If pVHL is mutated, as in ccRCC, binding of HIF-1α by pVHL does not occur; the unbound HIF1α is not degraded, but associates with the constitutively stable partner HIF-1β to form an active heterodimeric HIF-1 transcription factor, which binds to hypoxia-responsive elements located in the promoter/enhancer regions of numerous hypoxia-inducible genes. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.