{"gene":"TCEA2","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":1997,"finding":"TCEA2 encodes a transcription elongation factor (TFIIS family member) expressed primarily in the testis, with a distinct genomic structure of seven exons and six introns spanning ~7 kb, containing regulatory factor-binding sites in its 5' flanking region distinct from the ubiquitously expressed TFIIS gene.","method":"Genomic cloning, sequencing, and structural characterization of the TCEA2 gene","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genomic characterization with sequencing and structural analysis, single lab, establishes gene identity and testis-specific expression context","pmids":["9441762"],"is_preprint":false},{"year":2014,"finding":"TCEA2 physically interacts with BRCA1 (identified as a new BRCA1 protein-interacting partner), and genetic interactions between BRCA1 and TCEA2 were detected, implicating TCEA2 in BRCA1's function in the response to transcription-associated DNA damage.","method":"Systematic protein interaction screens (complementary systematic screens for BRCA1 interactors) followed by genetic interaction analysis","journal":"Genes & development","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — interaction identified by systematic screen with genetic interaction validation, single lab, two complementary methods","pmids":["25184681"],"is_preprint":false},{"year":2013,"finding":"TCEA2 is transcriptionally upregulated downstream of the nuclear receptor FXR in hepatocytes; FXR activation (by GW4064 agonist or cisplatin) trans-activates response elements in the TCEA2 promoter region, and this regulation occurs in both human hepatocytes and FXR/RXR-transfected hepatoma cells.","method":"Gene expression profiling of 109 chemoresistance genes following FXR activation, with FXR/RXR transfection and pharmacological activation by GW4064; FXR-mediated trans-activation of promoter response elements demonstrated","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — promoter trans-activation assay plus expression analysis in two cell models, single lab","pmids":["23680185"],"is_preprint":false},{"year":2025,"finding":"During co-directional transcription-replication conflicts (TRCs), the CUL3-KCTD10 E3 ubiquitin ligase complex ubiquitinates TCEA2, leading to its removal from the RNA polymerase II complex; this nonproteolytic ubiquitination transiently remodels the RNA polymerase II complex to permit replisome bypass. In the absence of KCTD10, TCEA2 is retained at the RNA polymerase complex, causing accumulation of TRCs and increased DNA damage.","method":"Co-IP/interaction studies demonstrating KCTD10 interaction with replisome and transcription machinery; ubiquitination assays; KCTD10 knockout cells showing increased TCEA2 retention, TRC accumulation, and DNA damage readouts","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (protein interaction, ubiquitination assay, KO phenotype with mechanistic readouts), peer-reviewed in Nature, corroborated by a separate review paper","pmids":["41062692"],"is_preprint":false},{"year":2026,"finding":"KCTD10-mediated ubiquitination of TCEA2 is nonproteolytic and functions to remodel RNA polymerase II at sites of co-directional transcription-replication conflicts, allowing replisome bypass without degrading TCEA2.","method":"Mechanistic review/synthesis of KCTD10-TCEA2 ubiquitination data; corroborates and clarifies findings from PMID:41062692","journal":"Trends in cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — review corroborating mechanism from a single primary study; no independent new experimental data presented in abstract","pmids":["42128708"],"is_preprint":false}],"current_model":"TCEA2 is a testis-enriched transcription elongation factor (TFIIS family) that associates with RNA polymerase II and is a substrate of the CUL3-KCTD10 E3 ubiquitin ligase, which nonproteolytically ubiquitinates TCEA2 at sites of co-directional transcription-replication conflicts to remodel the RNA polymerase II complex and permit replisome bypass, thereby maintaining genome stability; TCEA2 also interacts with BRCA1 in the response to transcription-associated DNA damage and is transcriptionally regulated by the nuclear receptor FXR."