GLI3 and Pallister-Hall syndrome: It has been proposed that constitutive GLI3R activity is the driver of CAKUT phenotypes in PHS; this notion is supported by the exclusive association of CAKUT with PHS-causing GLI3 variants, as well as the requirement for balanced GLI3A and GLI3R activities in normal kidney formation (31, 44, 45, 51, 79).