{"entity":{"id":"fh","kind":"target","name":"FH","aka":["fumarate hydratase","Fumarate hydratase, mitochondrial"],"tldr":"FH (Fumarate hydratase, mitochondrial) is an enzyme. The public catalogues list it as a drug target, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Neuroendocrine tumours, Skin cancer, Papillary renal cell carcinoma and 1 more.","summary":"Catalyses the reversible stereospecific interconversion of fumarate to L-malate. Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other. Catalyses the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Erlotinib and Bevacizumab. Open Targets scores its association with cancer at 0.76 (direct and indirect evidence; datatypes literature 0.99, genetic association 0.67, somatic mutation 0.95, genetic literature 0.85).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:3700","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3700"},{"label":"UniProt P07954","url":"https://www.uniprot.org/uniprotkb/P07954/entry"},{"label":"NCBI Gene 2271","url":"https://www.ncbi.nlm.nih.gov/gene/2271"},{"label":"Ensembl ENSG00000091483","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000091483"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets"],"cancers":["neuroendocrine","skin-cancer","papillary-rcc","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; CIViC holds 2 clinical evidence items on its variants; UniProt keyword \"DNA repair\". Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Hereditary Renal Cell Carcinoma."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"FH","role":["drug-target","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:3700","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3700","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P07954","url":"https://www.uniprot.org/uniprotkb/P07954/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene FH","url":"https://civicdb.org/features/1892","note":"2 evidence items, 0 assertions, 2 variants; diseases: Papillary Renal Cell Carcinoma, Hereditary Renal Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000091483","url":"https://platform.opentargets.org/target/ENSG00000091483/associations","note":"association with cancer (MONDO_0004992) 0.76; per-cancer scores at or above 0.5: melanoma 0.51, neuroendocrine neoplasm 0.54, skin cancer 0.51 (GraphQL API, CC0)"}],"hgnc":"HGNC:3700","ensembl":"ENSG00000091483","uniprot":"P07954","entrez":"2271","biology":"Catalyses the reversible stereospecific interconversion of fumarate to L-malate. Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other. Catalyses the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH. Catalyses the dehydration of L-malate to fumarate. Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism. Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ). Location: Mitochondrion; Cytoplasm, cytosol; Nucleus; Chromosome (UniProt). Locus 1q43 (HGNC).","whereFound":["Neuroendocrine tumours: Open Targets association 0.54 with neuroendocrine neoplasm (MONDO_0019496)","Skin cancer: Open Targets association 0.51 with skin cancer (MONDO_0002898)","Papillary renal cell carcinoma: CIViC evidence names this disease","Melanoma: Open Targets association 0.51 with melanoma (MONDO_0005105)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/fh/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}