In studies of 777 people with MC4R deficiency (the largest cohort reported to date), we found that the severity of obesity is influenced by gene dosage, because people with biallelic mutations have a higher BMI and BMI SDS than those with monoallelic or heterozygous mutations (Fig. 2a) and that penetrance is highly variable. This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.