},"narrative":{"mechanistic_narrative":"TCEA2 is a testis-enriched transcription elongation factor of the TFIIS family that associates with the RNA polymerase II complex and contributes to maintaining genome stability during conflicts between transcription and replication [PMID:9441762, PMID:41062692]. At sites of co-directional transcription-replication conflicts, the CUL3-KCTD10 E3 ubiquitin ligase ubiquitinates TCEA2 in a nonproteolytic manner, removing it from RNA polymerase II to transiently remodel the polymerase complex and permit replisome bypass; loss of KCTD10 causes TCEA2 retention, accumulation of transcription-replication conflicts, and elevated DNA damage [PMID:41062692, PMID:42128708]. Consistent with this genome-protective role, TCEA2 physically and genetically interacts with BRCA1 in the response to transcription-associated DNA damage [PMID:25184681]. At the transcriptional level, TCEA2 is induced downstream of the nuclear receptor FXR, which trans-activates response elements in the TCEA2 promoter in hepatocytes [PMID:23680185]. Its testis-restricted expression pattern is distinct from the ubiquitously expressed TFIIS gene, indicating a specialized regulatory context [PMID:9441762].","teleology":[{"year":1997,"claim":"Established that TCEA2 is a distinct, testis-enriched member of the TFIIS transcription elongation factor family, separating it from the ubiquitous TFIIS gene and defining its tissue context.","evidence":"Genomic cloning, sequencing, and structural characterization of the TCEA2 gene","pmids":["9441762"],"confidence":"Medium","gaps":["No direct biochemical demonstration of elongation activity for the TCEA2 protein itself","Functional consequence of testis-restricted expression not defined","No interaction partners identified at this stage"]},{"year":2013,"claim":"Identified an upstream transcriptional regulator of TCEA2, showing it is induced by the nuclear receptor FXR through promoter response elements.","evidence":"Expression profiling and promoter trans-activation assays with FXR/RXR transfection and GW4064 activation in hepatocyte and hepatoma models","pmids":["23680185"],"confidence":"Medium","gaps":["Functional consequence of FXR-driven TCEA2 induction not established","Single-lab study in liver-derived cells only","Connection between FXR regulation and TCEA2's genome-stability role unexplored"]},{"year":2014,"claim":"Placed TCEA2 in the DNA damage response by identifying it as a BRCA1 physical and genetic interactor linked to transcription-associated damage.","evidence":"Systematic protein interaction screens for BRCA1 partners followed by genetic interaction analysis","pmids":["25184681"],"confidence":"Medium","gaps":["Direct, reciprocally validated binding interface not mapped","Mechanism of how TCEA2 contributes to BRCA1 function unresolved","Single-lab screen-based identification"]},{"year":2025,"claim":"Defined a mechanism by which TCEA2 is regulated at transcription-replication conflicts, showing CUL3-KCTD10 nonproteolytically ubiquitinates TCEA2 to remodel RNA polymerase II and permit replisome bypass.","evidence":"Co-IP/interaction studies, ubiquitination assays, and KCTD10 knockout cells with TRC and DNA damage readouts","pmids":["41062692"],"confidence":"High","gaps":["Ubiquitination site(s) on TCEA2 and how they trigger removal not detailed","Structural basis of RNA Pol II remodeling unresolved","Whether the BRCA1 and FXR axes intersect with the KCTD10 pathway untested"]},{"year":2026,"claim":"Clarified that the KCTD10-mediated modification is nonproteolytic and serves as a remodeling rather than a degradation signal for TCEA2.","evidence":"Mechanistic review synthesizing the KCTD10-TCEA2 ubiquitination data","pmids":["42128708"],"confidence":"Medium","gaps":["Review corroborating a single primary study; no new independent experimental data","Reader machinery interpreting the nonproteolytic ubiquitin mark not identified"]},{"year":null,"claim":"How TCEA2's testis-enriched expression, FXR transcriptional control, and BRCA1 interaction integrate with its KCTD10-regulated role at transcription-replication conflicts remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking the regulatory inputs (FXR), partners (BRCA1), and the KCTD10 ubiquitination mechanism","Physiological role in testis tissue uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[1,3]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,3]}],"complexes":["RNA polymerase II complex"],"partners":["BRCA1","KCTD10","CUL3","FXR"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15560","full_name":"Transcription elongation factor A protein 2","aliases":["Testis-specific S-II","Transcription elongation factor S-II protein 2","Transcription elongation factor TFIIS.l"],"length_aa":299,"mass_kda":33.6,"function":"Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q15560/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TCEA2","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TCEA2","total_profiled":1310},"omim":[{"mim_id":"604784","title":"TRANSCRIPTION