MAP2K4 and cancer: Confirmation of the MKK4 gene as a tumor suppressor has been obtained from different cancer cell lines in which, loss of heterozygosity (LOH) or presence of missense variants, produce a loss of function of MKK4 (23, 27, 34).This loss of function due to mutations or decreased expression of MKK4 has been described in patients with biliary cancer (42).