In summary, we have identified a gene involved in CKD by positional cloning and established a potential mechanism supporting the functional significance of genetic variants in Arhgef11 in promoting changes in cell morphology (Rho-Rock and/or EMT) and function of tubule cells that works in concert with other susceptibility factors (e.g. TGFβ-1) to promote progressive decline in kidney function. Here, TGFB1 is linked to chronic kidney disease.