We report on the novel gain-of-function GCK variant p.Val455Leu (V455L), inherited as an autosomal dominant trait in a German family with CHI and concomitant obesity (fasting blood glucose 2.1 mmol/l, BMI 45.0 kg/m2, HOMA-IR 1.5 in an adult female family member); one male family member developed type 2 diabetes until age 35 years (with fasting glucose 2.8–3.7 mmol/l, BMI 38.9 kg/m2, HOMA-IR 4.6). This evidence concerns the gene GCK and obesity due to melanocortin 4 receptor deficiency.