For example, the loss-of-function of VHL by genetic alteration results in the constitutive expression of HIF-1α and in onset of VHL disease, a dominantly inherited familial cancer syndrome characterized by susceptibility to retinal and central nervous system haemangioblastomas, clear cell renal cell carcinomas, pheochromocytoma, pancreatic islet cell tumours and renal, pancreatic and epididymal cysts63, 64. Here, HIF1A is linked to hereditary pheochromocytoma-paraganglioma.