SIM2 and obesity due to melanocortin 4 receptor deficiency: Sim plays an important role in the differentiation of central nervous system (CNS) midline cells within the ventral neurogenic region in Drosophila. 57 In mice, Sim1 heterozygousity leads to early-onset obesity, with increased linear growth, hyperinsulinemia, and hyperleptinemia,58 while haploinsufficiency of SIM1 has been reported to cause severe early-onset human obesity due to a balanced translocation between chromosomes 1p22.1 and 6q16.2.59