Loss-of-function mutations in VHL, which encodes the tumor suppressor pVHL, cause VHL disease, an autosomal dominant cancer disorder with predisposition to central nervous system hemangioblastoma, PPGL, and clear cell renal cell carcinoma (ccRCC) as well as polycythemia, and the majority of sporadic cases of hemangioblastoma and ccRCC44. This evidence concerns the gene VHL and clear cell renal carcinoma.