Besides the increased insulin level, blood lipids were comparable in the PRKD2−/− and WT mice (Supplementary Fig. 7a), the body weight of PRKD2−/− mice was significantly increased (Supplementary Fig. 7b), and the insulin-stimulated Akt ser473 phosphorylation in liver (Fig. 4e, f) or skeletal muscle (Fig. 4g, h) was markedly decreased in PRKD2−/− compared with WT mice, indicating the development of obesity and IR. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.