The intronic location of common SNPs associated with BMI and obesity within a 47 kb region that covers parts of the first two introns and exon 2 of FTO [1] indicates that the amino acid sequence of FTO protein does not exert its effects through functional mutations, and is more likely to play a role in transcription regulation through its effect on the expression of FTO gene and/or neighboring genes, such as the IRX3/IRX5 genes, specifically in adipocytes. This evidence concerns the gene IRX3 and obesity due to melanocortin 4 receptor deficiency.