While mutations in other metabolic enzymes such as fumarate hydratase and succinate dehydrogenase identified in hereditary leiomyomatosis, renal cell carcinoma and paragangliomas result in loss of function38, IDH1/2 mutations are virtually always heterozygous, suggesting a gain of function as a possible carcinogenic mechanism. Here, FH is linked to hereditary clear cell renal cell carcinoma.