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    GENE:

    ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit)

    i
    Other names: ERCC4, ERCC Excision Repair 4, Endonuclease Catalytic Subunit, FANCQ, RAD1, XPF, Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 4, Xeroderma Pigmentosum Group F-Complementing Protein, Xeroderma Pigmentosum, Complementation Group F, Excision Repair Cross-Complementation Group 4, DNA Repair Protein Complementing XP-F Cells, DNA Excision Repair Protein ERCC-4, DNA Repair Endonuclease XPF, ERCC11, Excision-Repair, Complementing Defective, In Chinese Hamster, XFEPS
    1m
    The association between DNA repair genes polymorphisms and cisplatin-induced ototoxicity in cancer patients: a systematic review. (PubMed, Per Med)
    Although several DNA repair gene polymorphisms have been explored, findings remain inconsistent and limited by populations and SNPs studied. Larger, well-designed studies with standardized methodologies are needed to confirm these associations and identify genetic markers for predicting high-risk patients for CIO.
    Review • Journal
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    ERCC1 (Excision repair cross-complementation group 1) • ERCC2 (Excision repair cross-complementation group 2) • GSTP1 (Glutathione S-transferase pi 1) • FASLG (Fas ligand) • MSH3 (MutS Homolog 3) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2) • XPC (XPC Complex Subunit, DNA Damage Recognition And Repair Factor) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • XPA (XPA, DNA Damage Recognition And Repair Factor) • XRCC1 (X-Ray Repair Cross Complementing 1)
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    cisplatin
    2ms
    Ginsenoside Rh2 Suppresses the Fanconi Anemia Pathway by Inhibiting NF-κB-Mediated FANCL Transcription in Bladder Cancer. (PubMed, Dose Response)
    Ginsenoside Rh2 suppresses NF-κB signaling to transcriptionally downregulate FANCL, thereby impairing FA pathway-mediated DNA repair and enhancing cisplatin cytotoxicity in bladder cancer. These findings highlight Rh2 as a potential combinatorial agent to overcome platinum resistance.
    Journal
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    FANCL (FA Complementation Group L) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    cisplatin
    3ms
    Piperine Targets the FANCL/UBE2T Complex to Inhibit the FA Pathway and Sensitize Bladder Cancer to Cisplatin. (PubMed, Dose Response)
    Our findings uncover piperine as a natural compound that allosterically inhibits UBE2T activity within the FA pathway, thereby impairing ID2 monoubiquitination and enhancing cisplatin sensitivity in bladder cancer. This study highlights the therapeutic potential of piperine and provides a rationale for targeting the FA repair axis to overcome platinum resistance.
    Journal
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    FANCL (FA Complementation Group L) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit) • USP1 (Ubiquitin Specific Peptidase 1)
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    cisplatin
    3ms
    The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer. (PubMed, bioRxiv)
    We propose a model in which ssDNA gaps, when extended beyond a critical length, become inaccessible to TLS-mediated repair and are fully reliant on homologous recombination. These findings establish the 9-1-1 complex as key regulator of ssDNA gap stability and a promising therapeutic target in BRCA2-deficient cancers.
    Journal
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    BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • RAD9A (RAD9 Checkpoint Clamp Component A)
    4ms
    Lactylation Enhances the Activity of Lactate Dehydrogenase A and Promotes the Chemoresistance to Cisplatin Through Facilitating DNA Nonhomologous End Junction in Lung Adenocarcinoma. (PubMed, Adv Sci (Weinh))
    Delactylation of these proteins significantly hinders the formation of FEN1-RAD1-RAD9A-HUS1 complex, thereby leading to dysfunction of NHEJ and increasing the sensitivity of cancer cells to cisplatin. In summary, this work identifies LDHA lactylation as a critical mechanism for accelerating the progression of LUAD and reveals how this lactylation influenced cisplatin sensitivity of LUAD cells, which deepen the understanding of lactylation-mediated tumor progression and provide a potential new anticancer strategy.
