{"gene":"TBPL1","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2001,"finding":"TLF/TRF2 (TBPL1) is essential for late spermiogenesis in mice; targeted knockout causes complete arrest at step 7 round spermatids with apoptosis, while spermatogonia and spermatocytes develop normally. Several spermiogenesis genes transcribed in late round spermatids require TLF for expression.","method":"Homologous recombination knockout in mice, histology, gene expression analysis","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with specific cellular phenotype (step 7 arrest), replicated across multiple analyses, published in peer-reviewed journal","pmids":["11463376"],"is_preprint":false},{"year":2002,"finding":"TLF/TRF2 (TBPL1) is required for heterochromatic chromocenter formation and acrosome formation in early round spermatids; TLF-deficient mice show fragmentation of the chromocenter (the condensed HP1-containing centromeric heterochromatin structure), identified as the likely primary cause of spermatogenic failure. TLF and TBP differ dramatically in temporal expression pattern and intracellular localization.","method":"Analysis of TLF-null mice, immunofluorescence for HP1 and chromocenter structure, comparative TBP/TLF localization studies","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with specific subcellular phenotype (chromocenter fragmentation), multiple orthogonal methods (immunostaining, histology), independent replication of KO model","pmids":["11861477"],"is_preprint":false},{"year":2003,"finding":"TLP/TRF2/TLF (TBPL1) localizes predominantly to the cytoplasm in mammalian cells (NIH3T3); only ~4% of total TLP molecules reside in the nucleus. TLP binds TFIIA with ~7-fold higher affinity (Kd=1.5 nM) than TBP (Kd=10 nM), and the TLP-TFIIA complex dissociates ~18-fold more slowly. TLP forms dimers and trimers that are inhibited by TFIIA. TFIIA-binding ability of TLP (requiring residues Ala-32, Leu-33, Asn-37, Arg-52, Lys-53, Lys-78, Arg-86) is required for its characteristic cytoplasmic localization; TFIIA-binding-defective mutants accumulate in the nucleus.","method":"Biophysical binding assays (surface plasmon resonance/kinetics), immunostaining, stable cell lines expressing mutant TLP, subcellular fractionation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — quantitative biophysical measurements, mutagenesis identifying specific residues, functional localization consequence, multiple orthogonal methods in one study","pmids":["14570910"],"is_preprint":false},{"year":2003,"finding":"TLP/TRF2/TLF (TBPL1) functions as a negative regulator of the G2/M cell cycle phase; TLP-null chicken DT40 cells show accelerated G2 progression (~20% elevated cell cycle rate). TLP translocates from cytoplasm to nucleus specifically at G2 phase. Ectopic nuclear TLP increases G2/M and apoptotic cell fractions. TLP-null cells have a defective G2 checkpoint response to UV and MMS, and TLP translocates to the nucleus rapidly (within 15 min) after stress. These effects are p53-independent.","method":"TLP knockout in chicken DT40 cells, cell cycle analysis by flow cytometry, stress (UV, MMS) challenge, nuclear localization signal (NLS)-TLP overexpression, gene expression analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cell cycle phenotype plus rescue by ectopic expression, multiple orthogonal methods (flow cytometry, stress assays, localization)","pmids":["12773555"],"is_preprint":false},{"year":2003,"finding":"TLP/TRF2/TLF (TBPL1) stimulates transcription from TATA-less promoters (terminal deoxynucleotidyl transferase, TdT) while repressing TATA-containing promoters (adenovirus MLP, E1B). TFIIA-binding ability of TLP is required for activation of TATA-less promoters but suppresses TLP-mediated repression of TATA promoters. TdT promoter activity is lower in TLP-null DT40 cells and rescued by ectopic TLP; insertion of a TATA element abolishes TLP-mediated activation.","method":"Transient reporter assays, TLP-null DT40 cells with rescue, TFIIA-binding mutant TLP constructs, promoter insertion mutagenesis","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro and cell-based reporter assays plus mutagenesis plus genetic rescue, multiple orthogonal methods","pmids":["12682363"],"is_preprint":false},{"year":2001,"finding":"Artificially promoter-recruited TLP/TLF/TRF2 (TBPL1), fused to Gal4 DNA-binding domain, stimulates basal transcription from both TATA-containing and TATA-less class II promoters in vivo. Stimulation is less TATA-dependent than TBP. Truncation from either terminus or amino acid substitutions at positions equivalent to TBP functional residues abolishes this activity.","method":"Gal4-TLP fusion transient transfection reporter assay, deletion and point mutant analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro/cell-based reconstitution with mutagenesis, single lab, partial mechanistic follow-up","pmids":["11453637"],"is_preprint":false},{"year":2005,"finding":"Human TLF/TRF2 (TBPL1) activates transcription of the NF1 gene by directly binding the NF1 promoter via a TLF-TFIIA complex, and reciprocally inhibits transcription from the TATA-containing c-fos promoter by sequestering TFIIA. TBP acts in the opposite manner: activating c-fos and inhibiting NF1. TLF knockout in mice reduces NF1 mRNA