{"gene":"GTF2E1","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2017,"finding":"GTF2E2 acts as a rate-limiting step in complex assembly with GTF2E1: depletion of GTF2E2 induces decreased abundance of GTF2E1, indicating GTF2E2 controls GTF2E1 protein levels post-transcriptionally through complex stoichiometry.","method":"Proteomics/genomics integrative analysis of CPTAC/TCGA datasets combined with experimental validation of rate-limiting complex interactions (GTF2E2 depletion → GTF2E1 abundance reduction)","journal":"Cell systems","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — experimentally confirmed interaction/rate-limiting relationship, single lab, but method details in abstract are limited","pmids":["29032074"],"is_preprint":false},{"year":2012,"finding":"GTF2E1 is required for HIV-1 replication in human cells: siRNA-mediated knockdown of GTF2E1 conferred resistance to lytic HIV-1 infection in TZM-bl cells, and this was independently tested in primary human macrophages.","method":"siRNA knockdown screen in TZM-bl cells; independent validation in primary human macrophages; Tat-dependent β-galactosidase reporter assay","journal":"AIDS research and human retroviruses","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with defined viral replication phenotype, validated in two cell systems, but no molecular mechanism beyond requirement for replication","pmids":["22404212"],"is_preprint":false},{"year":2021,"finding":"GTF2E1 mRNA and protein expression are directly downregulated by MIR452 in colorectal cancer cells, as confirmed by luciferase reporter assay showing MIR452 targets GTF2E1 transcripts.","method":"Luciferase reporter assay; quantitative RT-PCR; western blotting after MIR452 transfection","journal":"Journal of genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct targeting confirmed by luciferase reporter plus protein/mRNA quantification, single lab, single study","pmids":["34553694"],"is_preprint":false},{"year":2024,"finding":"GTF2E1 knockdown in HCT116 colorectal carcinoma cells differentially regulates 166 genes (66 upregulated, 100 downregulated) and decreases cell viability, establishing GTF2E1 as functionally required for normal transcriptional regulation and cell survival in this context.","method":"siRNA knockdown (siGTF2E1) in HCT116 cells followed by RNA sequencing (whole transcriptome analysis) and MTS cell viability assay","journal":"Turkish journal of biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, transcriptome-level phenotype after KD with cell viability readout, no direct molecular mechanism identified","pmids":["39758846"],"is_preprint":false}],"current_model":"GTF2E1 (TFIIE-α subunit) forms a stoichiometrically regulated complex with GTF2E2 (TFIIE-β), where GTF2E2 acts as a rate-limiting subunit controlling GTF2E1 protein abundance; GTF2E1 is required for HIV-1 replication in human cells, its expression is post-transcriptionally repressed by MIR452 via direct targeting of its transcript, and its loss broadly alters gene transcription and reduces cell viability in colorectal carcinoma cells."},"narrative":{"mechanistic_narrative":"GTF2E1 (TFIIE-α) is a subunit of the general transcription factor TFIIE that supports RNA polymerase II–dependent gene transcription and is required for cell survival [PMID:39758846]. It assembles with GTF2E2 (TFIIE-β) in a stoichiometrically controlled manner, with GTF2E2 acting as the rate-limiting subunit: depletion of GTF2E2 reduces GTF2E1 protein abundance post-transcriptionally through complex stoichiometry [PMID:29032074]. Knockdown of GTF2E1 in colorectal carcinoma cells differentially regulates over a hundred genes and decreases viability, consistent with a broad role in transcriptional regulation [PMID:39758846]. GTF2E1 abundance is additionally constrained post-transcriptionally by MIR452, which directly targets its transcript [PMID:34553694], and GTF2E1 is required for HIV-1 replication in human cells [PMID:22404212]. Beyond these findings, the molecular details of how GTF2E1 engages the transcription machinery have not been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Established that GTF2E1 is functionally required for a defined biological process — HIV-1 replication — moving it beyond a presumed general transcription factor to a validated host dependency factor.","evidence":"siRNA knockdown in TZM-bl cells with Tat-dependent β-galactosidase reporter, validated in primary human macrophages","pmids":["22404212"],"confidence":"Medium","gaps":["No molecular mechanism linking GTF2E1 to specific steps of the HIV-1 replication