Although the SETD2 mutation rate in HCC patients is only ~5%, SETD2 mutations in the liver are associated with the occurrence of spontaneous HCC and the progression of HCC induced by DEN and a high-fat diet in vivo; animal experiments revealed that SETD2 represses HCC tumorigenesis by maintaining lipid homeostasis and that SETD2 deficiency causes abnormal expression of cholesterol metabolism genes and lipid accumulation; these increases in lipid levels activate c-Jun, inhibit p53 activation and induce HCC 14. The gene discussed is JUN; the disease is hepatocellular carcinoma.