HIF-dependent effects on c-Myc can be used to classify pVHL-defective ccRCC into two subtypes – HIF-2α-expressing subtype (displaying increased c-Myc activity and faster proliferation) and HIF-1α/2α-expressing subtype (displaying neither enhanced nor diminished c-Myc activity due to HIF-1α/2α antagonism) [162]. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.