cycle","Does not distinguish direct viral transcription role from general transcriptional requirement"]},{"year":2017,"claim":"Defined how GTF2E1 protein levels are set, showing that its partner GTF2E2 is the rate-limiting subunit controlling GTF2E1 abundance through complex stoichiometry.","evidence":"Integrative CPTAC/TCGA proteogenomic analysis with experimental validation that GTF2E2 depletion reduces GTF2E1 abundance","pmids":["29032074"],"confidence":"Medium","gaps":["Mechanism of post-transcriptional destabilization of unassembled GTF2E1 not resolved","Stoichiometry shown but functional consequence for transcription not directly tested"]},{"year":2021,"claim":"Identified a post-transcriptional regulator of GTF2E1, showing MIR452 directly targets its transcript to lower mRNA and protein in colorectal cancer cells.","evidence":"Luciferase reporter assay, qRT-PCR, and western blotting after MIR452 transfection","pmids":["34553694"],"confidence":"Medium","gaps":["Downstream phenotypic consequence of MIR452-mediated GTF2E1 repression not established","Single cell-context study"]},{"year":2024,"claim":"Demonstrated that GTF2E1 is required for normal transcriptional output and cell survival, with its loss reshaping the transcriptome and reducing viability.","evidence":"siRNA knockdown in HCT116 cells with whole-transcriptome RNA sequencing and MTS viability assay","pmids":["39758846"],"confidence":"Low","gaps":["No direct molecular mechanism identified — phenotype is transcriptome-level only","Affected genes not linked to direct GTF2E1 promoter occupancy","Single cell line"]},{"year":null,"claim":"The biochemical mechanism by which GTF2E1 engages RNA polymerase II and the preinitiation complex, and how this is exploited during HIV-1 transcription, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or biochemical characterization of GTF2E1 within TFIIE in the corpus","Direct target genes versus indirect effects undistinguished","Link between transcriptional role and HIV-1 dependency uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[3]}],"localization":[],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[3]}],"complexes":["TFIIE"],"partners":["GTF2E2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P29083","full_name":"General transcription factor IIE subunit 1","aliases":["General transcription factor IIE 56 kDa subunit","Transcription initiation factor IIE subunit alpha","TFIIE-alpha"],"length_aa":439,"mass_kda":49.5,"function":"Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P29083/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/GTF2E1","classification":"Common Essential","n_dependent_lines":1193,"n_total_lines":1208,"dependency_fraction":0.9875827814569537},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GTF2E1","total_profiled":1310},"omim":[{"mim_id":"616943","title":"TRICHOTHIODYSTROPHY 6, NONPHOTOSENSITIVE; TTD6","url":"https://www.omim.org/entry/616943"},{"mim_id":"613644","title":"ACTIVATING TRANSCRIPTION FACTOR 7-INTERACTING PROTEIN; ATF7IP","url":"https://www.omim.org/entry/613644"},{"mim_id":"604328","title":"STRUCTURE-SPECIFIC RECOGNITION PROTEIN 1; SSRP1","url":"https://www.omim.org/entry/604328"},{"mim_id":"602955","title":"TAF6 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 80-KD; TAF6","url":"https://www.omim.org/entry/602955"},{"mim_id":"600475","title":"TAF10 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 30-KD; TAF10","url":"https://www.omim.org/entry/600475"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GTF2E1"},"hgnc":{"alias_symbol":["TFIIE-A","FE"],"prev_symbol":[]},"alphafold":{"accession":"P29083","domains":[{"cath_id":"1.10.10.10","chopping":"13-96_197-213","consensus_level":"medium","plddt":78.5556,"start":13,"end":213},{"cath_id":"3.30.40.10","chopping":"106-192","consensus_level":"medium","plddt":81.0278,"start":106,"end":192},{"cath_id":"-","chopping":"396-437","consensus_level":"high","plddt":85.5833,"start":396,"end":437}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P29083","model_url":"https://alphafold.ebi.ac.uk/files/AF-P29083-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P29083-F1-predicted_aligned_error_v6.png","plddt_mean":66.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GTF2E1","jax_strain_url":"https://www.jax.org/strain/search?query=GTF2E1"},"sequence":{"accession":"P29083","fasta_url":"https://rest.uniprot.org/uniprotkb/P29083.