Obesity‐associated mutant melanocortin‐4 receptors with normal Gα_s coupling frequently exhibit other discoverable pharmacological and biochemical defects

Mutations in the melanocortin-4 receptor (MC4R) are the most common cause of early syndromic obesity known. Most of these mutations result in a loss of protein expression, α-melanocyte-stimulating hormone binding, receptor trafficking or coupling to the stimulatory G-protein, Gαs . However, approximately 26% of the obesity-associated mutations characterised to date exhibit none of these pharmacological defects. In the present study, we...