MC4R and obesity due to melanocortin 4 receptor deficiency: Similarly, variants in appetite-regulating genes including, the melanocortin 4 receptor (MC4R) and fat mass and obesity-associated gene (FTO), may enhance susceptibility to weight gain under high-energy diets (26, 27), whereas sex-specific genetic effects [e.g., in ANK4 or ankyrin 1 (ANK1)] can lead to divergent dietary responses between males and females (28).