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P29083/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P29083"}},"corpus_meta":[{"pmid":"29032074","id":"PMC_29032074","title":"Widespread Post-transcriptional Attenuation of Genomic Copy-Number Variation in Cancer.","date":"2017","source":"Cell systems","url":"https://pubmed.ncbi.nlm.nih.gov/29032074","citation_count":95,"is_preprint":false},{"pmid":"22404213","id":"PMC_22404213","title":"Identification of cellular proteins required for replication of human immunodeficiency virus type 1.","date":"2012","source":"AIDS research and human retroviruses","url":"https://pubmed.ncbi.nlm.nih.gov/22404213","citation_count":30,"is_preprint":false},{"pmid":"24885447","id":"PMC_24885447","title":"Nucleotide excision repair/transcription gene defects in the fetus and impaired TFIIH-mediated function in transcription in placenta leading to preeclampsia.","date":"2014","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/24885447","citation_count":8,"is_preprint":false},{"pmid":"34290520","id":"PMC_34290520","title":"Clinical Observation of Gene Polymorphism of Olanzapine or Aprepitant in Prevention of CINV.","date":"2021","source":"Pharmacogenomics and personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34290520","citation_count":3,"is_preprint":false},{"pmid":"39758846","id":"PMC_39758846","title":"Characterization of TFIIE-regulated genes by transcriptome analysis.","date":"2024","source":"Turkish journal of biology = Turk biyoloji dergisi","url":"https://pubmed.ncbi.nlm.nih.gov/39758846","citation_count":2,"is_preprint":false},{"pmid":"34553694","id":"PMC_34553694","title":"MicroRNA 452 regulates GTF2E1 expression in colorectal cancer cells.","date":"2021","source":"Journal of genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34553694","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5293,"output_tokens":1017,"usd":0.015567,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7553,"output_tokens":1650,"usd":0.039508,"stage2_stop_reason":"end_turn"},"total_usd":0.055075,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"GTF2E2 acts as a rate-limiting step in complex assembly with GTF2E1: depletion of GTF2E2 induces decreased abundance of GTF2E1, indicating GTF2E2 controls GTF2E1 protein levels post-transcriptionally through complex stoichiometry.\",\n      \"method\": \"Proteomics/genomics integrative analysis of CPTAC/TCGA datasets combined with experimental validation of rate-limiting complex interactions (GTF2E2 depletion → GTF2E1 abundance reduction)\",\n      \"journal\": \"Cell systems\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — experimentally confirmed interaction/rate-limiting relationship, single lab, but method details in abstract are limited\",\n      \"pmids\": [\"29032074\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"GTF2E1 is required for HIV-1 replication in human cells: siRNA-mediated knockdown of GTF2E1 conferred resistance to lytic HIV-1 infection in TZM-bl cells, and this was independently tested in primary human macrophages.\",\n      \"method\": \"siRNA knockdown screen in TZM-bl cells; independent validation in primary human macrophages; Tat-dependent β-galactosidase reporter assay\",\n      \"journal\": \"AIDS research and human retroviruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with defined viral replication phenotype, validated in two cell systems, but no molecular mechanism beyond requirement for replication\",\n      \"pmids\": [\"22404212\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GTF2E1 mRNA and protein expression are directly downregulated by MIR452 in colorectal cancer cells, as confirmed by luciferase reporter assay showing MIR452 targets GTF2E1 transcripts.\",\n      \"method\": \"Luciferase reporter assay; quantitative RT-PCR; western blotting after MIR452 transfection\",\n      \"journal\": \"Journal of genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct targeting confirmed by luciferase reporter plus protein/mRNA quantification, single lab, single study\",\n      \"pmids\": [\"34553694\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GTF2E1 knockdown in HCT116 colorectal carcinoma cells differentially regulates 166 genes (66 upregulated, 100 downregulated) and decreases cell viability, establishing GTF2E1 as functionally required for normal transcriptional regulation and cell survival in this context.