{"gene":"GTF2H1","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2018,"finding":"GTF2H1 (p62) is a core subunit of the TFIIH complex whose expression is transcriptionally promoted by the SWI/SNF ATPases BRM/SMARCA2 and BRG1/SMARCA4; inactivation of either ATPase downregulates GTF2H1, compromising TFIIH stability and function in both transcription and nucleotide excision repair (NER). The sensitivity of SWI/SNF-deficient cells to UV irradiation and cisplatin depends directly on GTF2H1 levels.","method":"RNAi/genetic depletion of BRM or BRG1, measurement of GTF2H1 expression and TFIIH stability, UV and cisplatin sensitivity assays in SWI/SNF-deficient cancer cells","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal functional epistasis established by depletion experiments with defined cellular phenotypes (NER, transcription, drug sensitivity); multiple orthogonal methods in a focused mechanistic study","pmids":["30287812"],"is_preprint":false},{"year":2019,"finding":"MITF directly transactivates GTF2H1 as a core element of TFIIH, thereby controlling general transcription and UV-induced nucleotide excision repair in the melanocytic lineage. MITF depletion leads to consecutive loss of CDK7 in the TFIIH-CAK subcomplex, targeted for proteasomal degradation, establishing a MITF→GTF2H1→TFIIH-CAK regulatory axis.","method":"Chromatin immunoprecipitation, transactivation assays, MITF depletion (siRNA/shRNA) with measurement of GTF2H1 levels, CDK7 protein stability, NER activity, and transcriptional output in melanoma cells and in vivo models","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct transactivation demonstrated by ChIP and reporter assays; functional consequences (NER, CDK7 stability, transcription) confirmed by loss-of-function with multiple readouts in single focused study","pmids":["30651597"],"is_preprint":false},{"year":2010,"finding":"GTF2H1 protein level is upregulated in human hepatoma HepG2 cells treated with zidovudine (AZT), and knockdown of XPC (a NER recognition factor that acts upstream of TFIIH/GTF2H1) increases AZT incorporation into DNA and sensitizes cells to AZT toxicity, placing GTF2H1-containing TFIIH in the NER pathway responding to AZT-induced DNA damage.","method":"Real-time PCR array, Western blot for GTF2H1 protein, shRNA knockdown of XPC, cell viability, LDH release, apoptosis, and cell cycle assays in HepG2 cells","journal":"Toxicology and Applied Pharmacology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — GTF2H1 protein upregulation confirmed by Western blot; pathway placement inferred from XPC epistasis experiment; two orthogonal methods but GTF2H1-specific functional perturbation not performed","pmids":["21192964"],"is_preprint":false},{"year":2013,"finding":"GTF2H1 protein level is significantly increased in a dose-dependent manner in immortalized human hepatic THLE2 cells treated with AZT, implicating the NER pathway (of which TFIIH/GTF2H1 is a component) in the response to AZT-induced DNA damage in non-cancerous liver cells.","method":"PCR array expression profiling and Western blot for GTF2H1 protein across AZT dose range in THLE2 cells","journal":"International Journal of Biomedical Science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single method (Western blot) for GTF2H1 protein change; no GTF2H1-specific perturbation; corroborates prior finding but adds limited new mechanism","pmids":["23675285"],"is_preprint":false},{"year":1995,"finding":"GTF2H1 encodes the 62-kDa subunit of TFIIH and was precisely localized to the distal p13–proximal p15.1 region of human chromosome 11 by physical mapping using YACs, cosmids, and fluorescence in situ hybridization.","method":"Fluorescence in situ hybridization (FISH) on high-resolution banded chromosomes, YAC/cosmid physical mapping","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cytogenetic localization by FISH with physical map confirmation; foundational identity/localization result replicated across mapping approaches in one study","pmids":["7789978"],"is_preprint":false}],"current_model":"GTF2H1 encodes the p62/62-kDa core subunit of the transcription factor IIH (TFIIH) complex and is essential for both RNA polymerase II-dependent transcription and nucleotide excision repair (NER); its expression is directly transactivated by lineage-specific factors including MITF (in melanocytes) and maintained by the SWI/SNF ATPases BRM/BRG1, with loss of GTF2H1 destabilizing the entire TFIIH complex (including the CDK7-containing CAK subcomplex) and sensitizing cells to UV- and platinum-induced DNA damage."