We identified 2 novel variants in the adenylate cyclase 3 gene (ADCY3): a homozygous frameshift variant, c.2520C>G p.Thr840X, in a 4-year-old girl born to a consanguineous Pakistani parents who presented with severe obesity and signs of insulin resistance. Here, ADCY3 is linked to obesity due to melanocortin 4 receptor deficiency.