Somatic and epigenetic mutations of the von Hippel-Lindau (VHL) disease tumor suppressor gene are observed in 42-57% and 5-19% of sporadic clear cell RCCs, respectively.[5] In normoxic cells, hypoxia-inducible factor 1α (HIF-1α) is hydroxylated by specific prolyl hydroxylases, leading to recognition and binding by the VHL gene protein (pVHL) and targeting for ubiquitination and rapid degradation through the proteosome.[6] Under hypoxic conditions, HIF-1α is not hydroxylated and does not bind to pVHL, which leads to HIF-1α protein stabilization and translocation to the nucleus. The gene discussed is VHL; the disease is neoplasm.