},"narrative":{"mechanistic_narrative":"GTF2H1 encodes the 62-kDa core subunit of the transcription factor IIH (TFIIH) complex, which functions in both RNA polymerase II-dependent transcription and nucleotide excision repair (NER) [PMID:30287812, PMID:7789978]. GTF2H1 levels set TFIIH stability and function: depletion of the SWI/SNF ATPases BRM/SMARCA2 or BRG1/SMARCA4 downregulates GTF2H1, compromising TFIIH integrity and rendering SWI/SNF-deficient cells sensitive to UV irradiation and cisplatin in a GTF2H1-dependent manner [PMID:30287812]. In the melanocytic lineage, MITF directly transactivates GTF2H1, and MITF loss collapses GTF2H1-dependent TFIIH with consequent proteasomal degradation of the CDK7-containing CAK subcomplex, defining a MITF→GTF2H1→TFIIH-CAK axis that governs general transcription and UV-induced NER [PMID:30651597]. Consistent with its NER role, GTF2H1 protein is induced in hepatic cells responding to AZT-induced DNA damage downstream of the recognition factor XPC [PMID:21192964].","teleology":[{"year":1995,"claim":"Establishing the molecular identity and genomic position of the gene was the first step, fixing GTF2H1 as the 62-kDa TFIIH subunit and assigning it a chromosomal locus.","evidence":"FISH on banded chromosomes with YAC/cosmid physical mapping","pmids":["7789978"],"confidence":"Medium","gaps":["No functional perturbation linking the locus to TFIIH activity","Provides identity/position but not mechanism in transcription or repair"]},{"year":2010,"claim":"Whether GTF2H1-containing TFIIH participates in the cellular response to a specific DNA-damaging agent was addressed by showing GTF2H1 induction and XPC-dependent NER engagement upon AZT treatment.","evidence":"PCR array, Western blot, and shRNA knockdown of XPC with viability/apoptosis assays in HepG2 hepatoma cells","pmids":["21192964"],"confidence":"Medium","gaps":["Pathway placement inferred from XPC epistasis; no GTF2H1-specific perturbation performed","Does not establish whether GTF2H1 induction is functionally required for AZT resistance"]},{"year":2013,"claim":"Whether GTF2H1 induction by AZT extends beyond cancer cells was tested by measuring dose-dependent upregulation in non-transformed hepatic cells.","evidence":"PCR array and Western blot across AZT dose range in immortalized THLE2 cells","pmids":["23675285"],"confidence":"Low","gaps":["Single-method protein measurement with no GTF2H1-specific functional perturbation","Corroborative only; adds little new mechanism beyond the prior HepG2 finding"]},{"year":2018,"claim":"The question of what maintains GTF2H1 expression and how its level controls TFIIH function was answered by showing SWI/SNF ATPases promote GTF2H1 transcription and that GTF2H1 abundance dictates TFIIH stability and DNA-damage sensitivity.","evidence":"RNAi depletion of BRM/BRG1, TFIIH stability and GTF2H1 expression measurement, UV and cisplatin sensitivity assays in SWI/SNF-deficient cancer cells","pmids":["30287812"],"confidence":"High","gaps":["Direct versus indirect transcriptional control of GTF2H1 by SWI/SNF not fully resolved","Whether the same dependency holds across non-cancer cell types untested"]},{"year":2019,"claim":"Lineage-specific control of GTF2H1 was established by demonstrating MITF directly transactivates it, defining a regulatory axis in which GTF2H1 loss destabilizes the TFIIH-CAK subcomplex.","evidence":"ChIP, transactivation/reporter assays, and MITF depletion with CDK7 stability, NER, and transcription readouts in melanoma cells and in vivo","pmids":["30651597"],"confidence":"High","gaps":["Generality of MITF control beyond the melanocytic lineage unknown","Mechanism of CDK7 degradation upon GTF2H1 loss not structurally defined"]},{"year":null,"claim":"The structural basis by which GTF2H1/p62 organizes TFIIH and coordinates the transcription versus NER functions of the complex remains uncharacterized in this corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or biochemical reconstitution