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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MCHR2
melanin concentrating hormone receptor 2
Chromosome 6 · 6q16.2
NCBI Gene: 84539Ensembl: ENSG00000152034.12HGNC: HGNC:20867UniProt: Q969V1
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
melanin-concentrating hormone receptor activityG protein-coupled receptor signaling pathwayphospholipase C-activating G protein-coupled receptor signaling pathwayprotein bindingneurodegenerative diseaseatrial fibrillationgallbladder diseaseerectile dysfunction
✦AI Summary

MCHR2 (melanin concentrating hormone receptor 2) is a G protein-coupled receptor located on chromosome 6 that serves as one of two receptors for the neuropeptide melanin-concentrating hormone (MCH) 1. Unlike its homolog MCHR1, MCHR2 is expressed only in carnivores, primates, and humans 2. The receptor binds MCH with high affinity and signals through Gq protein activation, triggering phosphoinositide hydrolysis and intracellular calcium release 3. MCHR2 is distributed across multiple brain regions and participates in energy homeostasis regulation, feeding behavior, and metabolism 4. While MCH signaling through both receptors influences sleep-wake rhythms, anxiety, depression, and reproduction, the specific role of MCHR2 in these processes remains incompletely characterized due to limited animal models 2. Genetic studies identify MCHR2 associations with body mass index, particularly in younger individuals with atypical depression 5, though MCHR2 appears not to be a major contributor to human obesity phenotypes 6. A genome-wide association study variant in MCHR2-AS1 showed association with tic disorders, though this finding lacked replication 7. MCHR2 represents a potential therapeutic target for metabolic and psychiatric disorders involving energy balance dysregulation.

Sources cited
1
MCHR2 is a G protein-coupled receptor for MCH located at chromosome 6q21, signals through Gq protein
PMID: 11416225
2
MCHR2 binds MCH and activates phosphoinositide hydrolysis/Ca2+ release with high affinity
PMID: 20099459
3
MCHR2 knockdown affects MCH binding and intracellular calcium signaling
PMID: 20937223
4
MCHR2 genetic variants associated with BMI, particularly in younger individuals with atypical depression
PMID: 26461262
5
MCH and its receptors including MCHR2 regulate feeding, metabolism, sleep-wake rhythms, and emotional states
PMID: 34608277
6
MCHR2 is expressed only in carnivores, primates, and humans; specific role in sleep regulation unclear
PMID: 23477948
7
MCHR2 is not a major contributor to human obesity and Prader-Willi-like phenotype
PMID: 29066024
8
MCHR2-AS1 variant associated with tic disorders in GWAS, but lacked replication
PMID: 39389409
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.32Weak
atrial fibrillationOpen Targets
0.32Weak
gallbladder diseaseOpen Targets
0.31Weak
erectile dysfunctionOpen Targets
0.31Weak
osteoarthritisOpen Targets
0.31Weak
testicular diseaseOpen Targets
0.30Weak
vertebral column disorderOpen Targets
0.29Weak
osteitis deformansOpen Targets
0.27Weak
edemaOpen Targets
0.25Weak
chronic venous insufficiencyOpen Targets
0.24Weak
obesityOpen Targets
0.23Weak
atrial flutterOpen Targets
0.21Weak
HypercholesterolemiaOpen Targets
0.21Weak
alcohol drinkingOpen Targets
0.21Weak
drug allergyOpen Targets
0.20Weak
heart failureOpen Targets
0.20Weak
Abnormality of the genital systemOpen Targets
0.19Weak
osteoarthritis, kneeOpen Targets
0.19Weak
attention deficit hyperactivity disorderOpen Targets
0.18Weak
glomerulonephritisOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GPR139Shared pathway100%MCHR1Protein interaction92%PMCHProtein interaction92%SIM1Protein interaction82%GPR83Shared pathway67%TRHRShared pathway50%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
1%
Heart
0%
Lung
0%
Ovary
0%
Liver
0%
Gene Interaction Network
Click a node to explore
MCHR2GPR139MCHR1PMCHSIM1GPR83TRHR
PROTEIN STRUCTURE
Preparing viewer…
PDB8WST · 2.40 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.65 [0.44–0.97]
RankingsWhere MCHR2 stands among ~20K protein-coding genes
  • #11,543of 20,598
    Most Researched32
  • #9,254of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedMCHR2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Establishment of CHO cell line expressing human MCHR2 gene and research of its molecular characteristics.
PMID: 20099459
Indian J Exp Biol · 2009
1.00
2
Generation of mammalian cell lines with gene knock-down for human MCHR2.
PMID: 20937223
Cell Mol Biol (Noisy-le-grand) · 2010
0.90
3
Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression.
PMID: 26461262
PLoS One · 2015
0.80
4
Genome-Wide Association Study Meta-Analysis of 9619 Cases With Tic Disorders.
PMID: 39389409
Biol Psychiatry · 2025
0.70
5
Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis.
PMID: 34608277
Nat Rev Endocrinol · 2021
0.60