The HIF signaling pathway is activated not only by hypoxia but also by mutations that inactivate tumor suppressor genes such as VHL. Loss of function of the VHL protein causes an autosomal dominant hereditary disorder characterized by clear cell renal carcinoma, retinal, cerebellar and spinal hemangioblastoma and a multitude of visceral tumors. The gene discussed is VHL; the disease is Spinal hemangioblastoma.