PALB2
PALB2 (Partner and localizer of BRCA2) 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 Breast cancer, Ovarian cancer, Colorectal cancer and 5 more.
Overview
Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. Strongly stimulates the DNA strand-invasion activity of RAD51, stabilises the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51.
CIViC holds 12 clinical evidence items and 0 assertions across 7 variants, naming Olaparib, Rucaparib, Talazoparib and Mitomycin. Open Targets scores its association with cancer at 0.91 (direct and indirect evidence; datatypes genetic literature 0.92, affected pathway 0.89, literature 0.99, genetic association 0.96, somatic mutation 0.90). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Ovarian Epithelial Tumour.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PALB2 (Partner and localizer of BRCA2) 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 Breast cancer, Ovarian cancer, Colorectal cancer and 5 more.
- 1 · What it is
PALB2 (Partner and localizer of BRCA2) 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 Breast cancer, Ovarian cancer, Colorectal cancer and 5 more.
- 2 · What goes wrong in cancer
Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
- 3 · How drugs use it
No product in this corpus aims at PALB2 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:26144 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q86YC2 (protein name, function text, keywords and locations (REST API)); CIViC gene PALB2 (12 evidence items, 0 assertions, 7 variants; diseases: Breast Cancer, Prostate Cancer, Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, Pancreatic Adenocarcinoma and 2 more (GraphQL API, CC0)); Open Targets ENSG00000083093 (association with cancer (MONDO_0004992) 0.91; per-cancer scores at or above 0.5: colorectal cancer 0.66, gastric cancer 0.63, prostate cancer 0.63, ovarian cancer 0.77, neuroendocrine neoplasm 0.50, acute myeloid leukaemia 0.53 (GraphQL API, CC0)); IntOGen PALB2 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. Strongly stimulates the DNA strand-invasion activity of RAD51, stabilises the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51. Serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is essential for homologous recombination. Via its WD repeats is proposed to scaffold a HR complex containing RAD51C and BRCA2 which is thought to play a role in HR-mediated DNA repair. Essential partner of BRCA2 that promotes the localisation and stability of BRCA2. Location: Nucleus (UniProt). Locus 16p12.2 (HGNC).
- Breast cancer: Open Targets association 0.87 with breast cancer (MONDO_0007254); CIViC evidence names this disease
- Ovarian cancer: Open Targets association 0.77 with ovarian cancer (MONDO_0008170); IntOGen driver in 1 cohort (OVT)
- Colorectal cancer: Open Targets association 0.66 with colorectal cancer (MONDO_0005575)
- Biliary tract cancer: Open Targets association 0.64 with biliary tract cancer (MONDO_0003060)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.63 with gastric cancer (MONDO_0001056)
- Prostate cancer: Open Targets association 0.63 with prostate cancer (MONDO_0008315); 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 4 therapies; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 12 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:"PALB2" OR ABSTRACT:"PALB2" OR TITLE:"partner and localizer of BRCA2" OR ABSTRACT:"partner and localizer of BRCA2" OR TITLE:"Partner and localizer of BRCA2" OR ABSTRACT:"Partner and localizer of BRCA2" OR TITLE:"FLJ21816" OR ABSTRACT:"FLJ21816" OR TITLE:"FANCN" OR ABSTRACT:"FANCN") 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 PALB2, not a curated reading list.
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