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    GENE:

    GEN1 (GEN1 Holliday junction 5' flap endonuclease)

    i
    Other names: GEN1, GEN1 Holliday Junction 5' Flap Endonuclease, Flap Endonuclease GEN Homolog 1, Holliday Junction Resolvase, Gen Endonuclease Homolog 1 (Drosophila), Gen Endonuclease Homolog 1, Gen
    Associations

    News

    Trials
    24d
    Exploration and Preliminary Investigation of Wiled Tinospora crispa: A Medicinal Plant with Promising Anti-Inflammatory and Antioxidant Properties. (PubMed, Curr Issues Mol Biol)
    Metabolomic characterization using UHPLC-ESI-QTOF-MS, supported by NMR, to confirm key compounds such as berberine, palmatine, chlorogenic acid, rutin, and borapetoside C. In vitro bioassays including: Antioxidant activity (e.g., radical-scavenging assay with EC50 determination)...Cultivation strategies that deliberately maintain or mimic beneficial stress conditions to preserve phytochemical richness. Broader geographical and genetic sampling to assess how generalizable the present chemotypic and bioactivity patterns are across the species.
    Journal
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    GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    chlorogenic acid
    1m
    Nivolumab + Docetaxel + ADT in mHSPC Patients With DDRD or Inflamed Tumors (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Xiao X. Wei, MD | Trial completion date: Dec 2025 --> Jun 2026
    Trial completion date
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    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    PD-L1 expression • MSI-H/dMMR
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    OncoPanel™ Assay
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    Opdivo (nivolumab) • docetaxel • goserelin acetate • Firmagon (degarelix) • leuprolide acetate for depot suspension
    6ms
    A novel DNA repair-independent role for Gen nuclease in promoting unscheduled polyploidy cell proliferation. (PubMed, PLoS Genet)
    Instead, Gen seems to influence polyploid DNA replication rates. This work identifies a novel function for Gen nuclease and provides new insights into the cellular and molecular requirements of non-physiological polyploidy.
    Journal
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    GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    6ms
    Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects (clinicaltrials.gov)
    P2, N=11, Active, not recruiting, Marc Dall'Era, MD | Recruiting --> Active, not recruiting | N=30 --> 11 | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jun 2025 --> Dec 2025
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    Zejula (niraparib)
    6ms
    GEN1 regulates cell proliferation, migration, apoptosis and ferroptosis in gastric cancer. (PubMed, World J Gastrointest Oncol)
    GEN1 promotes GC cell proliferation and migration while suppressing apoptosis and ferroptosis. Targeting GEN1 not only disrupts mitochondrial function and cell cycle progression but also sensitizes GC cells to ferroptosis and chemotherapy. These findings highlight GEN1 as a potential therapeutic target for enhancing treatment efficacy in gastric cancer.
    Journal
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    PLK1 (Polo Like Kinase 1) • GPX4 (Glutathione Peroxidase 4) • CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2) • ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4) • CCNB2 (Cyclin B2) • CCNB1 (Cyclin B1) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    cisplatin
    6ms
    Nivolumab + Docetaxel + ADT in mHSPC Patients With DDRD or Inflamed Tumors (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Xiao X. Wei, MD | Trial primary completion date: Oct 2024 --> Jul 2025
    Trial primary completion date
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    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    PD-L1 expression • MSI-H/dMMR
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    OncoPanel™ Assay
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    Opdivo (nivolumab) • docetaxel • goserelin acetate • Firmagon (degarelix) • leuprolide acetate for depot suspension
    6ms
    Durvalumab and Olaparib for the Treatment of Prostate Cancer in Men Predicted to Have a High Neoantigen Load (clinicaltrials.gov)
    P2, N=6, Terminated, University of Washington | Active, not recruiting --> Terminated; Slow accrual
    Trial termination
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    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    MSI-H/dMMR • HRD
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    Lynparza (olaparib) • Imfinzi (durvalumab)
    8ms
    Analysis of GEN1 as a Breast Cancer Susceptibility Gene in Polish Women. (PubMed, Int J Mol Sci)
    We conclude that GEN1 is unlikely to be a high or moderate-risk breast cancer susceptibility gene. Our study has clinical implications for genetic counseling and suggests that GEN1 changes should be reclassified as variants of uncertain significance (VUS) when they are detected in clinical testing panels.
    Journal
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    GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    8ms
    Nivolumab + Docetaxel + ADT in mHSPC Patients With DDRD or Inflamed Tumors (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Xiao X. Wei, MD | Trial completion date: Jun 2025 --> Dec 2025
    Trial completion date
    |
    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    PD-L1 expression • MSI-H/dMMR
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    OncoPanel™ Assay
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    Opdivo (nivolumab) • docetaxel • goserelin acetate • Firmagon (degarelix) • leuprolide acetate for depot suspension
    8ms
    EMVision CP2/Gen 1 Brain Scanner Device Study on Acute Stroke Participants. (ACTRN12623000070639)
    P=N/A, N=350, Completed, EMVision Medical Devices Ltd | Recruiting --> Completed
    Trial completion
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    GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    1year
    Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation. (PubMed, Am J Surg Pathol)
    Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.
    Journal
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    PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • PALB2 (Partner and localizer of BRCA2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • EWSR1 (EWS RNA Binding Protein 1) • KDM6A (Lysine Demethylase 6A) • EP300 (E1A binding protein p300) • DDX41 (DEAD-Box Helicase 41) • PHF6 (PHD Finger Protein 6) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • NFIB (Nuclear Factor I B) • RIT1 (Ras Like Without CAAX 1) • CHD2 (Chromodomain Helicase DNA Binding Protein 2) • DNM3 (Dynamin 3) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • MYBL1 (MYB Proto-Oncogene Like 1) • TAF1 (TATA-Box Binding Protein Associated Factor 1)
    1year
    OPTIMUM: Olaparib with or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy (clinicaltrials.gov)
    P2, N=62, Recruiting, Asan Medical Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • POLE (DNA Polymerase Epsilon) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    ATM mutation • CHEK2 mutation • BRIP1 mutation • BARD1 mutation
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    Lynparza (olaparib) • Imfinzi (durvalumab)