HIF-2α-dependent sensitivity to ferroptosis was also observed in ccRCC cells expressing individual HIF-2α-targeting sgRNAs and shRNAs, in single-cell EPAS1−/− clones with or without restored EPAS1-GFP expression, as well as HIF-2α/GPX4 double knockouts (Fig. 2d–h, Supplementary Fig. 4a–f and Supplementary Data 8). This evidence concerns the gene GPX4 and nonpapillary renal cell carcinoma.