MC4R and Obesity: Monogenic mutation is relatively rare and primarily affects the genes involved in the leptin–melanocortin pathway, the central regulator of food intake and energy balance (Oussaada et al., 2019); as examples, the leptin receptor (LEPR) (Farooqi et al., 2007), pro-opiomelanocortin (POMC) (Krude et al., 2003), melanocortin 4 receptor (MC4R) (Krude et al., 2003), and MC3R (Lee et al., 2002) have all been linked to early onset of obesity in humans.