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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MC3R
melanocortin 3 receptor
Chromosome 20 · 20q13.2
NCBI Gene: 4159Ensembl: ENSG00000124089.4HGNC: HGNC:6931UniProt: P41968
111PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingneuropeptide bindingcorticotropin receptor activityregulation of feeding behavioralcohol drinkingjoint diseasecrush injuryacute tonsillitis
✦AI Summary

MC3R (melanocortin 3 receptor) is a G protein-coupled receptor that serves as a central regulator of energy homeostasis and developmental timing. The receptor binds melanocyte-stimulating hormones and ACTH, activating cAMP-dependent signaling pathways to control multiple physiological processes 1. MC3R plays distinct roles from the related MC4R, with MC3R primarily regulating calorie disposition into growth, lean mass, and sexual maturation timing rather than calorie acquisition 2. Loss-of-function mutations in MC3R are associated with delayed puberty, reduced linear growth, decreased lean mass, and lower IGF1 levels in humans 2. The receptor also functions in peripheral tissues, particularly the liver, where it regulates lipid droplet autophagy and hepatic steatosis through activation of autophagy pathways 3. Common MC3R polymorphisms (Thr6Lys and Val81Ile) show associations with childhood obesity, with homozygous carriers of the Thr6Lys variant having a 3.10-fold increased risk of overweight/obesity 4. Beyond metabolic functions, MC3R contributes to circadian rhythm regulation and has emerging roles in ocular homeostasis and immune privilege 5. The receptor represents a promising therapeutic target for metabolic disorders, with specific agonists showing potential for treating obesity and fatty liver disease 6.

Sources cited
1
MC3R is a GPCR that regulates energy homeostasis through cAMP signaling
PMID: 36053086
2
MC3R regulates growth, puberty timing, and lean mass rather than calorie acquisition
PMID: 34732894
3
Loss-of-function mutations cause delayed puberty and reduced growth in humans
PMID: 34732894
4
MC3R regulates hepatic lipid droplet autophagy and liver steatosis
PMID: 40247435
5
Common MC3R variants associate with childhood obesity risk
PMID: 29688747
6
MC3R has roles in ocular homeostasis and immune privilege
PMID: 37217094
7
MC3R represents a therapeutic target for metabolic disorders
PMID: 27288827
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.33Weak
joint diseaseOpen Targets
0.31Weak
crush injuryOpen Targets
0.29Weak
acute tonsillitisOpen Targets
0.24Weak
parasitic infectionOpen Targets
0.24Weak
Obesity due to MC3R deficiencyOpen Targets
0.24Weak
fever of unknown originOpen Targets
0.23Weak
placenta praeviaOpen Targets
0.09Suggestive
acute kidney injuryOpen Targets
0.08Suggestive
Townes-Brocks syndromeOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
candidiasisOpen Targets
0.07Suggestive
obesityOpen Targets
0.07Suggestive
MODYOpen Targets
0.07Suggestive
inherited obesityOpen Targets
0.06Suggestive
obesity due to melanocortin 4 receptor deficiencyOpen Targets
0.06Suggestive
Sertoli Cell-Only SyndromeOpen Targets
0.06Suggestive
metabolic syndromeOpen Targets
0.05Suggestive
metabolic syndrome XOpen Targets
0.05Suggestive
Abnormality of the skeletal systemOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
MODIMELANOTIDEPhase II
Melanocortin receptor 1 agonist
candidiasis
Related Genes
GHRLProtein interaction100%NPYProtein interaction90%ATP7AProtein interaction90%AGRPProtein interaction86%GHSRProtein interaction86%CTSZProtein interaction85%
Tissue Expression6 tissues
Ovary
0%
Bone Marrow
0%
Liver
0%
Brain
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
MC3RGHRLNPYATP7AAGRPGHSRCTSZ
PROTEIN STRUCTURE
Preparing viewer…
PDB8IOC · 2.86 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.20LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.74 [0.47–1.20]
RankingsWhere MC3R stands among ~20K protein-coding genes
  • #4,279of 20,598
    Most Researched111 · top quartile
  • #12,557of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedMC3R
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association between Two Common Missense Substitutions, Thr6Lys and Val81Ile, in MC3R Gene and Childhood Obesity: A Meta-Analysis.
PMID: 29688747
Child Obes · 2018
1.00
2
MC3R links nutritional state to childhood growth and the timing of puberty.
PMID: 34732894
Nature · 2021
0.90
3
Mutations in the melanocortin-3 receptor (MC3R) gene: Impact on human obesity or adiposity.
PMID: 20882712
Curr Opin Investig Drugs · 2010
0.80
4
Understanding the genetic complexity of puberty timing across the allele frequency spectrum.
PMID: 38951643
Nat Genet · 2024
0.70
5
Mutations in Melanocortin-3 Receptor Gene and Human Obesity.
PMID: 27288827
Prog Mol Biol Transl Sci · 2016
0.60