of p62 within TFIIH in the timeline","Direct enzymatic or scaffolding contribution of GTF2H1 to NER not dissected"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140223","term_label":"general transcription initiation factor activity","supporting_discovery_ids":[0,1,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[0,1,2]}],"complexes":["TFIIH","TFIIH-CAK"],"partners":["CDK7","MITF","SMARCA2","SMARCA4","XPC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P32780","full_name":"General transcription factor IIH subunit 1","aliases":["Basic transcription factor 2 62 kDa subunit","BTF2 p62","General transcription factor IIH polypeptide 1","TFIIH basal transcription factor complex p62 subunit"],"length_aa":548,"mass_kda":62.0,"function":"Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P32780/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/GTF2H1","classification":"Common Essential","n_dependent_lines":1046,"n_total_lines":1208,"dependency_fraction":0.8658940397350994},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CDC7","stoichiometry":10.0},{"gene":"CDK7","stoichiometry":10.0},{"gene":"CETN2","stoichiometry":0.2},{"gene":"SSRP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/GTF2H1","total_profiled":1310},"omim":[{"mim_id":"619818","title":"ELONGATION FACTOR 1; ELOF1","url":"https://www.omim.org/entry/619818"},{"mim_id":"610651","title":"XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP B; XPB","url":"https://www.omim.org/entry/610651"},{"mim_id":"600475","title":"TAF10 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 30-KD; TAF10","url":"https://www.omim.org/entry/600475"},{"mim_id":"189972","title":"GENERAL TRANSCRIPTION FACTOR IIH, POLYPEPTIDE 1; GTF2H1","url":"https://www.omim.org/entry/189972"},{"mim_id":"154365","title":"PROTEASOME 26S SUBUNIT, ATPase, 2; PSMC2","url":"https://www.omim.org/entry/154365"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GTF2H1"},"hgnc":{"alias_symbol":["BTF2","P62","TFIIH"],"prev_symbol":[]},"alphafold":{"accession":"P32780","domains":[{"cath_id":"2.30.29.30","chopping":"7-107","consensus_level":"high","plddt":81.2693,"start":7,"end":107},{"cath_id":"-","chopping":"176-269_295-317","consensus_level":"high","plddt":73.6808,"start":176,"end":317},{"cath_id":"1.20.58","chopping":"454-546","consensus_level":"high","plddt":84.096,"start":454,"end":546}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P32780","model_url":"https://alphafold.ebi.ac.uk/files/AF-P32780-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P32780-F1-predicted_aligned_error_v6.png","plddt_mean":73.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GTF2H1","jax_strain_url":"https://www.jax.org/strain/search?query=GTF2H1"},"sequence":{"accession":"P32780","fasta_url":"https://rest.uniprot.org/uniprotkb/P32780.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P32780/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P32780"}},"corpus_meta":[{"pmid":"17129579","id":"PMC_17129579","title":"Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling.","date":"2006","source":"Chemico-biological interactions","url":"https://pubmed.ncbi.nlm.nih.gov/17129579","citation_count":140,"is_preprint":false},{"pmid":"7789978","id":"PMC_7789978","title":"A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.","date":"1995","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/7789978","citation_count":56,"is_preprint":false},{"pmid":"22581836","id":"PMC_22581836","title":"Polymorphisms in miRNA-binding sites of nucleotide excision repair genes and colorectal cancer risk.","date":"2012","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/22581836","citation_count":52,"is_preprint":false},{"pmid":"21251114","id":"PMC_21251114","title":"Integrated genomic profiling identifies loss of chromosome 11p impacting transcriptomic activity in aggressive pituitary PRL tumors.","date":"2011","source":"Brain pathology (Zurich, 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1p31 with major impact on acute-phase serum amyloid A.","date":"2010","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21124955","citation_count":21,"is_preprint":false},{"pmid":"24307700","id":"PMC_24307700","title":"HEFT: eQTL analysis of many thousands of expressed genes while simultaneously controlling