MC4R

About MC4R

MC4R on chromosome 18q21.32 encodes the melanocortin 4 receptor, a G protein coupled receptor in the hypothalamus that is a key part of the leptin melanocortin pathway controlling appetite and energy balance. Leptin from fat tissue stimulates neurons that release alpha melanocyte stimulating hormone, which activates MC4R and signals fullness. Loss of function variants in MC4R are the most common known cause of monogenic obesity, typically producing severe early onset obesity with intense hunger, increased linear growth, and increased lean mass. Most carriers have one affected copy, and the effect can vary. More common variants near the gene contribute modestly to obesity risk in the general population, while some gain of function variants are associated with lower body weight. Setmelanotide, an MC4R agonist, is approved for certain rare genetic obesity disorders affecting the pathway upstream of the receptor.