EPAS1 and clear cell renal carcinoma: Moreover, the carcinogenic potential of metal ions, such as Cd, in the kidney (Hartwig 2013), may be accelerated by activation of HPHE signaling, as exemplified by the proposed role of HIF2A in promoting clear cell renal cell carcinoma (Choueiri et al. 2021; Dufies et al. 2021).