Among the wide spectrum of mutants, they only obtained Pbx1−/−, Pbx2+/−, and Pbx1−/−; Pbx3+/− presented fully penetrant CLP with hypoplasia of the jaw; Pbx1+/−, Pbx2+/−, and Pbx3+/− mutants died at birth presenting isolated CP; and Pbx1-specific deactivation within surface cephalic ectoderm and on Pbx2- or Pbx3-deficient background resulted in orofacial clefting. The gene discussed is PBX2; the disease is orofacial cleft.