{"entity":{"id":"sdha","kind":"target","name":"SDHA","aka":["succinate dehydrogenase complex flavoprotein subunit A","Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial","SDH2"],"tldr":"SDHA (Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Neuroendocrine tumours, Renal cell carcinoma, Hepatocellular carcinoma and 5 more.","summary":"Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDH also oxidises malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate. Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerised into keto-oxaloacetate.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.84 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.81, somatic mutation 0.86, genetic literature 0.81). IntOGen calls it a driver in 3 cohorts (2 activating, 0 loss-of-function), covering Chromophobe Renal Cell Carcinoma, Hepatocellular Carcinoma, Low-Grade Glioma, NOS.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:10680","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10680"},{"label":"UniProt P31040","url":"https://www.uniprot.org/uniprotkb/P31040/entry"},{"label":"NCBI Gene 6389","url":"https://www.ncbi.nlm.nih.gov/gene/6389"},{"label":"Ensembl ENSG00000073578","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000073578"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["neuroendocrine","rcc","hcc","lung-cancer","sarcoma","colorectal","ovarian","gist"],"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: IntOGen calls it an activating (Act) driver in 2 cohorts; CIViC holds 1 clinical evidence items on its variants. 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: Adrenal Gland Pheochromocytoma; Low-Grade Glioma, NOS."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SDHA","role":["oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:10680","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10680","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P31040","url":"https://www.uniprot.org/uniprotkb/P31040/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SDHA","url":"https://civicdb.org/features/5176","note":"1 evidence items, 0 assertions, 2 variants; diseases: Adrenal Gland Pheochromocytoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000073578","url":"https://platform.opentargets.org/target/ENSG00000073578/associations","note":"association with cancer (MONDO_0004992) 0.84; per-cancer scores at or above 0.5: colorectal cancer 0.51, ovarian cancer 0.50, sarcoma 0.52, neuroendocrine neoplasm 0.84, gastrointestinal stromal tumour 0.74, lung cancer 0.52 (GraphQL API, CC0)"},{"label":"IntOGen SDHA","url":"https://www.intogen.org/search?gene=SDHA","note":"driver in 3 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA SDHA: RNA tissue enhanced (heart muscle 522 nTPM, skeletal muscle 447 nTPM); high antibody staining in 15 normal tissues; highest cancer staining liver cancer (4 of 12 high). Distribution: 7 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Neuroendocrine tumours, Renal cell carcinoma, Hepatocellular carcinoma, Lung cancer (all types), Sarcomas (soft tissue, bone, GIST), Colorectal cancer, Ovarian cancer); Open Targets associates it with 4 specific cancer types at or above 0.5 (pheochromocytoma/paraganglioma syndrome 5, gastrointestinal stromal tumor, hereditary pheochromocytoma-paraganglioma, hereditary neoplastic syndrome). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P31040","url":"https://www.uniprot.org/uniprotkb/P31040/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SDHA","url":"https://civicdb.org/features/5176","note":"1 evidence items, 0 assertions, 2 variants; diseases: Adrenal Gland Pheochromocytoma (GraphQL API, CC0)"},{"label":"IntOGen SDHA","url":"https://www.intogen.org/search?gene=SDHA","note":"driver in 3 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas SDHA tissue","url":"https://www.proteinatlas.org/ENSG00000073578-SDHA/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000073578 associations","url":"https://platform.opentargets.org/target/ENSG00000073578/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:10680","ensembl":"ENSG00000073578","uniprot":"P31040","entrez":"6389","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Malcovati et al, 1991, \"Cloning of the flavoprotein subunit of human succinate dehydrogenase\".","firstDescribedSource":"https://www.uniprot.org/uniprotkb/P31040/entry","biology":"Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDH also oxidises malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate. Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerised into keto-oxaloacetate. Can act as a tumour suppressor. Location: Mitochondrion inner membrane (UniProt). Locus 5p15.33 (HGNC).","whereFound":["Neuroendocrine tumours: Open Targets association 0.84 with neuroendocrine neoplasm (MONDO_0019496)","Renal cell carcinoma: IntOGen driver in 1 cohort (CHRCC)","Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)","Lung cancer: Open Targets association 0.52 with lung cancer (MONDO_0008903)","Sarcomas: Open Targets association 0.52 with sarcoma (MONDO_0005089)","Colorectal cancer: Open Targets association 0.51 with colorectal cancer (MONDO_0005575)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/sdha/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","route":"/cancers/gist/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}]}}