MC3R and obesity due to melanocortin 4 receptor deficiency: Even though there is no clear evidence that heterozygous variants in MC3R cause severe monogenic obesity, there are some isolated cases which reported that heterozygous MC3R variants are associated to severe obesity; for instance, Lee et al reported a heterozygous missense MC3R variant paternally inherited in a severely obese patient and her father with early-onset obesity at the age of 5 years (21).