In a disease setting, inactivating mutations in the enzyme fumarate hydratase (FH) or subunits of succinate dehydrogenase (SDH) or its assembly factors (SDHAF1, 2) are causative for certain rare tumour syndromes [145–147] in which constitutive HIF stabilisation is detectable and is thought to contribute to disease progression [148]. This evidence concerns the gene FH and neoplasm.