ERCC3
ERCC3 (General transcription and DNA repair factor IIH helicase/translocase subunit XPB) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Cervical cancer, Skin cancer, Ovarian cancer and 3 more.
Overview
ATP-dependent 3'-5' DNA helicase/translocase. Binds dsDNA rather than ssDNA, unzipping it in a translocase rather than classical helicase activity. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex.
CIViC holds 3 clinical evidence items and 0 assertions across 1 variant, naming Immune Checkpoint Inhibitor. Open Targets scores its association with cancer at 0.69 (direct and indirect evidence; datatypes literature 0.91, genetic association 0.44, somatic mutation 0.85). IntOGen calls it a driver in 2 cohorts (0 activating, 2 loss-of-function), covering Cervical Squamous Cell Carcinoma, Melanoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · ERCC3 (General transcription and DNA repair factor IIH helicase/translocase subunit XPB) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Cervical cancer, Skin cancer, Ovarian cancer and 3 more.
- 1 · What it is
ERCC3 (General transcription and DNA repair factor IIH helicase/translocase subunit XPB) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Cervical cancer, Skin cancer, Ovarian cancer and 3 more.
- 2 · What goes wrong in cancer
ATP-dependent 3'-5' DNA helicase/translocase. Binds dsDNA rather than ssDNA, unzipping it in a translocase rather than classical helicase activity.
- 3 · How drugs use it
No product in this corpus aims at ERCC3 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:3435 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P19447 (protein name, function text, keywords and locations (REST API)); CIViC gene ERCC3 (3 evidence items, 0 assertions, 1 variants; diseases: Melanoma, Lung Non-small Cell Carcinoma, Cancer (GraphQL API, CC0)); Open Targets ENSG00000163161 (association with cancer (MONDO_0004992) 0.69; per-cancer scores at or above 0.5: colorectal cancer 0.52, ovarian cancer 0.53, melanoma 0.55, skin cancer 0.54 (GraphQL API, CC0)); IntOGen ERCC3 (driver in 2 cohorts (Act 0, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
ATP-dependent 3'-5' DNA helicase/translocase. Binds dsDNA rather than ssDNA, unzipping it in a translocase rather than classical helicase activity. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex. When complexed to CDK-activating kinase (CAK), involved in RNA transcription by RNA polymerase II. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening; it may wrap around the damaged DNA wedging it open, causing localised melting that allows XPD/ERCC2 helicase to anchor. In transcription, TFIIH has an essential role in transcription initiation. Location: Nucleus (UniProt). Locus 2q14.3 (HGNC).
- Cervical cancer: IntOGen driver in 1 cohort (CESC)
- Skin cancer: Open Targets association 0.54 with skin cancer (MONDO_0002898)
- Ovarian cancer: Open Targets association 0.53 with ovarian cancer (MONDO_0008170)
- Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575)
- Melanoma: Open Targets association 0.55 with melanoma (MONDO_0005105); CIViC evidence names this disease
- Non-small-cell lung cancer: CIViC evidence names this disease
Notes
top- 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 1 therapies; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 3 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.
Latest papers
topQuery for this target: (TITLE:"ERCC3" OR ABSTRACT:"ERCC3" OR TITLE:"ERCC excision repair 3, TFIIH core complex helicase subunit" OR ABSTRACT:"ERCC excision repair 3, TFIIH core complex helicase subunit" OR TITLE:"General transcription and DNA repair factor IIH helicase/translocase subunit XPB" OR ABSTRACT:"General transcription and DNA repair factor IIH helicase/translocase subunit XPB" OR TITLE:"BTF2" OR ABSTRACT:"BTF2" OR TITLE:"RAD25" OR ABSTRACT:"RAD25" OR TITLE:"Ssl2" OR ABSTRACT:"Ssl2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ERCC3, not a curated reading list.