{"entity":{"id":"ercc2","kind":"target","name":"ERCC2","aka":["ERCC excision repair 2, TFIIH core complex helicase subunit","General transcription and DNA repair factor IIH helicase subunit XPD","EM9","MGC102762","MGC126218","MGC126219"],"tldr":"ERCC2 (General transcription and DNA repair factor IIH helicase subunit XPD) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Bladder & urothelial cancer, Skin cancer, Colorectal cancer and 5 more.","summary":"ATP-dependent 5'-3' DNA helicase. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, not absolutely essential for minimal transcription in vitro. Required for transcription-coupled nucleotide excision repair (NER) of damaged DNA; recognises damaged bases.\n\nCIViC holds 23 clinical evidence items and 0 assertions across 15 variants, naming Chemotherapy, Immune Checkpoint Inhibitor, Paclitaxel and Carboplatin and others. Open Targets scores its association with cancer at 0.83 (direct and indirect evidence; datatypes genetic literature 0.30, affected pathway 0.61, literature 0.99, genetic association 0.62, somatic mutation 0.95, animal model 0.60). IntOGen calls it a driver in 6 cohorts (6 activating, 0 loss-of-function), covering Bladder Urothelial Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:3434","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3434"},{"label":"UniProt P18074","url":"https://www.uniprot.org/uniprotkb/P18074/entry"},{"label":"NCBI Gene 2068","url":"https://www.ncbi.nlm.nih.gov/gene/2068"},{"label":"Ensembl ENSG00000104884","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104884"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["urothelial","skin-cancer","colorectal","ovarian","gastric","melanoma","nsclc","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: CIViC lists 5 therapies; IntOGen calls it an activating (Act) driver in 6 cohorts; CIViC holds 23 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"ERCC2","role":["drug-target","oncogene-driver","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:3434","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3434","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P18074","url":"https://www.uniprot.org/uniprotkb/P18074/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ERCC2","url":"https://civicdb.org/features/1736","note":"23 evidence items, 0 assertions, 15 variants; diseases: Bladder Carcinoma, Lung Non-small Cell Carcinoma, Bladder Urothelial Carcinoma, Melanoma, Osteosarcoma and 1 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000104884","url":"https://platform.opentargets.org/target/ENSG00000104884/associations","note":"association with cancer (MONDO_0004992) 0.83; per-cancer scores at or above 0.5: colorectal cancer 0.56, gastric cancer 0.50, urinary bladder cancer 0.73, ovarian cancer 0.51, melanoma 0.58, skin cancer 0.57 (GraphQL API, CC0)"},{"label":"IntOGen ERCC2","url":"https://www.intogen.org/search?gene=ERCC2","note":"driver in 6 cohorts (Act 6, 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 ERCC2: RNA low tissue specificity; high antibody staining in 3 normal tissues; highest cancer staining melanoma (3 of 12 high). Distribution: 7 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Bladder & urothelial cancer, Skin cancer (all types), Colorectal cancer, Ovarian cancer, Gastric & gastro-oesophageal junction cancer, Lung cancer (all types), Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 3 specific cancer types at or above 0.5 (xeroderma pigmentosum group D, urinary bladder cancer, urinary bladder carcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P18074","url":"https://www.uniprot.org/uniprotkb/P18074/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ERCC2","url":"https://civicdb.org/features/1736","note":"23 evidence items, 0 assertions, 15 variants; diseases: Bladder Carcinoma, Lung Non-small Cell Carcinoma, Bladder Urothelial Carcinoma, Melanoma, Osteosarcoma and 1 more (GraphQL API, CC0)"},{"label":"IntOGen ERCC2","url":"https://www.intogen.org/search?gene=ERCC2","note":"driver in 6 cohorts (Act 6, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas ERCC2 tissue","url":"https://www.proteinatlas.org/ENSG00000104884-ERCC2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000104884 associations","url":"https://platform.opentargets.org/target/ENSG00000104884/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:3434","ensembl":"ENSG00000104884","uniprot":"P18074","entrez":"2068","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Weber C.A. et al, EMBO J, 1990, \"ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2184031/","biology":"ATP-dependent 5'-3' DNA helicase. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, not absolutely essential for minimal transcription in vitro. Required for transcription-coupled nucleotide excision repair (NER) of damaged DNA; recognises damaged bases. Sequestered in chromatin on UV-damaged DNA. When complexed to CDK-activating kinase (CAK), involved in transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. Location: Nucleus; Cytoplasm, cytoskeleton, spindle (UniProt). Locus 19q13.32 (HGNC).","whereFound":["Bladder & urothelial cancer: Open Targets association 0.73 with urinary bladder cancer (MONDO_0001187); CIViC evidence names this disease","Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)","Colorectal cancer: Open Targets association 0.56 with colorectal cancer (MONDO_0005575)","Ovarian cancer: Open Targets association 0.51 with ovarian cancer (MONDO_0008170)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.50 with gastric cancer (MONDO_0001056)","Melanoma: Open Targets association 0.58 with melanoma (MONDO_0005105); CIViC evidence names this disease"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/ercc2/","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":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}