levels, confirming in vivo relevance.","method":"Overexpression in cells (NF1 mRNA quantification), in vitro EMSA/binding with purified TLF-TFIIA, promoter reporter assays, TLF KO mouse analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro binding with purified proteins, cell-based reporter assays, and in vivo KO confirmation provide multiple orthogonal methods","pmids":["15767669"],"is_preprint":false},{"year":2014,"finding":"miR-133b directly targets the 3'-UTR of TBPL1 mRNA, negatively regulating TBPL1 protein expression in colorectal cancer cells. TBPL1 knockdown reduces proliferation of CRC cells, establishing a functional role for TBPL1 in supporting cancer cell proliferation.","method":"Luciferase 3'-UTR reporter assay with wild-type and mutant TBPL1 3'-UTR, miR-133b mimic/inhibitor transfection, siRNA knockdown, Western blotting, MTT proliferation assay","journal":"Asian Pacific journal of cancer prevention : APJCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter plus Western blot plus functional proliferation assay, single lab with two orthogonal methods validating miRNA-target relationship","pmids":["24870791"],"is_preprint":false},{"year":2015,"finding":"miR-18a directly targets the 3'-UTR of TBPL1 mRNA to inhibit TBPL1 expression, reducing proliferation, invasion, and migration of colorectal cancer cells.","method":"Luciferase 3'-UTR reporter assay, RT-qPCR, Western blotting, MTT assay, cell invasion and wound-healing assay","journal":"Molecular medicine reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter plus Western blot plus multiple functional assays, single lab, two orthogonal mechanistic methods","pmids":["26398009"],"is_preprint":false},{"year":2022,"finding":"C-MYC transcriptionally activates miR-9-5p, which in turn negatively regulates TBPL1 expression; this C-MYC→miR-9-5p⊣TBPL1 axis promotes pulmonary fibroblast proliferation and differentiation, driving idiopathic pulmonary fibrosis. Inhibition of C-MYC restores TBPL1 expression and suppresses fibrosis.","method":"ChIP assay (C-MYC binding to miR-9-5p promoter), dual luciferase reporter assay (miR-9-5p targeting TBPL1 3'-UTR), siRNA/inhibitor experiments in cells and bleomycin mouse model, RT-qPCR, Western blot","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus luciferase reporter plus in vivo mouse model, single lab with multiple orthogonal methods","pmids":["35122989"],"is_preprint":false},{"year":2024,"finding":"TBPL1 localizes to nucleoli and binds TCT motifs at intergenic spacer (IGS) regions of rDNA, where it drives both RNA Pol II and RNA Pol I activity. TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. TBPL1 is part of the nucleolar Pol II interactome alongside PAF1.","method":"Compartment-enriched proximity-dependent biotin identification (compBioID), ChIP, RNA-seq, nucleolar fractionation, loss-of-function (TBPL1 depletion) with nucleolar phenotype readout","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — proximity proteomics plus ChIP plus loss-of-function with defined nucleolar phenotype, multiple orthogonal methods in a single rigorous study","pmids":["39505901"],"is_preprint":false},{"year":2025,"finding":"TBPL1 knockout in breast cancer cell lines (T47D, SKBR3, MDA-MB-231) via CRISPR/Cas9 alters transcriptome signatures affecting genes involved in cell migration, proliferation, anti-apoptosis, and metastasis. TBPL1 loss also affects cell morphology and growth properties, and TBPL1 is overexpressed in these cancer cell lines relative to normal breast cells.","method":"CRISPR/Cas9 knockout, RNA-seq transcriptome profiling, in vivo tumor assay (MDA-MB-231)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean CRISPR KO with transcriptome-level readout but single lab, single paper with limited mechanistic depth in abstract","pmids":["41152284"],"is_preprint":false}],"current_model":"TBPL1 (TLF/TRF2/TLP) is a TBP-related transcription factor that preferentially binds TATA-less promoters via TCT motifs and forms a highly stable complex with TFIIA (Kd ~1.5 nM), using this interaction to activate TATA-less target genes (including NF1, TdT, and rDNA IGS loci) while repressing TATA-containing promoters by sequestering TFIIA; it resides predominantly in the cytoplasm in somatic cells but translocates to the nucleus at G2 phase to negatively regulate cell cycle progression and mediate a p53-independent G2 DNA damage checkpoint, and is essential in vivo for chromocenter integrity, acrosome formation, and late spermiogenesis, as well as for nucleolar organization and rRNA biogenesis through its role in IGS Pol II/Pol I regulation."