Melanocortin 4 receptor

Updated on Oct 27, 2023

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Species Human Entrez 4160		Human Mouse Ensembl ENSG00000166603

Aliases MC4R, Melanocortin 4 receptor External IDs MGI: 99457 HomoloGene: 4320 GeneCards: MC4R

Gene music using protein sequence of mc4r melanocortin 4 receptor

Melanocortin 4 receptor is a protein that in humans is encoded by the MC4R gene. It encodes the MC₄ protein, a G protein-coupled receptor that binds α-melanocyte stimulating hormone (α-MSH). In murine models MC₄ receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function.

Melanocortin 4 receptor Figure 4 Neuropeptide gene polymorphisms and human behavioural

In 2008, MC4R mutations were reported to be associated with inherited human obesity. They were found in heterozygotes, suggesting an autosomal dominant inheritance pattern. However, based on other research and observations, these mutations seem to have an incomplete penetrance and some degree of codominance. It has a prevalence of 1.0-2.5% in people with body mass indices greater than 30, making it the most commonly known genetic defect predisposing people to obesity.

Melanocortin 4 receptor 2iqv Melanocortin4 receptor model inactive state with

Clinical significance

Melanocortin 4 receptor 2iqr Melanocortin4 receptor model active state with agonist NDP

In 2009, two very large genome-wide association studies of body mass index (BMI) confirmed the association of variants about 150 kilobases downstream of the MC4R gene with insulin resistance, obesity, and other anthropometric traits. MC4R may also have clinical utility as a biomarker for predicting individual susceptibility to drug-induced adverse effects causing weight gain and related metabolic abnormalities. Another GWAS performed in 2012 identified twenty SNPs located ~190 Kb downstream of MC4R in association with severe antipsychotic-induced weight gain. This locus overlapped with the region previously identified in the 2009 studies. The rs489693 polymorphism, in particular, sustained a statistically robust signal across three replication cohorts and demonstrated consistent recessive effects. This finding was replicated again by another research group in the following year. In accordance with the above, MC₄ receptor agonists have garnered interest as potential treatments for obesity and insulin resistance, while MC₄ receptor antagonists have attracted interest as potential treatments for cachexia.

Melanocortin 4 receptor The Neurocritic The Joy of Melanocortin Receptors

MC₄ receptor agonists like bremelanotide (PT-141), PL-6983, and PF-00446687 are under investigation as powerful potential treatments for both female and male sexual dysfunction, including hypoactive sexual desire disorder and erectile dysfunction. Bremelanotide and melanotan II are already used for sexual enhancement by the general population via their accessibility due to online drug vendors. The non-selective melanocortin receptor agonist afamelanotide (NDP-α-MSH) has been found to induce brain-derived neurotrophic factor (BDNF) expression in the rodent brain via activation of the MC₄ receptor and mediate "intense" neurogenesis and cognitive recovery in an animal model of Alzheimer's disease. MC₄ receptor antagonists produce pronounced antidepressant- and anxiolytic-like effects in animal models of depression and anxiety. And agonists of the MC₄ receptor such as melanotan II and PF-00446687, via activation of the central oxytocin system, have been found to promote pair bond formation in prairie voles and, due to these prosocial effects, have been suggested as possible treatments for social deficits in autism spectrum disorders and schizophrenia.