MC4R and obesity disorder: Besides SIM1 and MC4R, the haploinsufficiency of proprotein convertase 1 (PCSK1), melanocortin 2 receptor accessory protein 2 (MRAP2) in the brain, iroquois homeobox 3 (IRX3) in fat or uncoupling protein 3 (UCP3) in mitochondria are also responsible for human obesity (Argyropoulos et al., 1998; Creemers et al., 2012; Asai et al., 2013; Zou et al., 2017).