PALB2

Chr 16ADAR

partner and localizer of BRCA2

Also known as: BROVCA5, FANCN, PNCA3

NCBI Gene: 79728ENSG00000083093UniProt: Q86YC2OMIM: 610355

The PALB2 protein plays a critical role in homologous recombination DNA repair by recruiting BRCA2 and RAD51 to DNA breaks and serving as a molecular scaffold for the BRCA1-PALB2-BRCA2 complex. Biallelic mutations cause Fanconi anemia complementation group N with bone marrow failure and cancer predisposition, following autosomal recessive inheritance, while monoallelic mutations increase susceptibility to breast, ovarian, and pancreatic cancers with autosomal dominant inheritance. The gene is extremely intolerant to loss-of-function variants (pLI near 0), reflecting its essential cellular function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 1.013 OMIM phenotypes
Clinical Summary— PALB2
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Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group N · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
91 unique Pathogenic / Likely Pathogenic· 168 VUS of 400 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — PALB2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.52
OE 0.76 (0.58–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.28Z-score
OE missense 0.97 (0.90–1.04)
568 obs / 586.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.58–1.01)
0≤0.351.4
Missense OE0.97 (0.90–1.04)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 35 / 46.1Missense obs/exp: 568 / 586.8Syn Z: -0.73

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic22
VUS168
Likely Benign88
Benign39
Conflicting3
69
Pathogenic
22
Likely Pathogenic
168
VUS
88
Likely Benign
39
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
64
1
4
0
69
Likely Pathogenic
15
2
5
0
22
VUS
2
157
8
1
168
Likely Benign
0
20
35
33
88
Benign
0
0
6
33
39
Conflicting
—3
Total811805867389

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PALB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast CancerGenetic Susceptibility

ScreenIng of Genetic Susceptibility Genes for Breast Cancer Patients in CHinese communiTies

RECRUITING
NCT04265937Fudan UniversityStarted 2019-07-01
Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING
NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01
ST-01156
Breast Cancer

Assessing Clinical Features and Outcome of Breast Cancer in PALB2 Mutation Carriers: the Palbreast Study

RECRUITING
NCT06403904Azienda Ospedaliero-Universitaria di ModenaStarted 2023-10-02
Malignant Neoplasm of BreastBreast Cancer

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO

ACTIVE NOT RECRUITING
NCT05033756Phase PHASE2Institut fuer FrauengesundheitStarted 2022-07-30
Pembrolizumab Injection [Keytruda]Olaparib Oral Tablet [Lynparza]
Pancreatic CancerPancreatic Ductal AdenocarcinomaPDAC

A Prospective Registry for Patients at High-Risk for Pancreatic Cancer

RECRUITING
NCT06151223Mayo ClinicStarted 2021-07-13
Bio-specimen Collection: BloodBio-specimen Collection: Pancreatic JuiceMRI
Breast CancerPALB2-Mutated Breast CarcinomaHER2-negative Breast Cancer

Phase Ib Study of Axatilimab in Combination With Olaparib in BRCA1/2 and PALB2- Associated Metastatic HER2-negative Breast Cancer

RECRUITING
NCT06488378Phase PHASE1Dana-Farber Cancer InstituteStarted 2024-08-13
AxatilimabOlaparib
Metastatic Solid TumorBRCA1 MutationBRCA2 Mutation

Combination Therapy in Cancers With Mutations in DNA Repair Genes

RECRUITING
NCT05694715Phase PHASE1University of California, San FranciscoStarted 2023-05-23
NiraparibIrinotecan
Prostate Cancer

PROMISE Registry: A Prostate Cancer Registry of Outcomes and Germline Mutations for Improved Survival and Treatment Effectiveness

RECRUITING
NCT04995198Prostate Cancer Clinical Trials ConsortiumStarted 2021-05-03
Pancreatic Acinar Cell CarcinomaPancreatic AdenocarcinomaPancreatic Adenosquamous Carcinoma

The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer

ACTIVE NOT RECRUITING
NCT06115499Phase PHASE2, PHASE3Alliance for Clinical Trials in OncologyStarted 2024-08-13
Nab paclitaxelGemcitabineCisplatin
BRCA MutationPALB2 Gene MutationDuctal Carcinoma in Situ

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion

ACTIVE NOT RECRUITING
NCT06033092Phase PHASE2European Institute of OncologyStarted 2024-06-21
Tamoxifen 10 mg TabletIntermittent caloric restrictionStep counter Device
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Uveal Melanoma

Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma

RECRUITING
NCT06550674Phase NACentre Jean PerrinStarted 2024-10-29
Constitutional exome analysis
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2.
Huffman BM et al.·Clin Cancer Res
2026Cohort
Investigating the contribution of rare non-coding variants in BRCA1, BRCA2 and PALB2 to hereditary breast cancer.
Zhao Q et al.·NPJ Breast Cancer
2026
High Prevalence of Non-BRCA Pathogenic Variants and a Recurrent PALB2 Variant in an Argentine Hereditary Breast and Ovarian Cancer Cohort.
Martin CA et al.·Cancer Med
2026Open AccessCohort
Unique social, identity, and community factors impact prophylactic surgery discussions in young adults who are BRCA1, BRCA2, and PALB2 positive.
Boye A et al.·J Genet Couns
2026
Prediction of Specific Survival and Clinicopathological Impact of Somatic PALB2 Mutations and Pathogenic/Likely Pathogenic Variants (PV/LPV) in Breast Cancer: A Cohort Study of 81 Patients.
Hawsawi YM et al.·Int J Surg Pathol
2026Cohort
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients