Silencing of JAG2 reduced the cell number by 50–90% in a panel of eight ccRCC cell lines but not in the immortalized embryonic kidney cell line HEK293 (Supporting information, Supplementary Figure 1A); these were efficiently killed by the silencing of PLK1 and UBB (Supporting information, Supplementary Figure 1B), validating our integrative functional genomics approach for therapeutic target identification. Here, JAG2 is linked to nonpapillary renal cell carcinoma.