{"gene":"ZNF280A","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":2025,"finding":"ZNF280A is recruited to DNA double-strand break (DSB) sites and is essential for DSB repair by homologous recombination. Mechanistically, ZNF280A promotes long-range DNA-end resection by facilitating the recruitment of the BLM-DNA2 helicase-nuclease complex to DSB sites and enhancing the enzymatic activity of this complex at DNA damage sites. Loss of ZNF280A drives genomic instability and sensitivity to DNA-damaging agents.","method":"High-throughput microscopy with cDNA 'chromORFeome' library screen, loss-of-function experiments, recruitment assays to DSB sites, BLM-DNA2 complex recruitment and enzymatic activity assays, rescue by ZNF280A reintroduction in patient-derived cells","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — mechanistic assays (enzymatic activity, complex recruitment), multiple orthogonal methods, genetic rescue in human patient-derived cells, single rigorous study","pmids":["40523937"],"is_preprint":false},{"year":2021,"finding":"ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C; downregulation of EIF3C in ZNF280A-overexpressed cells attenuated ZNF280A-induced tumor promotion, placing EIF3C as a downstream effector of ZNF280A.","method":"Gene expression profiling after ZNF280A knockdown, loss-of-function and overexpression in vitro and in vivo, epistasis rescue experiment (EIF3C knockdown in ZNF280A-overexpressed cells)","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — epistasis rescue experiment and expression profiling support pathway placement, single lab, multiple functional assays but no direct biochemical interaction demonstrated","pmids":["33414445"],"is_preprint":false},{"year":2019,"finding":"ZNF280A promotes colorectal cancer cell proliferation by inactivating the Hippo signaling pathway; silencing ZNF280A activated Hippo signaling and suppressed proliferation with G0/G1 arrest.","method":"Western blot and luciferase reporter assays for Hippo pathway activity, siRNA-mediated silencing, in vitro proliferation assays, in vivo xenograft","journal":"Molecular therapy oncolytics","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — pathway placement by Western blot and luciferase assay, single lab, single study","pmids":["30847384"],"is_preprint":false},{"year":2022,"finding":"ZNF280A knockdown promotes the ubiquitination and degradation of RPS14 in colorectal cancer cells, and RPS14 in turn regulates CRC development via the PI3K-Akt signaling pathway, establishing a ZNF280A/RPS14/PI3K-Akt axis.","method":"Loss-of-function (ZNF280A knockdown), ubiquitination assays, Western blot for RPS14 protein levels and PI3K-Akt pathway components, in vitro and in vivo functional assays","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — ubiquitination assay establishes downstream regulatory mechanism, single lab, single study","pmids":["36059657"],"is_preprint":false},{"year":2025,"finding":"ZNF280A enhances ACRV1 transcription by interacting with the transcription factor CUX2 and facilitating CUX2 recruitment to the ACRV1 promoter; elevated ZNF280A or ACRV1 activates PI3K/AKT signaling and increases glycolytic enzyme expression (PKM2, LDHA), glucose uptake, lactate production, and ATP generation in ovarian cancer cells.","method":"Co-immunoprecipitation/interaction assays between ZNF280A and CUX2, chromatin recruitment assay to ACRV1 promoter, knockdown/overexpression functional assays, metabolic assays (glucose uptake, lactate, ATP, ECAR), pharmacological AKT/glycolysis inhibition rescue","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — Co-IP interaction and promoter recruitment assay with pharmacological rescue, single lab, single study","pmids":["41338461"],"is_preprint":false},{"year":2025,"finding":"ZNF280A knockdown in malignant melanoma cells leads to increased apoptosis and cell cycle arrest associated with upregulation of p53 expression, suggesting ZNF280A regulates p53 levels in this context.","method":"shRNA-mediated knockdown, Western blot for p53, flow cytometry for apoptosis and cell cycle, in vitro and in vivo functional assays","journal":"Discover oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (Western blot for p53), limited mechanistic depth","pmids":["40251414"],"is_preprint":false}],"current_model":"ZNF280A is a chromatin-associated zinc finger protein that functions primarily as a promoter of long-range DNA-end resection during homologous recombination by facilitating recruitment of the BLM-DNA2 helicase-nuclease complex to double-strand break sites; in cancer contexts it also acts as a transcriptional regulator that drives tumor progression through downstream effectors including EIF3C, RPS14/PI3K-Akt, and CUX2-ACRV1-PI3K/AKT axes, and modulates the Hippo signaling pathway."