Intriguingly, in human brains, obesity associated SNPs within FTO are functionally connected, at megabase distances, with regulation of the homeobox gene IRX3 expression, but not FTO, and in vivo studies in mice demonstrated that the expression levels of IRX3 affect body mass and composition phenotypes, suggesting that although the obesity associated SNPs reside in the first intron of FTO gene, they may not only influence FTO but mediate their obesity effects through long-range interaction with nearby genes (notably IRX3 and RPGRIP1L) [22]. This evidence concerns the gene RPGRIP1L and obesity due to melanocortin 4 receptor deficiency.