The VHL-defective lesions arising in the kidneys of VHL patients demonstrate an increase in HIF and HIF target genes, and mouse VHL–/– ccRCC xenograft experiments revealed a tumor-promoting role of HIF2α and a tumor-constraining role of HIF1α (Kaelin, 2022). The gene discussed is EPAS1; the disease is nonpapillary renal cell carcinoma.