},"narrative":{"mechanistic_narrative":"ZNF280A is a chromatin-associated zinc finger protein that operates at the interface of genome maintenance and oncogenic signaling [PMID:40523937, PMID:33414445]. Its best-defined molecular function is in DNA double-strand break repair: ZNF280A is recruited to break sites and promotes long-range DNA-end resection during homologous recombination by facilitating recruitment of the BLM-DNA2 helicase-nuclease complex and enhancing its enzymatic activity, such that loss of ZNF280A causes genomic instability and sensitivity to DNA-damaging agents [PMID:40523937]. In cancer settings ZNF280A behaves as a tumor-promoting factor that acts through multiple downstream effectors: it sustains EIF3C expression to drive lung adenocarcinoma [PMID:33414445], stabilizes RPS14 against ubiquitin-mediated degradation to engage PI3K-Akt signaling in colorectal cancer [PMID:36059657], and interacts with the transcription factor CUX2 to enhance ACRV1 transcription, activating PI3K/AKT signaling and glycolytic metabolism in ovarian cancer [PMID:41338461]. It additionally inactivates Hippo signaling to support proliferation [PMID:30847384]. Beyond these contexts, the structural basis of ZNF280A's DNA/chromatin association and its direct transcriptional targets have not been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Whether ZNF280A had any role in tumor cell proliferation was unknown; this work placed it as a driver of colorectal cancer growth acting through Hippo pathway inactivation.","evidence":"siRNA silencing with luciferase reporter and Western blot for Hippo activity, proliferation assays, and xenografts in colorectal cancer","pmids":["30847384"],"confidence":"Medium","gaps":["No direct molecular interaction linking ZNF280A to Hippo components","Mechanism of pathway regulation (transcriptional vs post-translational) undefined"]},{"year":2021,"claim":"To identify ZNF280A's pro-tumor effectors, this study established EIF3C as a downstream mediator required for ZNF280A-induced lung adenocarcinoma promotion.","evidence":"Expression profiling after knockdown plus epistasis rescue (EIF3C knockdown in ZNF280A-overexpressing cells) in vitro and in vivo","pmids":["33414445"],"confidence":"Medium","gaps":["No demonstration that ZNF280A binds the EIF3C locus directly","Whether regulation is transcriptional remains unresolved"]},{"year":2022,"claim":"Building on cancer roles, this work added a post-translational axis whereby ZNF280A protects RPS14 from ubiquitin-mediated degradation to engage PI3K-Akt signaling.","evidence":"Knockdown with ubiquitination assays and Western blot for RPS14 and PI3K-Akt components, functional assays in colorectal cancer cells","pmids":["36059657"],"confidence":"Medium","gaps":["Mechanism by which ZNF280A controls RPS14 ubiquitination is unknown","No identified E3 ligase or direct binding"]},{"year":2025,"claim":"The molecular function of ZNF280A had remained obscure; a chromORFeome screen revealed it is a DSB repair factor that promotes long-range resection via the BLM-DNA2 complex.","evidence":"High-throughput microscopy screen, recruitment assays to DSB sites, BLM-DNA2 complex recruitment and enzymatic activity assays, and rescue in patient-derived cells","pmids":["40523937"],"confidence":"High","gaps":["No structure of ZNF280A or its DNA/chromatin contacts","Direct physical interaction interface with BLM-DNA2 not mapped","Relationship between resection role and oncogenic transcriptional roles unresolved"]},{"year":2025,"claim":"To explain ZNF280A's transcriptional output, this study showed it interacts with CUX2 to enhance ACRV1 transcription and drive PI3K/AKT-linked glycolysis in ovarian cancer.","evidence":"Co-IP between ZNF280A and CUX2, promoter recruitment assay at ACRV1, metabolic assays, and pharmacological AKT/glycolysis rescue","pmids":["41338461"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal structural validation","Whether CUX2 partnership generalizes beyond ovarian cancer unknown"]},{"year":2025,"claim":"This work tested ZNF280A's influence on cell survival in melanoma, linking its loss to p53 upregulation, apoptosis, and cell cycle arrest.","evidence":"shRNA knockdown with Western blot for p53, flow cytometry for apoptosis and cell cycle, and functional assays in melanoma","pmids":["40251414"],"confidence":"Low","gaps":["Single method (Western blot) for p53 with limited mechanistic depth","No demonstration of direct regulation of p53","Not independently confirmed"]},{"year":null,"claim":"How ZNF280A's role in homologous-recombination resection mechanistically connects to its diverse oncogenic transcriptional and post-translational activities remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No unifying model linking DSB repair function to tumor-promoting effectors","DNA-binding specificity and direct transcriptional targets undefined","No structural