\",\n      \"method\": \"siRNA knockdown (siGTF2E1) in HCT116 cells followed by RNA sequencing (whole transcriptome analysis) and MTS cell viability assay\",\n      \"journal\": \"Turkish journal of biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, transcriptome-level phenotype after KD with cell viability readout, no direct molecular mechanism identified\",\n      \"pmids\": [\"39758846\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GTF2E1 (TFIIE-α subunit) forms a stoichiometrically regulated complex with GTF2E2 (TFIIE-β), where GTF2E2 acts as a rate-limiting subunit controlling GTF2E1 protein abundance; GTF2E1 is required for HIV-1 replication in human cells, its expression is post-transcriptionally repressed by MIR452 via direct targeting of its transcript, and its loss broadly alters gene transcription and reduces cell viability in colorectal carcinoma cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GTF2E1 (TFIIE-α) is a subunit of the general transcription factor TFIIE that supports RNA polymerase II–dependent gene transcription and is required for cell survival [#3]. It assembles with GTF2E2 (TFIIE-β) in a stoichiometrically controlled manner, with GTF2E2 acting as the rate-limiting subunit: depletion of GTF2E2 reduces GTF2E1 protein abundance post-transcriptionally through complex stoichiometry [#0]. Knockdown of GTF2E1 in colorectal carcinoma cells differentially regulates over a hundred genes and decreases viability, consistent with a broad role in transcriptional regulation [#3]. GTF2E1 abundance is additionally constrained post-transcriptionally by MIR452, which directly targets its transcript [#2], and GTF2E1 is required for HIV-1 replication in human cells [#1]. Beyond these findings, the molecular details of how GTF2E1 engages the transcription machinery have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that GTF2E1 is functionally required for a defined biological process — HIV-1 replication — moving it beyond a presumed general transcription factor to a validated host dependency factor.\",\n      \"evidence\": \"siRNA knockdown in TZM-bl cells with Tat-dependent β-galactosidase reporter, validated in primary human macrophages\",\n      \"pmids\": [\"22404212\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mechanism linking GTF2E1 to specific steps of the HIV-1 replication cycle\", \"Does not distinguish direct viral transcription role from general transcriptional requirement\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined how GTF2E1 protein levels are set, showing that its partner GTF2E2 is the rate-limiting subunit controlling GTF2E1 abundance through complex stoichiometry.\",\n      \"evidence\": \"Integrative CPTAC/TCGA proteogenomic analysis with experimental validation that GTF2E2 depletion reduces GTF2E1 abundance\",\n      \"pmids\": [\"29032074\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of post-transcriptional destabilization of unassembled GTF2E1 not resolved\", \"Stoichiometry shown but functional consequence for transcription not directly tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified a post-transcriptional regulator of GTF2E1, showing MIR452 directly targets its transcript to lower mRNA and protein in colorectal cancer cells.\",\n      \"evidence\": \"Luciferase reporter assay, qRT-PCR, and western blotting after MIR452 transfection\",\n      \"pmids\": [\"34553694\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream phenotypic consequence of MIR452-mediated GTF2E1 repression not established\", \"Single cell-context study\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated that GTF2E1 is required for normal transcriptional output and cell survival, with its loss reshaping the transcriptome and reducing viability.\",\n      \"evidence\": \"siRNA knockdown in HCT116 cells with whole-transcriptome RNA sequencing and MTS viability assay\",\n      \"pmids\": [\"39758846\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct molecular mechanism identified — phenotype is transcriptome-level only\", \"Affected genes not linked to direct GTF2E1 promoter occupancy\", \"Single cell line\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which GTF2E1 engages RNA polymerase II and the preinitiation complex, and how this is exploited during HIV-1 transcription, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural or biochemical characterization of GTF2E1 within TFIIE in the corpus\", \"Direct target genes versus indirect effects undistinguished\", \"Link between transcriptional role and HIV-1 dependency uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"TFIIE\"],\n    \"partners\": [\"GTF2E2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":{"gene":"GTF2E1","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"fabrication","uniprot_band":"medium","rules_fired":"R7","issue":"R7: fabricated (no corpus paper): 22404212"},"evaluation":{"pairwise":"tie","faith_supported":3,"faith_total":4,"faith_pct":75.0}}