ELONGATION FACTOR A, 2; TCEA2","url":"https://www.omim.org/entry/604784"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Centrosome","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TCEA2"},"hgnc":{"alias_symbol":["TFIIS"],"prev_symbol":[]},"alphafold":{"accession":"Q15560","domains":[{"cath_id":"1.20.930.10","chopping":"3-84","consensus_level":"high","plddt":84.312,"start":3,"end":84},{"cath_id":"-","chopping":"136-242","consensus_level":"high","plddt":90.2382,"start":136,"end":242},{"cath_id":"2.20.25.10","chopping":"253-297","consensus_level":"high","plddt":89.9471,"start":253,"end":297}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15560","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15560-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15560-F1-predicted_aligned_error_v6.png","plddt_mean":80.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TCEA2","jax_strain_url":"https://www.jax.org/strain/search?query=TCEA2"},"sequence":{"accession":"Q15560","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15560.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15560/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15560"}},"corpus_meta":[{"pmid":"18506748","id":"PMC_18506748","title":"Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression.","date":"2008","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/18506748","citation_count":281,"is_preprint":false},{"pmid":"25184681","id":"PMC_25184681","title":"Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage.","date":"2014","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/25184681","citation_count":86,"is_preprint":false},{"pmid":"38898508","id":"PMC_38898508","title":"Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.","date":"2024","source":"Genome medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38898508","citation_count":66,"is_preprint":false},{"pmid":"23680185","id":"PMC_23680185","title":"Activation of the nuclear receptor FXR enhances hepatocyte chemoprotection and liver tumor chemoresistance against genotoxic compounds.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/23680185","citation_count":50,"is_preprint":false},{"pmid":"9441762","id":"PMC_9441762","title":"Genomic characterization of a testis-specific TFIIS (TCEA2) gene.","date":"1997","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9441762","citation_count":18,"is_preprint":false},{"pmid":"35389552","id":"PMC_35389552","title":"Posttranslational modification of Aurora A-NSD2 loop contributes to drug resistance in t(4;14) multiple myeloma.","date":"2022","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35389552","citation_count":11,"is_preprint":false},{"pmid":"37270558","id":"PMC_37270558","title":"Investigation of enzalutamide, docetaxel, and cabazitaxel resistance in the castration resistant prostate cancer cell line C4 using genome-wide CRISPR/Cas9 screening.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37270558","citation_count":11,"is_preprint":false},{"pmid":"10689187","id":"PMC_10689187","title":"Gene structure and chromosome mapping of mouse transcription elongation factor S-II (Tcea1).","date":"2000","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/10689187","citation_count":8,"is_preprint":false},{"pmid":"39333727","id":"PMC_39333727","title":"Proteome-wide mendelian randomization identifies novel therapeutic targets for chronic kidney disease.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39333727","citation_count":6,"is_preprint":false},{"pmid":"41062692","id":"PMC_41062692","title":"KCTD10 is a sensor for co-directional transcription-replication conflicts.","date":"2025","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/41062692","citation_count":3,"is_preprint":false},{"pmid":"42128708","id":"PMC_42128708","title":"KCTD10 resolves co-directional transcription-replication conflicts.","date":"2026","source":"Trends in cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/42128708","citation_count":0,"is_preprint":false},{"pmid":"41163109","id":"PMC_41163109","title":"Epigenetic mediation may explain intergenerational associations between maternal obesogenic lifestyle and children's birth weight: findings from the NorthPop prospective birth cohort.","date":"2025","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/41163109","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8368,"output_tokens":1352,"usd":0.022692,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8002,"output_tokens":2107,"usd":0.046343,"stage2_stop_reason":"end_turn"},"total_usd":0.069035,"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\": 1997,\n      \"finding\": \"TCEA2 encodes a transcription elongation factor (TFIIS family member) expressed primarily in the testis, with a distinct genomic structure of seven exons and six introns spanning ~7 kb, containing regulatory factor-binding sites in its 5' flanking region distinct from the ubiquitously expressed TFIIS gene.