characterization"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,4]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,4]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,4]}],"pathway":[{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[1,2,3,4]}],"complexes":[],"partners":["BLM","DNA2","CUX2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P59817","full_name":"Zinc finger protein 280A","aliases":["3'OY11.1","Suppressor of hairy wing homolog 1","Zinc finger protein 636"],"length_aa":542,"mass_kda":60.6,"function":"May function as a transcription factor","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P59817/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNF280A","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ZNF280A","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"adrenal gland","ntpm":1.3}],"url":"https://www.proteinatlas.org/search/ZNF280A"},"hgnc":{"alias_symbol":["3'OY11.1","ZNF636"],"prev_symbol":["ZNF280","SUHW1"]},"alphafold":{"accession":"P59817","domains":[{"cath_id":"-","chopping":"283-478","consensus_level":"high","plddt":89.8712,"start":283,"end":478}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P59817","model_url":"https://alphafold.ebi.ac.uk/files/AF-P59817-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P59817-F1-predicted_aligned_error_v6.png","plddt_mean":59.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNF280A","jax_strain_url":"https://www.jax.org/strain/search?query=ZNF280A"},"sequence":{"accession":"P59817","fasta_url":"https://rest.uniprot.org/uniprotkb/P59817.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P59817/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P59817"}},"corpus_meta":[{"pmid":"18984860","id":"PMC_18984860","title":"Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling.","date":"2008","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/18984860","citation_count":137,"is_preprint":false},{"pmid":"19027161","id":"PMC_19027161","title":"Array CGH analysis of chronic lymphocytic leukemia reveals frequent cryptic monoallelic and biallelic deletions of chromosome 22q11 that include the PRAME gene.","date":"2008","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/19027161","citation_count":44,"is_preprint":false},{"pmid":"33414445","id":"PMC_33414445","title":"ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/33414445","citation_count":22,"is_preprint":false},{"pmid":"30847384","id":"PMC_30847384","title":"ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer.","date":"2019","source":"Molecular therapy oncolytics","url":"https://pubmed.ncbi.nlm.nih.gov/30847384","citation_count":15,"is_preprint":false},{"pmid":"36876139","id":"PMC_36876139","title":"Comprehensive characterization of the embryonic factor LEUTX.","date":"2023","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/36876139","citation_count":14,"is_preprint":false},{"pmid":"36059657","id":"PMC_36059657","title":"Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36059657","citation_count":9,"is_preprint":false},{"pmid":"40523937","id":"PMC_40523937","title":"ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome.","date":"2025","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/40523937","citation_count":4,"is_preprint":false},{"pmid":"37345848","id":"PMC_37345848","title":"Knockdown of ZNF280A inhibits cell proliferation and promotes cell apoptosis of bladder cancer.","date":"2023","source":"Histology and histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/37345848","citation_count":3,"is_preprint":false},{"pmid":"40514799","id":"PMC_40514799","title":"ZNF280AY: a pseudogene on the ovine Y chromosome and its copy number variation associated with testicular size in Hu sheep.","date":"2025","source":"Journal of animal science","url":"https://pubmed.ncbi.nlm.nih.gov/40514799","citation_count":1,"is_preprint":false},{"pmid":"41338461","id":"PMC_41338461","title":"ZNF280A and ACRV1 enhance aerobic glycolysis and drive ovarian cancer progression via the PI3K/AKT signaling pathway.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41338461","citation_count":0,"is_preprint":false},{"pmid":"40251414","id":"PMC_40251414","title":"ZNF280A promotes malignant melanoma development through regulating cell proliferation, apoptosis, and cell cycle.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40251414","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7166,"output_tokens":1616,"usd":0.022869,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8422,"output_tokens":2397,"usd":0.051018,"stage2_stop_reason":"end_turn"},"total_usd":0.073887,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"ZNF280A is recruited to DNA double-strand break (DSB) sites and is essential for DSB repair by homologous recombination. Mechanistically, ZNF280A promotes long-range DNA-end resection by facilitating the recruitment of the BLM-DNA2 helicase-nuclease complex to DSB sites and enhancing the enzymatic activity of this complex at DNA damage sites. Loss of ZNF280A drives genomic instability and sensitivity to DNA-damaging agents.