SH2B1 is a strong prior candidate for regulating body weight; it is implicated in leptin signaling; Sh2b1-null mice are obese; and the evidence suggests that the effects of this gene on obesity are mediated through the central nervous system [173] (see Leptin, hypothalamus and AIS). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.