},"narrative":{"mechanistic_narrative":"TBPL1 (TLF/TRF2/TLP) is a TBP-related factor that controls a distinct mode of class II transcription initiation, selectively activating TATA-less promoters while repressing TATA-containing promoters [PMID:12682363, PMID:15767669]. Its defining biochemical property is an unusually stable, high-affinity association with TFIIA (Kd ~1.5 nM, with ~18-fold slower dissociation than TBP), and this TFIIA-binding activity both enables activation of TATA-less targets such as TdT and NF1 and underlies repression of TATA promoters such as c-fos by TFIIA sequestration [PMID:14570910, PMID:12682363, PMID:15767669]. TFIIA engagement also dictates TBPL1 subcellular behavior: most TBPL1 is cytoplasmic in somatic cells, and TFIIA-binding-defective mutants instead accumulate in the nucleus [PMID:14570910]. TBPL1 translocates to the nucleus at G2 phase and after genotoxic stress to act as a p53-independent negative regulator of G2/M progression and the G2 DNA-damage checkpoint [PMID:12773555]. At the rDNA intergenic spacer, nucleolar TBPL1 binds TCT motifs to drive both Pol II and Pol I activity, and its loss disrupts nucleolar organization and rRNA biogenesis [PMID:39505901]. In vivo, TBPL1 is essential for late spermiogenesis, with knockout causing chromocenter fragmentation, defective acrosome formation, and arrest of round spermatids [PMID:11463376, PMID:11861477]. Multiple microRNAs converge on the TBPL1 3'-UTR to restrain its expression in cancer and fibrosis, where TBPL1 supports proliferative and metastatic phenotypes [PMID:24870791, PMID:35122989, PMID:41152284].","teleology":[{"year":2001,"claim":"Established that TBPL1 has an essential, stage-specific developmental function distinct from the general transcription factor TBP, by showing it is required for a defined step of spermatogenesis.","evidence":"Homologous-recombination knockout in mice with histology and gene expression analysis","pmids":["11463376"],"confidence":"High","gaps":["Direct promoter targets driving the step-7 arrest not defined","Did not establish the molecular mechanism linking TBPL1 loss to apoptosis"]},{"year":2002,"claim":"Refined the spermatogenic defect to a primary structural cause, linking TBPL1 to heterochromatin organization rather than only gene expression.","evidence":"Analysis of TLF-null mice with HP1 immunofluorescence and chromocenter/acrosome readouts","pmids":["11861477"],"confidence":"High","gaps":["How TBPL1 promotes chromocenter integrity mechanistically is unresolved","Connection between heterochromatin role and transcriptional role not bridged"]},{"year":2003,"claim":"Defined the central biochemical mechanism — a high-affinity, kinetically stable TBPL1-TFIIA complex — and showed this interaction governs TBPL1's cytoplasmic localization.","evidence":"Surface plasmon resonance kinetics, mutagenesis of TFIIA-binding residues, immunostaining and fractionation in NIH3T3 cells","pmids":["14570910"],"confidence":"High","gaps":["Functional purpose of cytoplasmic sequestration not fully explained","Trigger that releases TBPL1 from TFIIA for nuclear entry not identified"]},{"year":2003,"claim":"Showed TBPL1 acts as a p53-independent negative regulator of G2/M and a G2 DNA-damage checkpoint factor, coupling its regulated nuclear translocation to cell cycle control.","evidence":"TLP knockout in chicken DT40 cells, flow cytometry, UV/MMS stress challenge, and NLS-TLP overexpression","pmids":["12773555"],"confidence":"High","gaps":["Nuclear targets of TBPL1 during the checkpoint not identified","Signal driving rapid stress-induced translocation unknown"]},{"year":2003,"claim":"Demonstrated the dual promoter logic of TBPL1 — activation of TATA-less and repression of TATA-containing promoters — and that TFIIA-binding determines which mode dominates.","evidence":"Reporter assays in TLP-null DT40 cells with rescue, TFIIA-binding mutants, and TATA-insertion mutagenesis at the TdT promoter","pmids":["12682363","11453637"],"confidence":"High","gaps":["Genome-wide promoter repertoire not mapped","Whether activation requires additional co-factors beyond TFIIA unclear"]},{"year":2005,"claim":"Identified specific natural target genes (NF1 activated, c-fos repressed) and confirmed in vivo relevance, contrasting TBPL1 and TBP as reciprocal regulators acting through TFIIA.","evidence":"EMSA with purified TLF-TFIIA, promoter reporter assays, NF1 mRNA quantification, and TLF-KO mouse analysis","pmids":["15767669"],"confidence":"High","gaps":["Breadth of TATA-less target genes in vivo not defined","Sequence determinants of TBPL1 promoter recognition not resolved here"]},{"year":2014,"claim":"Opened a cancer-relevant regulatory dimension by showing TBPL1 is post-transcriptionally repressed by a microRNA and supports tumor cell proliferation.","evidence":"miR-133b 3'-UTR luciferase reporter, mimic/inhibitor and siRNA experiments, and MTT proliferation assay in colorectal cancer cells","pmids":["24870791"],"confidence":"Medium","gaps":["Downstream transcriptional program mediating proliferation not defined","Single cancer-type context"]},{"year":2015,"claim":"Reinforced microRNA control of TBPL1 with a second regulator and extended its phenotypic contribution to invasion and migration.","evidence":"miR-18a 3'-UTR luciferase reporter, RT-qPCR, Western blot, MTT, invasion and wound-healing assays in colorectal cancer cells","pmids":["26398009"],"confidence":"Medium","gaps":["Mechanistic link from TBPL1 to migration/invasion not established","No in vivo confirmation"]},{"year":2022,"claim":"Placed TBPL1 in a defined disease signaling axis (C-MYC -> miR-9-5p -| TBPL1) in pulmonary fibrosis, indicating its expression is tuned by upstream oncogenic transcription factors.","evidence":"ChIP for C-MYC, dual-luciferase reporter for miR-9-5p targeting TBPL1, siRNA/inhibitor studies, and bleomycin mouse model","pmids":["35122989"],"confidence":"Medium","gaps":["Whether TBPL1's transcriptional activity mediates the fibrotic phenotype