Melanocortin 4 receptor

Melanocortin receptor 4 is a is_associated_with::protein that in humans is encoded by the MC4R is_associated_with::gene. It encodes the MC4 protein, a is_associated_with::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.

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 is_associated_with::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.

Interactions
Melanocortin 4 receptor has been shown to interact with is_associated_with::proopiomelanocortin.

Clinical significance
In 2009, two very large is_associated_with::genome-wide association studies of is_associated_with::body mass index (BMI) confirmed the association of variants about 150 kilobases downstream of the MC4R gene with insulin resistance, is_associated_with::obesity, and other anthropometric traits. MC4R may also have clinical utility as a is_associated_with::biomarker for predicting individual susceptibility to drug-induced is_associated_with::adverse effects causing is_associated_with::weight gain and related metabolic abnormalities. Another GWAS performed in 2012 identified twenty is_associated_with::SNPs located ~190 Kb downstream of MC4R in association with severe is_associated_with::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.

Non-selective

 * α-MSH
 * β-MSH
 * γ-MSH
 * ACTH
 * is_associated_with::Afamelanotide
 * is_associated_with::Bremelanotide
 * is_associated_with::Melanotan II
 * is_associated_with::Modimelanotide
 * is_associated_with::Setmelanotide

Selective

 * is_associated_with::AZD2820
 * is_associated_with::LY-2112688
 * is_associated_with::MK-0493
 * is_associated_with::PF-00446687
 * is_associated_with::PG-931
 * is_associated_with::PL-6983
 * is_associated_with::Ro 27-3225 – also some activity at MC1
 * is_associated_with::THIQ

Non-selective

 * is_associated_with::Agouti-related peptide
 * is_associated_with::Agouti signalling peptide
 * is_associated_with::SHU-8914
 * is_associated_with::SHU-9005
 * is_associated_with::SHU-9119

Selective

 * is_associated_with::HS-014
 * is_associated_with::HS-024
 * is_associated_with::JKC-363
 * is_associated_with::MCL-0020
 * is_associated_with::MCL-0042 – also a is_associated_with::serotonin reuptake inhibitor
 * is_associated_with::MCL-0129
 * is_associated_with::ML-00253764
 * is_associated_with::MPB-10

Unknown

 * is_associated_with::Semax