    Journal
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    LDHA (Lactate dehydrogenase A) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FEN1 (Flap Structure-Specific Endonuclease 1) • RAD9A (RAD9 Checkpoint Clamp Component A)
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    cisplatin
    5ms
    PRMT5 genetic interactions with DNA double strand break repair genes. (PubMed, PLoS One)
    For example, inhibition of the 9-1-1 complex in a PRMT5 mutant may selectively kill the cell. Given that PRMT5 small molecule inhibitors are being developed or already deployed, these findings should inform potential applications of these drugs.
    Journal
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    PRMT5 (Protein Arginine Methyltransferase 5) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit)
    5ms
    Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry. (PubMed, Nat Commun)
    Besides notable impact of DNA polymerases, including POLG, Fanconi anaemia genes include FANCD2, FANCA, FANCG, ERCC4, FANCE and FANCI, while DNA mismatch repair genes MSH3 and PMS1 outranked known namesakes MSH6 and PMS2. This study provides insights into the spectrum of African-relevant potentially pathogenic PCa variants, highlighting much-needed gene candidates for ancestry-inclusive germline testing.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • LRP1B (LDL Receptor Related Protein 1B) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • FAT1 (FAT atypical cadherin 1) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MSH3 (MutS Homolog 3) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • PMS1 (PMS1 protein homolog 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • HOXB13 (Homeobox B13)
    5ms
    SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
    P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2027 --> Jun 2040 | Trial primary completion date: Dec 2026 --> Dec 2038
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
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    HER-2 mutation • AKT1 mutation
    6ms
    Cancer-associated fibroblast derived CXCL14 drives cisplatin chemoresistance by enhancing nucleotide excision repair in bladder cancer. (PubMed, J Exp Clin Cancer Res)
    The CXCL14/CCR7/STAT3 axis critically mediates cisplatin resistance in bladder cancer through dual modulation of DNA repair and glycolytic metabolism. Therapeutic cotargeting of this pathway with CCR7 or STAT3 inhibitors combined with cisplatin represents a promising strategy to overcome chemoresistance and improve clinical outcomes.
    Journal
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    LDHA (Lactate dehydrogenase A) • CCR7 (Chemokine (C-C motif) receptor 7) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • CXCL14 (C-X-C Motif Chemokine Ligand 14)
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    cisplatin
    6ms
    Potential role of Fanconi anemia pathway in the pathogenesis of endometrial cancer (Review). (PubMed, Mol Med Rep)
    This comprehensive review provides a systematic summary of EC‑related FA genes, elucidates the roles of various FA genes in EC and further speculates on their related mechanisms to facilitate the development of targeted therapies that specifically target key genes, leading to a more accurate and efficient treatment for EC. The present review searched PubMed and Google Scholar for articles published in English up to June 2025 using keywords such as Fanconi anemia pathway, 22 FA genes (FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, FANCO/RAD51C, FANCP/SLX4, FANCQ/XPF, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7, FANCW/RFWD3), endometrial cancer (type I: Endometrioid adenocarcinoma; Type II Uterine serous carcinoma, clear‑cell carcinoma, carcinosarcoma), somatic copy number alterations, microsatellite instability, TP53 mutations, pathogenesis, genomic instability, target therapy.
    Review • Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    TP53 mutation
    8ms
    High burden of variants of uncertain significance in early-onset colorectal cancer among indigenous African patients: a call for global research equity in cancer genetics. (PubMed, Mol Biol Rep)
    Our findings reveal a high burden of potentially pathogenic VUSs in indigenous African patients with eoCRC, reflecting both unique genetic architecture and a critical gap in global genomic equity. These variants may contribute to future variant reclassification and improved understanding of CRC predisposition in African populations. This study underscores the urgent need for population-specific genomic research and the development of inclusive variant databases to support accurate diagnosis and personalised care.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • ASXL1 (ASXL Transcriptional Regulator 1) • WT1 (WT1 Transcription Factor) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • FAT1 (FAT atypical cadherin 1) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • IR (Insulin receptor) • MITF (Melanocyte Inducing Transcription Factor) • PYCR1 (Pyrroline-5-Carboxylate Reductase 1) • RECQL (RecQ Like Helicase) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • RASA1 (RAS P21 Protein Activator 1) • UGT1A7 (UDP Glucuronosyltransferase Family 1 Member A7)