This gene encodes MC3R, a G-protein coupled receptor (GPCR) for melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) that is expressed in the brain. This gene maps to the same region as the locus for benign neonatal epilepsy. Mice deficient for this gene have increased fat mass, reduced lean mass and decreased food intake, all suggesting a role for the receptor in the regulation of energy homeostasis.[6]MC3R mutations has been linked to reduced growth rate during childhood and a delay in the age of puberty onset.[7]
Studies performed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), found that two specific polymorphisms in the MC3R gene may be associated with pediatric obesity and greater body mass because of greater energy intake. Children who were homozygous for C17A + G241A consumed approximately 38% more than those who did not contain aforementioned polymorphisms. The study concluded that these genetic variants did not affect energy expenditure.[8]
^Lam, B.Y.H., Williamson, A., Finer, S. et al. MC3R links nutritional state to childhood growth and the timing of puberty. Nature (2021). doi:10.1038/s41586-021-04088-9
^Cai M, Mayorov AV, Ying J, Stankova M, Trivedi D, Cabello C, Hruby VJ (August 2005). "Design of novel melanotropin agonists and antagonists with high potency and selectivity for human melanocortin receptors". Peptides. 26 (8): 1481–1485. doi:10.1016/j.peptides.2005.03.020. PMID15876475. S2CID45499654.
Magenis RE, Smith L, Nadeau JH, Johnson KR, Mountjoy KG, Cone RD (August 1994). "Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human". Mammalian Genome. 5 (8): 503–8. doi:10.1007/BF00369320. PMID7949735. S2CID24047677.
Tota MR, Smith TS, Mao C, MacNeil T, Mosley RT, Van der Ploeg LH, Fong TM (January 1999). "Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors". Biochemistry. 38 (3): 897–904. doi:10.1021/bi9815602. PMID9893984.
McNulty JC, Thompson DA, Bolin KA, Wilken J, Barsh GS, Millhauser GL (December 2001). "High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein". Biochemistry. 40 (51): 15520–7. doi:10.1021/bi0117192. PMID11747427.
Wong J, Love DR, Kyle C, Daniels A, White M, Stewart AW, Schnell AH, Elston RC, Holdaway IM, Mountjoy KG (October 2002). "Melanocortin-3 receptor gene variants in a Maori kindred with obesity and early onset type 2 diabetes". Diabetes Research and Clinical Practice. 58 (1): 61–71. doi:10.1016/S0168-8227(02)00126-2. PMID12161058.
Lapinsh M, Veiksina S, Uhlén S, Petrovska R, Mutule I, Mutulis F, Yahorava S, Prusis P, Wikberg JE (January 2005). "Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes". Molecular Pharmacology. 67 (1): 50–9. doi:10.1124/mol.104.002857. PMID15470082. S2CID13536417.
Mandrika I, Petrovska R, Wikberg J (January 2005). "Melanocortin receptors form constitutive homo- and heterodimers". Biochemical and Biophysical Research Communications. 326 (2): 349–54. doi:10.1016/j.bbrc.2004.11.036. PMID15582585.
de Krom M, de Rijke CE, Hendriks J, van Engeland H, van Elburg AA, Adan RA (December 2005). "Mutation analysis of the agouti related protein promoter region and the melanocortin-3 receptor in anorexia nervosa patients". Psychiatric Genetics. 15 (4): 237. doi:10.1097/00041444-200512000-00003. PMID16314751.
Chen M, Aprahamian CJ, Celik A, Georgeson KE, Garvey WT, Harmon CM, Yang Y (January 2006). "Molecular characterization of human melanocortin-3 receptor ligand-receptor interaction". Biochemistry. 45 (4): 1128–37. doi:10.1021/bi0521792. PMID16430209.
