{"entity":{"id":"palb2","kind":"target","name":"PALB2","aka":["partner and localizer of BRCA2","Partner and localizer of BRCA2","FLJ21816","FANCN"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:26144","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:26144"},{"label":"UniProt Q86YC2","url":"https://www.uniprot.org/uniprotkb/Q86YC2/entry"},{"label":"NCBI Gene 79728","url":"https://www.ncbi.nlm.nih.gov/gene/79728"},{"label":"Ensembl ENSG00000083093","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000083093"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","ovarian","colorectal","biliary-tract-cancer","gastric","prostate","lung-cancer","pancreatic","tnbc","gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-couch-tnbc-germline-17-genes-jco-2015","paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019","paper-zheng-nigerian-inherited-breast-cancer-jco-2018","paper-shindo-germline-sporadic-pancreatic-jco-2017","paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019","paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021","paper-waddell-whole-genomes-pancreatic-nature-2015","paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016"],"journals":[],"dependsOn":[],"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PALB2","role":["drug-target","tumour-suppressor","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:26144","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:26144","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q86YC2","url":"https://www.uniprot.org/uniprotkb/Q86YC2/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PALB2","url":"https://civicdb.org/features/15013","note":"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)"},{"label":"Open Targets ENSG00000083093","url":"https://platform.opentargets.org/target/ENSG00000083093/associations","note":"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)"},{"label":"IntOGen PALB2","url":"https://www.intogen.org/search?gene=PALB2","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"germline-variant","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt Q86YC2","url":"https://www.uniprot.org/uniprotkb/Q86YC2/entry","note":"involvement in disease"},{"label":"Human Protein Atlas PALB2 tissue","url":"https://www.proteinatlas.org/ENSG00000083093-PALB2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000083093 associations","url":"https://platform.opentargets.org/target/ENSG00000083093/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:26144","ensembl":"ENSG00000083093","uniprot":"Q86YC2","entrez":"79728","firstDescribed":2004,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Martin et al, Nature, 2004, \"The sequence and analysis of duplication-rich human chromosome 16\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/15616553/","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).","whereFound":["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"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"tnbc","pct":"1-2","measure":"Germline or biallelic loss","source":"https://doi.org/10.1200/JCO.2014.57.1414","note":"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."},{"cancerId":"pancreatic","pct":"0.2-0.6","measure":"Germline or somatic pathogenic variant","source":"https://doi.org/10.1200/JCO.2017.72.3502","note":"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)."},{"cancerId":"gallbladder","pct":"1.6","measure":"Mutation","source":"https://www.cbioportal.org/study/summary?id=gbc_mskcc_2022","note":"Mutation in 4 of 244 samples, 1.6%, in cBioPortal gbc_mskcc_2022."},{"cancerId":"prostate","pct":"0.2-2","measure":"PALB2, CHEK2, RAD51B/C/D, BARD1, BRIP1, FANCA, NBN inactivation","source":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024","note":"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)."}]},"route":"/targets/palb2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"paper":[{"id":"paper-connor-mutational-signatures-immune-pancreatic-jama-oncol-2017","kind":"paper","name":"Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma","route":"/key-papers/paper-connor-mutational-signatures-immune-pancreatic-jama-oncol-2017/"},{"id":"paper-shindo-germline-sporadic-pancreatic-jco-2017","kind":"paper","name":"Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma","route":"/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/"},{"id":"paper-park-hrd-pancreatic-platinum-ccr-2020","kind":"paper","name":"Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection","route":"/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/"},{"id":"paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019","kind":"paper","name":"Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer","route":"/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/"},{"id":"paper-zheng-nigerian-inherited-breast-cancer-jco-2018","kind":"paper","name":"Inherited breast cancer in Nigerian women","route":"/key-papers/paper-zheng-nigerian-inherited-breast-cancer-jco-2018/"},{"id":"paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","kind":"paper","name":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","route":"/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/"},{"id":"paper-couch-tnbc-germline-17-genes-jco-2015","kind":"paper","name":"Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer","route":"/key-papers/paper-couch-tnbc-germline-17-genes-jco-2015/"},{"id":"paper-caps-consortium-surveillance-recommendations-gut-2020","kind":"paper","name":"Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","route":"/key-papers/paper-caps-consortium-surveillance-recommendations-gut-2020/"},{"id":"paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021","kind":"paper","name":"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","route":"/key-papers/paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021/"},{"id":"paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","kind":"paper","name":"Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms","route":"/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/"},{"id":"paper-hudson-phillips-expanded-germline-testing-clin-breast-cancer-2026","kind":"paper","name":"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","route":"/key-papers/paper-hudson-phillips-expanded-germline-testing-clin-breast-cancer-2026/"},{"id":"paper-shimelis-tnbc-risk-genes-jnci-2018","kind":"paper","name":"Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing","route":"/key-papers/paper-shimelis-tnbc-risk-genes-jnci-2018/"},{"id":"paper-waddell-whole-genomes-pancreatic-nature-2015","kind":"paper","name":"Whole genomes redefine the mutational landscape of pancreatic cancer","route":"/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/"},{"id":"paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019","kind":"paper","name":"Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study","route":"/key-papers/paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019/"}],"term":[{"id":"familial-pancreatic-cancer","kind":"term","name":"Familial pancreatic cancer and inherited risk (who qualifies for surveillance)","route":"/terms/familial-pancreatic-cancer/"}],"trial":[{"id":"europac","kind":"trial","name":"EUROPAC","route":"/trials/europac/"}],"biomarker":[{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"}]}}