SETD2 and nonpapillary renal cell carcinoma: As mentioned before, SETD2 trimethylates actin (ActK68me3), cells lacking SETD2 have decreased interaction of the actin nucleation-promoting factor WHAMM with its target actin, actin filaments are required for initiation of autophagy in ccRCC, and autophagy markers LC3-II and p62 are decreased (44).