\",\n      \"method\": \"High-throughput microscopy with cDNA 'chromORFeome' library screen, loss-of-function experiments, recruitment assays to DSB sites, BLM-DNA2 complex recruitment and enzymatic activity assays, rescue by ZNF280A reintroduction in patient-derived cells\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mechanistic assays (enzymatic activity, complex recruitment), multiple orthogonal methods, genetic rescue in human patient-derived cells, single rigorous study\",\n      \"pmids\": [\"40523937\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C; downregulation of EIF3C in ZNF280A-overexpressed cells attenuated ZNF280A-induced tumor promotion, placing EIF3C as a downstream effector of ZNF280A.\",\n      \"method\": \"Gene expression profiling after ZNF280A knockdown, loss-of-function and overexpression in vitro and in vivo, epistasis rescue experiment (EIF3C knockdown in ZNF280A-overexpressed cells)\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — epistasis rescue experiment and expression profiling support pathway placement, single lab, multiple functional assays but no direct biochemical interaction demonstrated\",\n      \"pmids\": [\"33414445\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ZNF280A promotes colorectal cancer cell proliferation by inactivating the Hippo signaling pathway; silencing ZNF280A activated Hippo signaling and suppressed proliferation with G0/G1 arrest.\",\n      \"method\": \"Western blot and luciferase reporter assays for Hippo pathway activity, siRNA-mediated silencing, in vitro proliferation assays, in vivo xenograft\",\n      \"journal\": \"Molecular therapy oncolytics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — pathway placement by Western blot and luciferase assay, single lab, single study\",\n      \"pmids\": [\"30847384\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"ZNF280A knockdown promotes the ubiquitination and degradation of RPS14 in colorectal cancer cells, and RPS14 in turn regulates CRC development via the PI3K-Akt signaling pathway, establishing a ZNF280A/RPS14/PI3K-Akt axis.\",\n      \"method\": \"Loss-of-function (ZNF280A knockdown), ubiquitination assays, Western blot for RPS14 protein levels and PI3K-Akt pathway components, in vitro and in vivo functional assays\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — ubiquitination assay establishes downstream regulatory mechanism, single lab, single study\",\n      \"pmids\": [\"36059657\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZNF280A enhances ACRV1 transcription by interacting with the transcription factor CUX2 and facilitating CUX2 recruitment to the ACRV1 promoter; elevated ZNF280A or ACRV1 activates PI3K/AKT signaling and increases glycolytic enzyme expression (PKM2, LDHA), glucose uptake, lactate production, and ATP generation in ovarian cancer cells.\",\n      \"method\": \"Co-immunoprecipitation/interaction assays between ZNF280A and CUX2, chromatin recruitment assay to ACRV1 promoter, knockdown/overexpression functional assays, metabolic assays (glucose uptake, lactate, ATP, ECAR), pharmacological AKT/glycolysis inhibition rescue\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — Co-IP interaction and promoter recruitment assay with pharmacological rescue, single lab, single study\",\n      \"pmids\": [\"41338461\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZNF280A knockdown in malignant melanoma cells leads to increased apoptosis and cell cycle arrest associated with upregulation of p53 expression, suggesting ZNF280A regulates p53 levels in this context.\",\n      \"method\": \"shRNA-mediated knockdown, Western blot for p53, flow cytometry for apoptosis and cell cycle, in vitro and in vivo functional assays\",\n      \"journal\": \"Discover oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (Western blot for p53), limited mechanistic depth\",\n      \"pmids\": [\"40251414\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNF280A is a chromatin-associated zinc finger protein that functions primarily as a promoter of long-range DNA-end resection during homologous recombination by facilitating recruitment of the BLM-DNA2 helicase-nuclease complex to double-strand break sites; in cancer contexts it also acts as a transcriptional regulator that drives tumor progression through downstream effectors including EIF3C, RPS14/PI3K-Akt, and CUX2-ACRV1-PI3K/AKT axes, and modulates the Hippo signaling pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNF280A is a chromatin-associated zinc finger protein that operates at the interface of genome maintenance and oncogenic signaling [#0, #1]. Its best-defined molecular function is in DNA double-strand break repair: ZNF280A is recruited to break sites and promotes long-range DNA-end resection during homologous recombination by facilitating recruitment of the BLM-DNA2 helicase-nuclease complex and enhancing its enzymatic activity, such that loss of ZNF280A