not shown","Direct TBPL1 target genes in fibroblasts unidentified"]},{"year":2024,"claim":"Established a nucleolar function, showing TBPL1 binds TCT motifs at rDNA intergenic spacers to coordinate Pol II and Pol I activity for rRNA biogenesis.","evidence":"Compartment-enriched proximity biotinylation (compBioID), ChIP, RNA-seq, nucleolar fractionation, and depletion phenotyping","pmids":["39505901"],"confidence":"High","gaps":["Mechanism by which TBPL1 couples Pol II to Pol I at IGS not detailed","Functional role of PAF1 association with TBPL1 not dissected"]},{"year":2025,"claim":"Connected TBPL1 to breast cancer biology, showing knockout reshapes transcriptomes governing migration, proliferation and metastasis and that TBPL1 is overexpressed in tumor cells.","evidence":"CRISPR/Cas9 knockout, RNA-seq, and in vivo tumor assay across multiple breast cancer cell lines","pmids":["41152284"],"confidence":"Medium","gaps":["Direct promoter targets among the altered genes not identified","Limited mechanistic depth beyond transcriptome-level association"]},{"year":null,"claim":"How TBPL1's transcriptional/TFIIA-sequestering activity, its cell-cycle checkpoint role, its nucleolar rDNA function, and its heterochromatin/spermiogenesis requirement integrate into a unified mechanism remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genome-wide map unifying TBPL1 binding sites across promoters, IGS, and heterochromatin","Signal controlling regulated cytoplasm-to-nucleus translocation unknown","Mechanistic basis of chromocenter integrity role uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[4,6,10]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[6,10]},{"term_id":"GO:0140223","term_label":"general transcription initiation factor activity","supporting_discovery_ids":[4,5]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,6]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2,3]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[10]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[4,6,10]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[10]}],"complexes":[],"partners":["GTF2A1","PAF1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P62380","full_name":"TATA box-binding protein-like 1","aliases":["21 kDa TBP-like protein","Second TBP of unique DNA protein","STUD","TATA box-binding protein-related factor 2","TBP-related factor 2","TBP-like factor","TBP-related protein"],"length_aa":186,"mass_kda":20.9,"function":"Part of a specialized transcription system that mediates the transcription of most ribosomal proteins through the 5'-TCT-3' motif which is a core promoter element at these genes. Seems to also mediate the transcription of NF1. Does not bind the TATA box","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/P62380/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TBPL1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TBPL1","total_profiled":1310},"omim":[{"mim_id":"605521","title":"TATA BOX-BINDING PROTEIN-LIKE PROTEIN 1; TBPL1","url":"https://www.omim.org/entry/605521"},{"mim_id":"600075","title":"TATA BOX-BINDING PROTEIN; TBP","url":"https://www.omim.org/entry/600075"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":118.4}],"url":"https://www.proteinatlas.org/search/TBPL1"},"hgnc":{"alias_symbol":["TLP","STUD","TRF2","TLF"],"prev_symbol":[]},"alphafold":{"accession":"P62380","domains":[{"cath_id":"3.30.310.10","chopping":"16-103","consensus_level":"high","plddt":97.7719,"start":16,"end":103},{"cath_id":"3.30.310.10","chopping":"111-180","consensus_level":"high","plddt":97.4376,"start":111,"end":180}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P62380","model_url":"https://alphafold.ebi.ac.uk/files/AF-P62380-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P62380-F1-predicted_aligned_error_v6.png","plddt_mean":95.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TBPL1","jax_strain_url":"https://www.jax.org/strain/search?query=TBPL1"},"sequence":{"accession":"P62380","fasta_url":"https://rest.uniprot.org/uniprotkb/P62380.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P62380/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P62380"}},"corpus_meta":[{"pmid":"11463376","id":"PMC_11463376","title":"Late 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tierarztliche Wochenschrift","url":"https://pubmed.ncbi.nlm.nih.gov/14964126","citation_count":3,"is_preprint":false},{"pmid":"6773216","id":"PMC_6773216","title":"[Estimation of the heritability coefficient of stud fertility].","date":"1980","source":"Veterinarni medicina","url":"https://pubmed.ncbi.nlm.nih.gov/6773216","citation_count":3,"is_preprint":false},{"pmid":"25108107","id":"PMC_25108107","title":"A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF.","date":"2014","source":"Journal of molecular graphics & modelling","url":"https://pubmed.ncbi.nlm.nih.gov/25108107","citation_count":2,"is_preprint":false},{"pmid":"25379217","id":"PMC_25379217","title":"Symptom persistence and memory performance in posttraumatic stress disorder: a gene x environment pilot stud.","date":"2012","source":"Behavioral sciences (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/25379217","citation_count":2,"is_preprint":false},{"pmid":"21446190","id":"PMC_21446190","title":"[Association of the DGAT1 gene polymorphism