele-specific, age-dependent, and BMI-associated patterns that affect transcription, potentially explaining variable genetic associations across populations 6. Additionally, elevated serum anti-MCHR1 antibodies appear enriched in vitiligo patients (16.55% vs controls), suggesting possible autoimmune involvement 7.

Sources cited
1
MCHR1 is a ciliary GPCR that mediates MCH-induced cilia shortening through Akt phosphorylation; MCH triggers calcium mobilization
PMID: 39115281
2
MCHR1 is expressed in immune cells and triggers cAMP synthesis and calcium mobilization; MCH decreases lymphocyte proliferation
PMID: 12220661
3
MCH is a brain-expressed neuropeptide that influences food intake and energy expenditure regulation
PMID: 18221212
4
MCHR1 is a druggable target robustly linked to bipolar disorder via gene expression in large GWAS of 41,917 cases
PMID: 34002096
5
MCHR1 antagonism is proposed for obesity treatment; six compounds progressed to clinical trials but clinical validation is incomplete
PMID: 27595423
6
MCHR1 DNA methylation is allele-specific, age-dependent, BMI-associated, and affects transcription
PMID: 21637341
7
Anti-MCHR1 antibodies are significantly enriched in vitiligo patient sera (16.55%), suggesting possible autoimmune involvement
PMID: 21369690
Disease Associationsⓘ20
carpal tunnel syndromeOpen Targets
0.32Weak
nerve plexus diseaseOpen Targets
0.31Weak
Abnormality of the skeletal systemOpen Targets
0.30Weak
breast carcinomaOpen Targets
0.26Weak
triple-negative breast cancerOpen Targets
0.21Weak
luminal A breast carcinomaOpen Targets
0.19Weak
diverticular diseaseOpen Targets
0.19Weak
breast neoplasmOpen Targets
0.18Weak
bipolar disorderOpen Targets
0.13Weak
schizophreniaOpen Targets
0.10Weak
agingOpen Targets
0.07Suggestive
alcohol drinkingOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
obesity due to melanocortin 4 receptor deficiencyOpen Targets
0.06Suggestive
Kallmann syndromeOpen Targets
0.06Suggestive
coronary artery diseaseOpen Targets
0.05Suggestive
depressive disorderOpen Targets
0.05Suggestive
severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiencyOpen Targets
0.05Suggestive
osteoporosisOpen Targets
0.05Suggestive
obesityOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BBS5Protein interaction100%TTC8Protein interaction100%BBIP1Protein interaction100%BBS7Protein interaction100%PMCHProtein interaction100%MCHR2Protein interaction92%
Tissue Expression6 tissues
Ovary
100%
Brain
63%
Liver
61%
Heart
19%
Lung
4%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
MCHR1BBS5TTC8BBIP1BBS7PMCHMCHR2
PROTEIN STRUCTURE
Preparing viewer…
PDB8WWK · 2.61 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.60 [0.39–0.95]
RankingsWhere MCHR1 stands among ~20K protein-coding genes
  • #8,581of 20,598
    Most Researched52
  • #8,878of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedMCHR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.
PMID: 34002096
Nat Genet · 2021
1.00
2
Ciliary length variations impact cilia-mediated signaling and biological responses.
PMID: 39115281
J Biochem · 2024
0.90
3
Mutation analysis of the MCHR1 gene in human obesity.
PMID: 15941924
Eur J Endocrinol · 2005
0.80
4
Human immune cells express ppMCH mRNA and functional MCHR1 receptor.
PMID: 12220661
FEBS Lett · 2002
0.70
5
Allele-specific, age-dependent and BMI-associated DNA methylation of human MCHR1.
PMID: 21637341
PLoS One · 2011
0.60