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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.
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.
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.
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.
Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
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).
Germline variant: UniProt lists Breast cancer (BC) under involvement in disease, and the record is a tumour suppressor; the medicines linked to it act through the loss (synthetic lethality) or use the variant to pick patients. HPA PALB2: RNA low tissue specificity; high antibody staining in 39 normal tissues; highest cancer staining lung cancer (12 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Biliary tract cancer (all types), Breast cancer (all types), Ovarian cancer, Colorectal cancer, Gastric & gastro-oesophageal junction cancer, Prostate cancer, Lung cancer (all types) and more); Open Targets associates it with 12 specific cancer types at or above 0.5 (breast cancer, breast carcinoma, hereditary breast ovarian cancer syndrome, familial pancreatic carcinoma, hereditary breast carcinoma, susceptibility to breast cancer and more). (Rule 2 of scripts/fetch-target-specificity.ts.)
Sources: UniProt Q86YC2; Human Protein Atlas PALB2 tissue; Open Targets ENSG00000083093 associations
First described 2004. Earliest sequence paper UniProt cites for the protein: Martin et al, Nature, 2004, "The sequence and analysis of duplication-rich human chromosome 16". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Bone marrow, Cerebellum, Lymph node.
Medium only: lymphoma.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Gallbladder cancer | 1.6% | Mutation | Mutation in 4 of 244 samples, 1.6%, in cBioPortal gbc_mskcc_2022. | cBioPortal (TCGA) |
| Triple-negative breast cancer | 1-2% | Germline or biallelic loss | 1.2% of 1,824 unselected patients (Couch 2015); 5 pathogenic germline variants among 237 whole genomes, 2.1%, two of them biallelic (Staaf 2019); 1.0% of 1,136 Nigerian breast cancer patients, eleven cases against no controls (Zheng 2018); cBioPortal: 2 of 176, 1.1%, in breast_msk_2018 and 1 of 123 in brca_tcga_pan_can_atlas_2018. | doi.org |
| Prostate cancer | 0.2-2% | PALB2, CHEK2, RAD51B/C/D, BARD1, BRIP1, FANCA, NBN inactivation | cBioPortal mutation in prostate_msk_2024 (2,260 samples): PALB2 19 (0.8%), CHEK2 14 (0.6%), BRIP1 17 (0.8%), BARD1 10 (0.4%), FANCA 15 (0.7%), RAD51B 6, RAD51C 3, RAD51D 2. Deep deletion adds a little: FANCA 42 of 2,260 (1.9%), CHEK2 5, PALB2 4, RAD51B 5. Germline in 692 men with metastatic disease: CHEK2 10 of 534 men with data, 1.9%; RAD51D 3, 0.4%; PALB2 3, 0.4% (Pritchard 2016). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 0.2-0.6% | Germline or somatic pathogenic variant | 2 of 854 germline, 0.2% (Shindo 2017); listed among the double-strand repair genes in 21 of 289 resected patients (Yurgelun 2019) and the 122 germline carriers of 615 (Lowery 2018); 15 of 2,336 tumours, 0.6%, in pdac_msk_2024 and 4 of 395 in pancreas_msk_2024 (cBioPortal). Six germline PALB2 carriers among 42 evaluable patients responded to maintenance rucaparib at 50%, 3 of 6 (Reiss 2021). Genomic instability co-segregated with BRCA1, BRCA2 or PALB2 inactivation in 100 whole genomes (Waddell 2015). | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
An argument for universal rather than criteria-based germline testing at diagnosis, with turnaround fast enough to inform surgery; for TNBC patients, who are already eligible, the lesson is timing.
It is the evidence that PALB2 and somatic BRCA2 belong in the PARP inhibitor conversation even though the olaparib label stops at germline BRCA.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
The rulebook behind the CAPS cohorts and the UK EUROPAC programme; it is also the reason surveillance for carriers is not yet a routine NHS service, because the consortium itself asked for it to stay within research until benefit was shown.
A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.
It is the best population-based estimate of how much TNBC is homologous recombination deficient, shows that most of it is not germline BRCA, and argues that whole-genome sequencing at diagnosis could stratify trials and pick out the low group that needs something other than DNA-damaging chemotherapy.
West Africa carries the highest germline burden reported for an unselected breast cancer population, and the genes are the same ones that predispose to TNBC elsewhere, so limited genetic services there should start with these families.
The broad-panel figure: one patient in five carries something inheritable, and about one in fifteen carries something treatable.
Query 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.
Shares Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer, Homologous recombination repair gene mutation in prostate cancer, CIViC.
Shares Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer, Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study, Homologous recombination repair gene mutation in prostate cancer.
Shares Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer, Inherited DNA-repair gene mutations in men with metastatic prostate cancer, Homologous recombination repair gene mutation in prostate cancer.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, 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, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma.
Shares Inherited DNA-repair gene mutations in men with metastatic prostate cancer, Homologous recombination repair gene mutation in prostate cancer, CIViC, IntOGen.
Shares Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma, Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection, Whole genomes redefine the mutational landscape of pancreatic cancer.
Shares Biliary tract cancer (all types), CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.