in stud bulls with milk productivity in cows].","date":"2011","source":"Genetika","url":"https://pubmed.ncbi.nlm.nih.gov/21446190","citation_count":2,"is_preprint":false},{"pmid":"36676439","id":"PMC_36676439","title":"Experimental and Theoretical Study on the Fatigue Crack Propagation in Stud Shear Connectors.","date":"2023","source":"Materials (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/36676439","citation_count":1,"is_preprint":false},{"pmid":"41497244","id":"PMC_41497244","title":"Ureter reconstruction using a biotube in a canine model: A pilot stud.","date":"2025","source":"Journal of stem cells & regenerative medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41497244","citation_count":1,"is_preprint":false},{"pmid":"22405894","id":"PMC_22405894","title":"Differential plasticity of microglial cells in the rostrocaudal neuraxis of the accessory olfactory bulb of female mice following mating and stud male exposure.","date":"2012","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/22405894","citation_count":1,"is_preprint":false},{"pmid":"41152284","id":"PMC_41152284","title":"RNA-seq analysis of wild-type and mutated TBPL1 gene in breast cancer cells lines through CRISPR/Cas9 approach reveals novel molecular signatures.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41152284","citation_count":0,"is_preprint":false},{"pmid":"4353840","id":"PMC_4353840","title":"Diagnosis of mixed infections with myxovirus influenzae A equi 2 and herpes virus equi 1 among Danish stud horses.","date":"1973","source":"Acta veterinaria Scandinavica","url":"https://pubmed.ncbi.nlm.nih.gov/4353840","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.06.21.600114","title":"Mono-allelic epigenetic regulation of bi-directional silencing of RNA Polymerase II polycistronic transcription initiation in  <i>Trypanosoma brucei</i>","date":"2024-06-22","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.21.600114","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.14.688439","title":"Paternal over- and under-nutrition program fetal and placental development in a sex-specific manner in mice","date":"2025-11-14","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.14.688439","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":22509,"output_tokens":3471,"usd":0.059796,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10999,"output_tokens":3811,"usd":0.075135,"stage2_stop_reason":"end_turn"},"total_usd":0.134931,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"TLF/TRF2 (TBPL1) is essential for late spermiogenesis in mice; targeted knockout causes complete arrest at step 7 round spermatids with apoptosis, while spermatogonia and spermatocytes develop normally. Several spermiogenesis genes transcribed in late round spermatids require TLF for expression.\",\n      \"method\": \"Homologous recombination knockout in mice, histology, gene expression analysis\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with specific cellular phenotype (step 7 arrest), replicated across multiple analyses, published in peer-reviewed journal\",\n      \"pmids\": [\"11463376\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"TLF/TRF2 (TBPL1) is required for heterochromatic chromocenter formation and acrosome formation in early round spermatids; TLF-deficient mice show fragmentation of the chromocenter (the condensed HP1-containing centromeric heterochromatin structure), identified as the likely primary cause of spermatogenic failure. TLF and TBP differ dramatically in temporal expression pattern and intracellular localization.\",\n      \"method\": \"Analysis of TLF-null mice, immunofluorescence for HP1 and chromocenter structure, comparative TBP/TLF localization studies\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with specific subcellular phenotype (chromocenter fragmentation), multiple orthogonal methods (immunostaining, histology), independent replication of KO model\",\n      \"pmids\": [\"11861477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TLP/TRF2/TLF (TBPL1) localizes predominantly to the cytoplasm in mammalian cells (NIH3T3); only ~4% of total TLP molecules reside in the nucleus. TLP binds TFIIA with ~7-fold higher affinity (Kd=1.5 nM) than TBP (Kd=10 nM), and the TLP-TFIIA complex dissociates ~18-fold more slowly. TLP forms dimers and trimers that are inhibited by TFIIA. TFIIA-binding ability of TLP (requiring residues Ala-32, Leu-33, Asn-37, Arg-52, Lys-53, Lys-78, Arg-86) is required for its characteristic cytoplasmic localization; TFIIA-binding-defective mutants accumulate in the nucleus.\",\n      \"method\": \"Biophysical binding assays (surface plasmon resonance/kinetics), immunostaining, stable cell lines expressing mutant TLP, subcellular fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — quantitative biophysical measurements, mutagenesis identifying specific residues, functional localization consequence, multiple orthogonal methods in one study\",\n      \"pmids\": [\"14570910\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TLP/TRF2/TLF (TBPL1) functions as a negative regulator of the G2/M cell cycle phase; TLP-null chicken DT40 cells show accelerated G2 progression (~20% elevated cell cycle rate). TLP translocates from cytoplasm to nucleus specifically at G2 phase. Ectopic nuclear TLP increases G2/M and apoptotic cell fractions. TLP-null cells have a defective G2 checkpoint response to UV and MMS, and TLP translocates to the nucleus rapidly (within 15 min) after stress. These effects are p53-independent.