RAD50
RAD50 (DNA repair protein RAD50) 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 Ovarian cancer, Breast cancer, Colorectal cancer and 2 more.
Overview
Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases. The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage.
CIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Irinotecan and Checkpoint Kinase Inhibitor AZD7762. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes genetic literature 0.01, affected pathway 0.84, literature 0.94, genetic association 0.89, somatic mutation 0.78, animal model 0.62). IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Glioblastoma Multiforme.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · RAD50 (DNA repair protein RAD50) 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 Ovarian cancer, Breast cancer, Colorectal cancer and 2 more.
- 1 · What it is
RAD50 (DNA repair protein RAD50) 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 Ovarian cancer, Breast cancer, Colorectal cancer and 2 more.
- 2 · What goes wrong in cancer
Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
- 3 · How drugs use it
No product in this corpus aims at RAD50 yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:9816 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q92878 (protein name, function text, keywords and locations (REST API)); CIViC gene RAD50 (1 evidence items, 0 assertions, 1 variants; diseases: Ureter Small Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000113522 (association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: colorectal cancer 0.55, prostate cancer 0.51, ovarian cancer 0.67, breast cancer 0.66 (GraphQL API, CC0)); IntOGen RAD50 (driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases. The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage. The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination. Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11. RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form. Location: Nucleus; Chromosome, telomere; Chromosome (UniProt). Locus 5q31.1 (HGNC).
- Ovarian cancer: Open Targets association 0.67 with ovarian cancer (MONDO_0008170)
- Breast cancer: Open Targets association 0.66 with breast cancer (MONDO_0007254)
- Colorectal cancer: Open Targets association 0.55 with colorectal cancer (MONDO_0005575)
- Prostate cancer: Open Targets association 0.51 with prostate cancer (MONDO_0008315)
- Glioma & glioblastoma: IntOGen driver in 1 cohort (GBM)
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 2 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; CIViC holds 1 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: Ureter Small Cell Carcinoma.
Latest papers
topQuery for this target: (TITLE:"RAD50" OR ABSTRACT:"RAD50" OR TITLE:"RAD50 double strand break repair protein" OR ABSTRACT:"RAD50 double strand break repair protein" OR TITLE:"DNA repair protein RAD50" OR ABSTRACT:"DNA repair protein RAD50" OR TITLE:"hRad50" OR ABSTRACT:"hRad50" OR TITLE:"RAD50-2" OR ABSTRACT:"RAD50-2") 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 RAD50, not a curated reading list.