for hidden factors.","date":"2013","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/24307700","citation_count":18,"is_preprint":false},{"pmid":"30651597","id":"PMC_30651597","title":"Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair.","date":"2019","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/30651597","citation_count":17,"is_preprint":false},{"pmid":"24589211","id":"PMC_24589211","title":"MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells.","date":"2014","source":"Chinese journal of 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The sensitivity of SWI/SNF-deficient cells to UV irradiation and cisplatin depends directly on GTF2H1 levels.\",\n      \"method\": \"RNAi/genetic depletion of BRM or BRG1, measurement of GTF2H1 expression and TFIIH stability, UV and cisplatin sensitivity assays in SWI/SNF-deficient cancer cells\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal functional epistasis established by depletion experiments with defined cellular phenotypes (NER, transcription, drug sensitivity); multiple orthogonal methods in a focused mechanistic study\",\n      \"pmids\": [\"30287812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MITF directly transactivates GTF2H1 as a core element of TFIIH, thereby controlling general transcription and UV-induced nucleotide excision repair in the melanocytic lineage. MITF depletion leads to consecutive loss of CDK7 in the TFIIH-CAK subcomplex, targeted for proteasomal degradation, establishing a MITF→GTF2H1→TFIIH-CAK regulatory axis.\",\n      \"method\": \"Chromatin immunoprecipitation, transactivation assays, MITF depletion (siRNA/shRNA) with measurement of GTF2H1 levels, CDK7 protein stability, NER activity, and transcriptional output in melanoma cells and in vivo models\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct transactivation demonstrated by ChIP and reporter assays; functional consequences (NER, CDK7 stability, transcription) confirmed by loss-of-function with multiple readouts in single focused study\",\n      \"pmids\": [\"30651597\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"GTF2H1 protein level is upregulated in human hepatoma HepG2 cells treated with zidovudine (AZT), and knockdown of XPC (a NER recognition factor that acts upstream of TFIIH/GTF2H1) increases AZT incorporation into DNA and sensitizes cells to AZT toxicity, placing GTF2H1-containing TFIIH in the NER pathway responding to AZT-induced DNA damage.\",\n      \"method\": \"Real-time PCR array, Western blot for GTF2H1 protein, shRNA knockdown of XPC, cell viability, LDH release, apoptosis, and cell cycle assays in HepG2 cells\",\n      \"journal\": \"Toxicology and Applied Pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — GTF2H1 protein upregulation confirmed by Western blot; pathway placement inferred from XPC epistasis experiment; two orthogonal methods but GTF2H1-specific functional perturbation not performed\",\n      \"pmids\": [\"21192964\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"GTF2H1 protein level is significantly increased in a dose-dependent manner in immortalized human hepatic THLE2 cells treated with AZT, implicating the NER pathway (of which TFIIH/GTF2H1 is a component) in the response to AZT-induced DNA damage in non-cancerous liver cells.\",\n      \"method\": \"PCR array expression profiling and Western blot for GTF2H1 protein across AZT dose range in THLE2 cells\",\n      \"journal\": \"International Journal of Biomedical Science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single method (Western blot) for GTF2H1 protein change; no GTF2H1-specific perturbation; corroborates prior finding but adds limited new mechanism\",\n      \"pmids\": [\"23675285\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"GTF2H1 encodes the 62-kDa subunit of TFIIH and was precisely localized to the distal p13–proximal p15.1 region of human chromosome 11 by physical mapping using YACs, cosmids, and fluorescence in situ hybridization.