POMC and Obesity: Collectively, this results in a clinical picture with 1) normal hair pigmentation, reflecting unaffected activation of the MC1R in hair follicles; 2) hypocortisolism with high ACTH, corresponding to a reduced in vitro potency of ACTHKRR at MC2R/MRAP; and 3) obesity and hyperphagia, which are likely explained by the lack of α-MSH and desacetyl-α-MSH to stimulate the MC4R in the hypothalamus, despite normal potency of ACTH at the MC4R and no likely abnormalities in β-melanocortin–stimulating hormone (β-MSH).