{"entity":{"id":"aldh2","kind":"target","name":"ALDH2","aka":["aldehyde dehydrogenase 2 family member","Aldehyde dehydrogenase, mitochondrial"],"tldr":"ALDH2 (Aldehyde dehydrogenase, mitochondrial) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target and an oncogene driver, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Osteosarcoma.","summary":"Mitochondrial aldehyde dehydrogenase with broad substrate specificity which participates in the detoxification of ethanol-derived acetaldehyde and endogenous aldehydes, including those arising from lipid peroxidation. The reaction mechanism involves a nucleophilic attack on the aldehyde substrate, resulting in formation of a thiohemiacetal intermediate. Subsequent hydride transfer to NAD+, yields a thioester intermediate which is hydrolysed to the carboxylic acid product through activation of a water molecule by the catalytic glutamate.\n\nOpen Targets scores its association with cancer at 0.58 (direct and indirect evidence; datatypes clinical 0.42, literature 0.99, genetic association 0.61, somatic mutation 0.43, animal model 0.52). IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Osteosarcoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:404","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:404"},{"label":"UniProt P05091","url":"https://www.uniprot.org/uniprotkb/P05091/entry"},{"label":"NCBI Gene 217","url":"https://www.ncbi.nlm.nih.gov/gene/217"},{"label":"Ensembl ENSG00000111275","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000111275"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["osteosarcoma"],"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: Open Targets known-drug datatype score 0.42; IntOGen calls it an activating (Act) driver in 1 cohort. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"ALDH2","role":["drug-target","oncogene-driver"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:404","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:404","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P05091","url":"https://www.uniprot.org/uniprotkb/P05091/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000111275","url":"https://platform.opentargets.org/target/ENSG00000111275/associations","note":"association with cancer (MONDO_0004992) 0.58;  (GraphQL API, CC0)"},{"label":"IntOGen ALDH2","url":"https://www.intogen.org/search?gene=ALDH2","note":"driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"one-type","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 ALDH2: RNA tissue enhanced (liver 801 nTPM); blood lineage group enriched (dendritic cells 214 nTPM, monocytes 213 nTPM); high antibody staining in 3 normal tissues; highest cancer staining melanoma (1 of 10 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P05091","url":"https://www.uniprot.org/uniprotkb/P05091/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen ALDH2","url":"https://www.intogen.org/search?gene=ALDH2","note":"driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas ALDH2 tissue","url":"https://www.proteinatlas.org/ENSG00000111275-ALDH2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000111275 associations","url":"https://platform.opentargets.org/target/ENSG00000111275/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:404","ensembl":"ENSG00000111275","uniprot":"P05091","entrez":"217","firstDescribed":1985,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Hempel et al, Eur. J. Biochem, 1985, \"Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/4065146/","biology":"Mitochondrial aldehyde dehydrogenase with broad substrate specificity which participates in the detoxification of ethanol-derived acetaldehyde and endogenous aldehydes, including those arising from lipid peroxidation. The reaction mechanism involves a nucleophilic attack on the aldehyde substrate, resulting in formation of a thiohemiacetal intermediate. Subsequent hydride transfer to NAD+, yields a thioester intermediate which is hydrolysed to the carboxylic acid product through activation of a water molecule by the catalytic glutamate. In vivo, ALDH2 is required for the clearance of formaldehyde, a cytotoxic and carcinogenic endogenous metabolite that induces DNA damage. It also catalyses the oxidation of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a reactive intermediate of dopamine catabolism, to 3,4-dihydroxyphenylacetate (DOPAC). ALDH2 may also catalyse the oxidation of 4-aminobutanal (gamma-aminobutyraldehyde) to 4-aminobutanoate (GABA), representing an alternative route for GABA biosynthesis from polyamine catabolism. Location: Mitochondrion (UniProt). Locus 12q24.12 (HGNC).","whereFound":["Osteosarcoma: IntOGen driver in 1 cohort (OS)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/aldh2/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"}]}}