\",\n      \"method\": \"TLP knockout in chicken DT40 cells, cell cycle analysis by flow cytometry, stress (UV, MMS) challenge, nuclear localization signal (NLS)-TLP overexpression, gene expression analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cell cycle phenotype plus rescue by ectopic expression, multiple orthogonal methods (flow cytometry, stress assays, localization)\",\n      \"pmids\": [\"12773555\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TLP/TRF2/TLF (TBPL1) stimulates transcription from TATA-less promoters (terminal deoxynucleotidyl transferase, TdT) while repressing TATA-containing promoters (adenovirus MLP, E1B). TFIIA-binding ability of TLP is required for activation of TATA-less promoters but suppresses TLP-mediated repression of TATA promoters. TdT promoter activity is lower in TLP-null DT40 cells and rescued by ectopic TLP; insertion of a TATA element abolishes TLP-mediated activation.\",\n      \"method\": \"Transient reporter assays, TLP-null DT40 cells with rescue, TFIIA-binding mutant TLP constructs, promoter insertion mutagenesis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro and cell-based reporter assays plus mutagenesis plus genetic rescue, multiple orthogonal methods\",\n      \"pmids\": [\"12682363\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Artificially promoter-recruited TLP/TLF/TRF2 (TBPL1), fused to Gal4 DNA-binding domain, stimulates basal transcription from both TATA-containing and TATA-less class II promoters in vivo. Stimulation is less TATA-dependent than TBP. Truncation from either terminus or amino acid substitutions at positions equivalent to TBP functional residues abolishes this activity.\",\n      \"method\": \"Gal4-TLP fusion transient transfection reporter assay, deletion and point mutant analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro/cell-based reconstitution with mutagenesis, single lab, partial mechanistic follow-up\",\n      \"pmids\": [\"11453637\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Human TLF/TRF2 (TBPL1) activates transcription of the NF1 gene by directly binding the NF1 promoter via a TLF-TFIIA complex, and reciprocally inhibits transcription from the TATA-containing c-fos promoter by sequestering TFIIA. TBP acts in the opposite manner: activating c-fos and inhibiting NF1. TLF knockout in mice reduces NF1 mRNA levels, confirming in vivo relevance.\",\n      \"method\": \"Overexpression in cells (NF1 mRNA quantification), in vitro EMSA/binding with purified TLF-TFIIA, promoter reporter assays, TLF KO mouse analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro binding with purified proteins, cell-based reporter assays, and in vivo KO confirmation provide multiple orthogonal methods\",\n      \"pmids\": [\"15767669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"miR-133b directly targets the 3'-UTR of TBPL1 mRNA, negatively regulating TBPL1 protein expression in colorectal cancer cells. TBPL1 knockdown reduces proliferation of CRC cells, establishing a functional role for TBPL1 in supporting cancer cell proliferation.\",\n      \"method\": \"Luciferase 3'-UTR reporter assay with wild-type and mutant TBPL1 3'-UTR, miR-133b mimic/inhibitor transfection, siRNA knockdown, Western blotting, MTT proliferation assay\",\n      \"journal\": \"Asian Pacific journal of cancer prevention : APJCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter plus Western blot plus functional proliferation assay, single lab with two orthogonal methods validating miRNA-target relationship\",\n      \"pmids\": [\"24870791\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"miR-18a directly targets the 3'-UTR of TBPL1 mRNA to inhibit TBPL1 expression, reducing proliferation, invasion, and migration of colorectal cancer cells.\",\n      \"method\": \"Luciferase 3'-UTR reporter assay, RT-qPCR, Western blotting, MTT assay, cell invasion and wound-healing assay\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter plus Western blot plus multiple functional assays, single lab, two orthogonal mechanistic methods\",\n      \"pmids\": [\"26398009\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"C-MYC transcriptionally activates miR-9-5p, which in turn negatively regulates TBPL1 expression; this C-MYC→miR-9-5p⊣TBPL1 axis promotes pulmonary fibroblast proliferation and differentiation, driving idiopathic pulmonary fibrosis. Inhibition of C-MYC restores TBPL1 expression and suppresses fibrosis.\",\n      \"method\": \"ChIP assay (C-MYC binding to miR-9-5p promoter), dual luciferase reporter assay (miR-9-5p targeting TBPL1 3'-UTR), siRNA/inhibitor experiments in cells and bleomycin mouse model, RT-qPCR, Western blot\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus luciferase reporter plus in vivo mouse model, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"35122989\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TBPL1 localizes to nucleoli and binds TCT motifs at intergenic spacer (IGS) regions of rDNA, where it drives both RNA Pol II and RNA Pol I activity. TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. TBPL1 is part of the nucleolar Pol II interactome alongside PAF1.