Its deletion provokes metabolic disorders in SH2B1 KO mice, including leptin resistance, obesity, and glucose intolerance whereas restoration of SH2B1 corrected these metabolic disturbances and improved JAK2-mediated leptin signaling and regulation of hypothalamic orexigenic neuropeptides [95]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.