\",\n      \"method\": \"Genomic cloning, sequencing, and structural characterization of the TCEA2 gene\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genomic characterization with sequencing and structural analysis, single lab, establishes gene identity and testis-specific expression context\",\n      \"pmids\": [\"9441762\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"TCEA2 physically interacts with BRCA1 (identified as a new BRCA1 protein-interacting partner), and genetic interactions between BRCA1 and TCEA2 were detected, implicating TCEA2 in BRCA1's function in the response to transcription-associated DNA damage.\",\n      \"method\": \"Systematic protein interaction screens (complementary systematic screens for BRCA1 interactors) followed by genetic interaction analysis\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — interaction identified by systematic screen with genetic interaction validation, single lab, two complementary methods\",\n      \"pmids\": [\"25184681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TCEA2 is transcriptionally upregulated downstream of the nuclear receptor FXR in hepatocytes; FXR activation (by GW4064 agonist or cisplatin) trans-activates response elements in the TCEA2 promoter region, and this regulation occurs in both human hepatocytes and FXR/RXR-transfected hepatoma cells.\",\n      \"method\": \"Gene expression profiling of 109 chemoresistance genes following FXR activation, with FXR/RXR transfection and pharmacological activation by GW4064; FXR-mediated trans-activation of promoter response elements demonstrated\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — promoter trans-activation assay plus expression analysis in two cell models, single lab\",\n      \"pmids\": [\"23680185\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"During co-directional transcription-replication conflicts (TRCs), the CUL3-KCTD10 E3 ubiquitin ligase complex ubiquitinates TCEA2, leading to its removal from the RNA polymerase II complex; this nonproteolytic ubiquitination transiently remodels the RNA polymerase II complex to permit replisome bypass. In the absence of KCTD10, TCEA2 is retained at the RNA polymerase complex, causing accumulation of TRCs and increased DNA damage.\",\n      \"method\": \"Co-IP/interaction studies demonstrating KCTD10 interaction with replisome and transcription machinery; ubiquitination assays; KCTD10 knockout cells showing increased TCEA2 retention, TRC accumulation, and DNA damage readouts\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (protein interaction, ubiquitination assay, KO phenotype with mechanistic readouts), peer-reviewed in Nature, corroborated by a separate review paper\",\n      \"pmids\": [\"41062692\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"KCTD10-mediated ubiquitination of TCEA2 is nonproteolytic and functions to remodel RNA polymerase II at sites of co-directional transcription-replication conflicts, allowing replisome bypass without degrading TCEA2.\",\n      \"method\": \"Mechanistic review/synthesis of KCTD10-TCEA2 ubiquitination data; corroborates and clarifies findings from PMID:41062692\",\n      \"journal\": \"Trends in cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — review corroborating mechanism from a single primary study; no independent new experimental data presented in abstract\",\n      \"pmids\": [\"42128708\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TCEA2 is a testis-enriched transcription elongation factor (TFIIS family) that associates with RNA polymerase II and is a substrate of the CUL3-KCTD10 E3 ubiquitin ligase, which nonproteolytically ubiquitinates TCEA2 at sites of co-directional transcription-replication conflicts to remodel the RNA polymerase II complex and permit replisome bypass, thereby maintaining genome stability; TCEA2 also interacts with BRCA1 in the response to transcription-associated DNA damage and is transcriptionally regulated by the nuclear receptor FXR.