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). Here, MAP2K4 is linked to neoplasm.