MC4R and obesity due to melanocortin 4 receptor deficiency: Nine residues in the intracellular region were selected, seven of which were reported in individuals that were obese or overweight, although all were functionally characterized previously as WT-like or to increase MC4R-induced cAMP signaling [22], inconsistent with MC4R loss-of-function usually observed in obesity [9] (Tables 1 and 2).