MC4R and obesity due to melanocortin 4 receptor deficiency: Haploinsufficiency of Sim1 is associated with hyperphagic obesity and increased linear growth (Kublaoui et al., 2006; Michaud et al., 2001) closely resembling the phenotype of agouti yellow (Ay), and Mc4r null mice, two classic models of disrupted hypothalamic melanocortin signaling.