\",\n      \"method\": \"Compartment-enriched proximity-dependent biotin identification (compBioID), ChIP, RNA-seq, nucleolar fractionation, loss-of-function (TBPL1 depletion) with nucleolar phenotype readout\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — proximity proteomics plus ChIP plus loss-of-function with defined nucleolar phenotype, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"39505901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TBPL1 knockout in breast cancer cell lines (T47D, SKBR3, MDA-MB-231) via CRISPR/Cas9 alters transcriptome signatures affecting genes involved in cell migration, proliferation, anti-apoptosis, and metastasis. TBPL1 loss also affects cell morphology and growth properties, and TBPL1 is overexpressed in these cancer cell lines relative to normal breast cells.\",\n      \"method\": \"CRISPR/Cas9 knockout, RNA-seq transcriptome profiling, in vivo tumor assay (MDA-MB-231)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean CRISPR KO with transcriptome-level readout but single lab, single paper with limited mechanistic depth in abstract\",\n      \"pmids\": [\"41152284\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TBPL1 (TLF/TRF2/TLP) is a TBP-related transcription factor that preferentially binds TATA-less promoters via TCT motifs and forms a highly stable complex with TFIIA (Kd ~1.5 nM), using this interaction to activate TATA-less target genes (including NF1, TdT, and rDNA IGS loci) while repressing TATA-containing promoters by sequestering TFIIA; it resides predominantly in the cytoplasm in somatic cells but translocates to the nucleus at G2 phase to negatively regulate cell cycle progression and mediate a p53-independent G2 DNA damage checkpoint, and is essential in vivo for chromocenter integrity, acrosome formation, and late spermiogenesis, as well as for nucleolar organization and rRNA biogenesis through its role in IGS Pol II/Pol I regulation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TBPL1 (TLF/TRF2/TLP) is a TBP-related factor that controls a distinct mode of class II transcription initiation, selectively activating TATA-less promoters while repressing TATA-containing promoters [#4, #6]. Its defining biochemical property is an unusually stable, high-affinity association with TFIIA (Kd ~1.5 nM, with ~18-fold slower dissociation than TBP), and this TFIIA-binding activity both enables activation of TATA-less targets such as TdT and NF1 and underlies repression of TATA promoters such as c-fos by TFIIA sequestration [#2, #4, #6]. TFIIA engagement also dictates TBPL1 subcellular behavior: most TBPL1 is cytoplasmic in somatic cells, and TFIIA-binding-defective mutants instead accumulate in the nucleus [#2]. TBPL1 translocates to the nucleus at G2 phase and after genotoxic stress to act as a p53-independent negative regulator of G2/M progression and the G2 DNA-damage checkpoint [#3]. At the rDNA intergenic spacer, nucleolar TBPL1 binds TCT motifs to drive both Pol II and Pol I activity, and its loss disrupts nucleolar organization and rRNA biogenesis [#10]. In vivo, TBPL1 is essential for late spermiogenesis, with knockout causing chromocenter fragmentation, defective acrosome formation, and arrest of round spermatids [#0, #1]. Multiple microRNAs converge on the TBPL1 3'-UTR to restrain its expression in cancer and fibrosis, where TBPL1 supports proliferative and metastatic phenotypes [#7, #9, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established that TBPL1 has an essential, stage-specific developmental function distinct from the general transcription factor TBP, by showing it is required for a defined step of spermatogenesis.\",\n      \"evidence\": \"Homologous-recombination knockout in mice with histology and gene expression analysis\",\n      \"pmids\": [\"11463376\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct promoter targets driving the step-7 arrest not defined\", \"Did not establish the molecular mechanism linking TBPL1 loss to apoptosis\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Refined the spermatogenic defect to a primary structural cause, linking TBPL1 to heterochromatin organization rather than only gene expression.\",\n      \"evidence\": \"Analysis of TLF-null mice with HP1 immunofluorescence and chromocenter/acrosome readouts\",\n      \"pmids\": [\"11861477\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How TBPL1 promotes chromocenter integrity mechanistically is unresolved\", \"Connection between heterochromatin role and transcriptional role not bridged\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Defined the central biochemical mechanism — a high-affinity, kinetically stable TBPL1-TFIIA complex — and showed this interaction governs TBPL1's cytoplasmic localization.\",\n      \"evidence\": \"Surface plasmon resonance kinetics, mutagenesis of TFIIA-binding residues, immunostaining and fractionation in NIH3T3 cells\",\n      \"pmids\": [\"14570910\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional purpose of cytoplasmic sequestration not fully explained\", \"Trigger that releases TBPL1 from TFIIA for nuclear entry not identified\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Showed TBPL1 acts as a p53-independent negative regulator of G2/M and a G2 DNA-damage checkpoint factor, coupling its regulated nuclear translocation to cell cycle control.