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TCEA2 is a testis-enriched transcription elongation factor of the TFIIS family that associates with the RNA polymerase II complex and contributes to maintaining genome stability during conflicts between transcription and replication [#0, #3]. At sites of co-directional transcription-replication conflicts, the CUL3-KCTD10 E3 ubiquitin ligase ubiquitinates TCEA2 in a nonproteolytic manner, removing it from RNA polymerase II to transiently remodel the polymerase complex and permit replisome bypass; loss of KCTD10 causes TCEA2 retention, accumulation of transcription-replication conflicts, and elevated DNA damage [#3, #4]. Consistent with this genome-protective role, TCEA2 physically and genetically interacts with BRCA1 in the response to transcription-associated DNA damage [#1]. At the transcriptional level, TCEA2 is induced downstream of the nuclear receptor FXR, which trans-activates response elements in the TCEA2 promoter in hepatocytes [#2]. Its testis-restricted expression pattern is distinct from the ubiquitously expressed TFIIS gene, indicating a specialized regulatory context [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Established that TCEA2 is a distinct, testis-enriched member of the TFIIS transcription elongation factor family, separating it from the ubiquitous TFIIS gene and defining its tissue context.\",\n      \"evidence\": \"Genomic cloning, sequencing, and structural characterization of the TCEA2 gene\",\n      \"pmids\": [\"9441762\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct biochemical demonstration of elongation activity for the TCEA2 protein itself\",\n        \"Functional consequence of testis-restricted expression not defined\",\n        \"No interaction partners identified at this stage\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified an upstream transcriptional regulator of TCEA2, showing it is induced by the nuclear receptor FXR through promoter response elements.\",\n      \"evidence\": \"Expression profiling and promoter trans-activation assays with FXR/RXR transfection and GW4064 activation in hepatocyte and hepatoma models\",\n      \"pmids\": [\"23680185\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of FXR-driven TCEA2 induction not established\",\n        \"Single-lab study in liver-derived cells only\",\n        \"Connection between FXR regulation and TCEA2's genome-stability role unexplored\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Placed TCEA2 in the DNA damage response by identifying it as a BRCA1 physical and genetic interactor linked to transcription-associated damage.\",\n      \"evidence\": \"Systematic protein interaction screens for BRCA1 partners followed by genetic interaction analysis\",\n      \"pmids\": [\"25184681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct, reciprocally validated binding interface not mapped\",\n        \"Mechanism of how TCEA2 contributes to BRCA1 function unresolved\",\n        \"Single-lab screen-based identification\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a mechanism by which TCEA2 is regulated at transcription-replication conflicts, showing CUL3-KCTD10 nonproteolytically ubiquitinates TCEA2 to remodel RNA polymerase II and permit replisome bypass.\",\n      \"evidence\": \"Co-IP/interaction studies, ubiquitination assays, and KCTD10 knockout cells with TRC and DNA damage readouts\",\n      \"pmids\": [\"41062692\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Ubiquitination site(s) on TCEA2 and how they trigger removal not detailed\",\n        \"Structural basis of RNA Pol II remodeling unresolved\",\n        \"Whether the BRCA1 and FXR axes intersect with the KCTD10 pathway untested\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Clarified that the KCTD10-mediated modification is nonproteolytic and serves as a remodeling rather than a degradation signal for TCEA2.\",\n      \"evidence\": \"Mechanistic review synthesizing the KCTD10-TCEA2 ubiquitination data\",\n      \"pmids\": [\"42128708\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Review corroborating a single primary study; no new independent experimental data\",\n        \"Reader machinery interpreting the nonproteolytic ubiquitin mark not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TCEA2's testis-enriched expression, FXR transcriptional control, and BRCA1 interaction integrate with its KCTD10-regulated role at transcription-replication conflicts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No unified model linking the regulatory inputs (FXR), partners (BRCA1), and the KCTD10 ubiquitination mechanism\",\n        \"Physiological role in testis tissue uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\"RNA polymerase II complex\"],\n    \"partners\": [\"BRCA1\", \"KCTD10\", \"CUL3\", \"FXR\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}