In an additional VHL-knockout mouse model, we found that the risk of renal cyst formation, which is a precursor to clear cell renal cell carcinoma (ccRCC), depends on HIF-2α rather than HIF-1α, emphasizing the importance of HIF-2α as a cancerigenic factor (Rankin et al., 2006). The gene discussed is EPAS1; the disease is nonpapillary renal cell carcinoma.