causes genomic instability and sensitivity to DNA-damaging agents [#0]. In cancer settings ZNF280A behaves as a tumor-promoting factor that acts through multiple downstream effectors: it sustains EIF3C expression to drive lung adenocarcinoma [#1], stabilizes RPS14 against ubiquitin-mediated degradation to engage PI3K-Akt signaling in colorectal cancer [#3], and interacts with the transcription factor CUX2 to enhance ACRV1 transcription, activating PI3K/AKT signaling and glycolytic metabolism in ovarian cancer [#4]. It additionally inactivates Hippo signaling to support proliferation [#2]. Beyond these contexts, the structural basis of ZNF280A's DNA/chromatin association and its direct transcriptional targets have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Whether ZNF280A had any role in tumor cell proliferation was unknown; this work placed it as a driver of colorectal cancer growth acting through Hippo pathway inactivation.\",\n      \"evidence\": \"siRNA silencing with luciferase reporter and Western blot for Hippo activity, proliferation assays, and xenografts in colorectal cancer\",\n      \"pmids\": [\"30847384\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct molecular interaction linking ZNF280A to Hippo components\", \"Mechanism of pathway regulation (transcriptional vs post-translational) undefined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To identify ZNF280A's pro-tumor effectors, this study established EIF3C as a downstream mediator required for ZNF280A-induced lung adenocarcinoma promotion.\",\n      \"evidence\": \"Expression profiling after knockdown plus epistasis rescue (EIF3C knockdown in ZNF280A-overexpressing cells) in vitro and in vivo\",\n      \"pmids\": [\"33414445\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No demonstration that ZNF280A binds the EIF3C locus directly\", \"Whether regulation is transcriptional remains unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Building on cancer roles, this work added a post-translational axis whereby ZNF280A protects RPS14 from ubiquitin-mediated degradation to engage PI3K-Akt signaling.\",\n      \"evidence\": \"Knockdown with ubiquitination assays and Western blot for RPS14 and PI3K-Akt components, functional assays in colorectal cancer cells\",\n      \"pmids\": [\"36059657\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which ZNF280A controls RPS14 ubiquitination is unknown\", \"No identified E3 ligase or direct binding\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The molecular function of ZNF280A had remained obscure; a chromORFeome screen revealed it is a DSB repair factor that promotes long-range resection via the BLM-DNA2 complex.\",\n      \"evidence\": \"High-throughput microscopy screen, recruitment assays to DSB sites, BLM-DNA2 complex recruitment and enzymatic activity assays, and rescue in patient-derived cells\",\n      \"pmids\": [\"40523937\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of ZNF280A or its DNA/chromatin contacts\", \"Direct physical interaction interface with BLM-DNA2 not mapped\", \"Relationship between resection role and oncogenic transcriptional roles unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To explain ZNF280A's transcriptional output, this study showed it interacts with CUX2 to enhance ACRV1 transcription and drive PI3K/AKT-linked glycolysis in ovarian cancer.\",\n      \"evidence\": \"Co-IP between ZNF280A and CUX2, promoter recruitment assay at ACRV1, metabolic assays, and pharmacological AKT/glycolysis rescue\",\n      \"pmids\": [\"41338461\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP without reciprocal structural validation\", \"Whether CUX2 partnership generalizes beyond ovarian cancer unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"This work tested ZNF280A's influence on cell survival in melanoma, linking its loss to p53 upregulation, apoptosis, and cell cycle arrest.\",\n      \"evidence\": \"shRNA knockdown with Western blot for p53, flow cytometry for apoptosis and cell cycle, and functional assays in melanoma\",\n      \"pmids\": [\"40251414\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method (Western blot) for p53 with limited mechanistic depth\", \"No demonstration of direct regulation of p53\", \"Not independently confirmed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ZNF280A's role in homologous-recombination resection mechanistically connects to its diverse oncogenic transcriptional and post-translational activities remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No unifying model linking DSB repair function to tumor-promoting effectors\", \"DNA-binding specificity and direct transcriptional targets undefined\", \"No structural characterization\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [1, 2, 3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"BLM\", \"DNA2\", \"CUX2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}