It was reported that ccRCC was characterized by loss of function of the tumor suppressor VHL and activation of hypoxia-inducible transcription factors (HIFs), and the VHL gene product (pVHL) targeted HIFs transcription factors for proteasomal degradation, and then increased HIF2a promotes pVHL-defective tumorigenesis 11-13. Here, EPAS1 is linked to nonpapillary renal cell carcinoma.