\",\n      \"evidence\": \"TLP knockout in chicken DT40 cells, flow cytometry, UV/MMS stress challenge, and NLS-TLP overexpression\",\n      \"pmids\": [\"12773555\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Nuclear targets of TBPL1 during the checkpoint not identified\", \"Signal driving rapid stress-induced translocation unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrated the dual promoter logic of TBPL1 — activation of TATA-less and repression of TATA-containing promoters — and that TFIIA-binding determines which mode dominates.\",\n      \"evidence\": \"Reporter assays in TLP-null DT40 cells with rescue, TFIIA-binding mutants, and TATA-insertion mutagenesis at the TdT promoter\",\n      \"pmids\": [\"12682363\", \"11453637\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide promoter repertoire not mapped\", \"Whether activation requires additional co-factors beyond TFIIA unclear\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified specific natural target genes (NF1 activated, c-fos repressed) and confirmed in vivo relevance, contrasting TBPL1 and TBP as reciprocal regulators acting through TFIIA.\",\n      \"evidence\": \"EMSA with purified TLF-TFIIA, promoter reporter assays, NF1 mRNA quantification, and TLF-KO mouse analysis\",\n      \"pmids\": [\"15767669\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Breadth of TATA-less target genes in vivo not defined\", \"Sequence determinants of TBPL1 promoter recognition not resolved here\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Opened a cancer-relevant regulatory dimension by showing TBPL1 is post-transcriptionally repressed by a microRNA and supports tumor cell proliferation.\",\n      \"evidence\": \"miR-133b 3'-UTR luciferase reporter, mimic/inhibitor and siRNA experiments, and MTT proliferation assay in colorectal cancer cells\",\n      \"pmids\": [\"24870791\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream transcriptional program mediating proliferation not defined\", \"Single cancer-type context\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Reinforced microRNA control of TBPL1 with a second regulator and extended its phenotypic contribution to invasion and migration.\",\n      \"evidence\": \"miR-18a 3'-UTR luciferase reporter, RT-qPCR, Western blot, MTT, invasion and wound-healing assays in colorectal cancer cells\",\n      \"pmids\": [\"26398009\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link from TBPL1 to migration/invasion not established\", \"No in vivo confirmation\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed TBPL1 in a defined disease signaling axis (C-MYC -> miR-9-5p -| TBPL1) in pulmonary fibrosis, indicating its expression is tuned by upstream oncogenic transcription factors.\",\n      \"evidence\": \"ChIP for C-MYC, dual-luciferase reporter for miR-9-5p targeting TBPL1, siRNA/inhibitor studies, and bleomycin mouse model\",\n      \"pmids\": [\"35122989\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether TBPL1's transcriptional activity mediates the fibrotic phenotype not shown\", \"Direct TBPL1 target genes in fibroblasts unidentified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established a nucleolar function, showing TBPL1 binds TCT motifs at rDNA intergenic spacers to coordinate Pol II and Pol I activity for rRNA biogenesis.\",\n      \"evidence\": \"Compartment-enriched proximity biotinylation (compBioID), ChIP, RNA-seq, nucleolar fractionation, and depletion phenotyping\",\n      \"pmids\": [\"39505901\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which TBPL1 couples Pol II to Pol I at IGS not detailed\", \"Functional role of PAF1 association with TBPL1 not dissected\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected TBPL1 to breast cancer biology, showing knockout reshapes transcriptomes governing migration, proliferation and metastasis and that TBPL1 is overexpressed in tumor cells.\",\n      \"evidence\": \"CRISPR/Cas9 knockout, RNA-seq, and in vivo tumor assay across multiple breast cancer cell lines\",\n      \"pmids\": [\"41152284\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct promoter targets among the altered genes not identified\", \"Limited mechanistic depth beyond transcriptome-level association\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TBPL1's transcriptional/TFIIA-sequestering activity, its cell-cycle checkpoint role, its nucleolar rDNA function, and its heterochromatin/spermiogenesis requirement integrate into a unified mechanism remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No genome-wide map unifying TBPL1 binding sites across promoters, IGS, and heterochromatin\", \"Signal controlling regulated cytoplasm-to-nucleus translocation unknown\", \"Mechanistic basis of chromocenter integrity role uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [4, 6, 10]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [6, 10]},\n      {\"term_id\": \"GO:0140223\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [4, 6, 10]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"GTF2A1\", \"PAF1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}