Protein / target
Melanocortin receptor 4
Protein at a glance
Biological role
Melanocyte-stimulating hormone receptor activity
Primary system
Nervous system
Strongest disease association
Abnormality of the skeletal system
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
4 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha- and beta-MSH) and corticotropin/ACTH, which are peptide products of the POMC precursor (PubMed:12646665, PubMed:14764818, PubMed:25163632, PubMed:32327598, PubMed:33858992, PubMed:8392067). Functions as a central component of the leptin-melanocortin pathway, which is essential for maintaining energy homeostasis (PubMed:32327598, PubMed:33858992). Upon activation, couples to G(s) protein, stimulating adenylate cyclase and the cAMP-dependent signaling pathway, which promotes anorexogenic signaling in the hypothalamus and contributes to a negative energy balance (PubMed:12588803, PubMed:14764818, PubMed:25163632, PubMed:33858992). Regulates food intake: activation by agonists suppresses appetite, whereas the antagonist Agouti-related protein/AGRP precludes agonist-induced signaling, thereby stimulating appetite (PubMed:9311920, PubMed:29311635). Modulates the firing activity of neurons in paraventricular nucleus (PVN) of the hypothalamus via alpha-MSH and AGRP regulation of inwardly rectifying potassium channel KCNJ13 closure, independently of G(s) signaling (PubMed:32327598). In the PVN, also interacts with opsin 3/OPN3, which couples to G(i/o) proteins to inhibit MC4R-mediated cAMP signaling, thereby promoting food intake (PubMed:39951488). In intestinal epithelial cells, contributes to inhibition of hepatic glucose production via nesfatin-1/NUCB2, leading to increased cAMP levels and glucagon-like peptide 1 (GLP-1) secretion (PubMed:39562740). Interaction with MGRN1 displaces the G(s) protein, further decreasing MC4R signaling activity (PubMed:19737927). Also activated by gamma-MSH, though with low potency (PubMed:8392067)
Subcellular location
Domains and Gene Ontology detail (18)Hide
Gene Ontology
- Ccytoplasm
- Cmembrane
- Cnon-motile cilium membrane
- Cplasma membrane
- Fcorticotropin receptor activity
- Fmelanocortin receptor activity
- Fmelanocyte-stimulating hormone receptor activity
- Fneuropeptide binding
- Fubiquitin protein ligase binding
- Padenylate cyclase-activating G protein-coupled receptor signaling pathway
- Padenylate cyclase-modulating G protein-coupled receptor signaling pathway
- Pfeeding behavior
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
G protein-coupled signalling
- ·G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha- and beta-M…
- ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
- ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
Transcriptional regulation
- ·Transcriptional and post-translational regulation of MITF-M expression and activity
View underlying pathways (3)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Melanocortin receptor 4 agonist
Appears in clinical studies involving obesity disorder, Obesity, Bardet-Biedl syndrome, Bardet-Biedl syndrome
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 636 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 5 total
erectile dysfunction · sexual dysfunction · sexual dysfunction
mental disorder · sexual dysfunction · physiological sexual disorder
obesity disorder
obesity disorder · Obesity · Bardet-Biedl syndrome
sexual dysfunction · erectile dysfunction
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (16)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationLead-in calorie restriction enhances the weight-lowering efficacy of incretin hormone-based pharmacotherapies in mice.
- Regulatory approval
Approval: Imcivree (EMA)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.