Our data firmly support the involvement of PDZ-RhoGEF in the genetics of fat mass regulation and predisposition to obesity and T2D, previously suggested by the association of the PDZ-RhoGEF SNP R1467H with the epidemiology of T2D (Bottcher et al., 2008; Fu et al., 2007; Jin et al., 2010; Liu et al., 2011; Ma et al., 2007). This evidence concerns the gene ARHGEF11 and obesity due to melanocortin 4 receptor deficiency.