Mutations in genes that have a physiological role in the hypothalamic leptin–melanocortin energy balance system, such as mutations in leptin, leptin receptor, POMC, prohormone 1/3 convertases (PC1/3), MC4R, are related to the currently known monogenic forms of obesity (Figure 1). Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.