# PALB2

Source: https://onco.cc/targets/palb2/  
OnCo record `palb2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: partner and localizer of BRCA2; Partner and localizer of BRCA2; FLJ21816; FANCN
- Tags: cancer-genes-wave
- Symbol: PALB2
- Class: tumor-suppressor
- 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).
- Where found: 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; Triple-negative breast cancer: germline or biallelic loss 1-2%; Pancreatic ductal adenocarcinoma: germline or somatic pathogenic variant 0.2-0.6%; Gallbladder cancer: mutation 1.6%; Prostate cancer: palb2, chek2, rad51b/c/d, bard1, brip1, fanca, nbn inactivation 0.2-2% depending on disease state

## 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 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.
- Triple-negative breast cancer: a high-risk TNBC gene (odds ratio above 5; Shimelis 2018) carried by 1.2% of unselected patients (Couch 2015) and 1.0% of Nigerian breast cancer patients (Zheng 2018); biallelic PALB2 loss gives a BRCA2-null mutational phenotype (Staaf 2019). Olaparib's OlympiA label covers germline BRCA only.
- Pancreatic ductal adenocarcinoma: germline variants in about 0.2 to 0.6% (Shindo 2017; cBioPortal 15 of 2,336 tumours). Biallelic PALB2 loss produces the unstable genome and repair-deficiency signature that predicts platinum response (Waddell 2015), and 3 of 6 germline PALB2 carriers responded to maintenance rucaparib (Reiss 2021), although no PARP inhibitor label covers PALB2 in this disease.

## Sources

- HGNC HGNC:26144: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:26144
- UniProt Q86YC2: https://www.uniprot.org/uniprotkb/Q86YC2/entry
- NCBI Gene 79728: https://www.ncbi.nlm.nih.gov/gene/79728
- Ensembl ENSG00000083093: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000083093

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- key papers: [Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-connor-mutational-signatures-immune-pancreatic-jama-oncol-2017/), [Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/), [Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection](https://onco.cc/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/), [Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer](https://onco.cc/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/), [Inherited breast cancer in Nigerian women](https://onco.cc/key-papers/paper-zheng-nigerian-inherited-breast-cancer-jco-2018/), [Inherited DNA-repair gene mutations in men with metastatic prostate cancer](https://onco.cc/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/), [Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer](https://onco.cc/key-papers/paper-couch-tnbc-germline-17-genes-jco-2015/), [Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium](https://onco.cc/key-papers/paper-caps-consortium-surveillance-recommendations-gut-2020/), [Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2](https://onco.cc/key-papers/paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021/), [Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms](https://onco.cc/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/), [The impact of expanded access to germline high penetrance genetic testing for women with a new diagnosis of invasive breast cancer or high-grade DCIS](https://onco.cc/key-papers/paper-hudson-phillips-expanded-germline-testing-clin-breast-cancer-2026/), [Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing](https://onco.cc/key-papers/paper-shimelis-tnbc-risk-genes-jnci-2018/), [Whole genomes redefine the mutational landscape of pancreatic cancer](https://onco.cc/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/), [Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study](https://onco.cc/key-papers/paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019/)
- terms: [Familial pancreatic cancer and inherited risk (who qualifies for surveillance)](https://onco.cc/terms/familial-pancreatic-cancer/)
- trials: [EUROPAC](https://onco.cc/trials/europac/)
- biomarkers: [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/)

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JSON: https://onco.cc/api/v1/entities/palb2.json