MC4R and obesity due to melanocortin 4 receptor deficiency: Functional defects resulting from mutations in the MC4R gene that are responsible for obesity include decreased or absent ligand binding; decreased cell surface receptor expression (because of intracellular retention of mutant receptors); incorrect protein folding (which results in the receptor not being released from the endoplasmic reticulum); and reduced signal transduction (Tao and Segaloff 2005; Chen et al.