Since the suppression of PBRM1, KDM5C, SETD2 or BAP1 all lead to the reduction of ISGF3, a potent tumor suppressor, it is possible that any effective therapeutic intervention that restores ISGF3 function could benefit ccRCC patients with a wide variety of mutations. Here, KDM5C is linked to nonpapillary renal cell carcinoma.