\",\n      \"method\": \"Fluorescence in situ hybridization (FISH) on high-resolution banded chromosomes, YAC/cosmid physical mapping\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cytogenetic localization by FISH with physical map confirmation; foundational identity/localization result replicated across mapping approaches in one study\",\n      \"pmids\": [\"7789978\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GTF2H1 encodes the p62/62-kDa core subunit of the transcription factor IIH (TFIIH) complex and is essential for both RNA polymerase II-dependent transcription and nucleotide excision repair (NER); its expression is directly transactivated by lineage-specific factors including MITF (in melanocytes) and maintained by the SWI/SNF ATPases BRM/BRG1, with loss of GTF2H1 destabilizing the entire TFIIH complex (including the CDK7-containing CAK subcomplex) and sensitizing cells to UV- and platinum-induced DNA damage.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GTF2H1 encodes the 62-kDa core subunit of the transcription factor IIH (TFIIH) complex, which functions in both RNA polymerase II-dependent transcription and nucleotide excision repair (NER) [#0, #4]. GTF2H1 levels set TFIIH stability and function: depletion of the SWI/SNF ATPases BRM/SMARCA2 or BRG1/SMARCA4 downregulates GTF2H1, compromising TFIIH integrity and rendering SWI/SNF-deficient cells sensitive to UV irradiation and cisplatin in a GTF2H1-dependent manner [#0]. In the melanocytic lineage, MITF directly transactivates GTF2H1, and MITF loss collapses GTF2H1-dependent TFIIH with consequent proteasomal degradation of the CDK7-containing CAK subcomplex, defining a MITF\\u2192GTF2H1\\u2192TFIIH-CAK axis that governs general transcription and UV-induced NER [#1]. Consistent with its NER role, GTF2H1 protein is induced in hepatic cells responding to AZT-induced DNA damage downstream of the recognition factor XPC [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Establishing the molecular identity and genomic position of the gene was the first step, fixing GTF2H1 as the 62-kDa TFIIH subunit and assigning it a chromosomal locus.\",\n      \"evidence\": \"FISH on banded chromosomes with YAC/cosmid physical mapping\",\n      \"pmids\": [\"7789978\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional perturbation linking the locus to TFIIH activity\",\n        \"Provides identity/position but not mechanism in transcription or repair\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether GTF2H1-containing TFIIH participates in the cellular response to a specific DNA-damaging agent was addressed by showing GTF2H1 induction and XPC-dependent NER engagement upon AZT treatment.\",\n      \"evidence\": \"PCR array, Western blot, and shRNA knockdown of XPC with viability/apoptosis assays in HepG2 hepatoma cells\",\n      \"pmids\": [\"21192964\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Pathway placement inferred from XPC epistasis; no GTF2H1-specific perturbation performed\",\n        \"Does not establish whether GTF2H1 induction is functionally required for AZT resistance\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether GTF2H1 induction by AZT extends beyond cancer cells was tested by measuring dose-dependent upregulation in non-transformed hepatic cells.\",\n      \"evidence\": \"PCR array and Western blot across AZT dose range in immortalized THLE2 cells\",\n      \"pmids\": [\"23675285\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single-method protein measurement with no GTF2H1-specific functional perturbation\",\n        \"Corroborative only; adds little new mechanism beyond the prior HepG2 finding\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The question of what maintains GTF2H1 expression and how its level controls TFIIH function was answered by showing SWI/SNF ATPases promote GTF2H1 transcription and that GTF2H1 abundance dictates TFIIH stability and DNA-damage sensitivity.\",\n      \"evidence\": \"RNAi depletion of BRM/BRG1, TFIIH stability and GTF2H1 expression measurement, UV and cisplatin sensitivity assays in SWI/SNF-deficient cancer cells\",\n      \"pmids\": [\"30287812\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct versus indirect transcriptional control of GTF2H1 by SWI/SNF not fully resolved\",\n        \"Whether the same dependency holds across non-cancer cell types untested\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Lineage-specific control of GTF2H1 was established by demonstrating MITF directly transactivates it, defining a regulatory axis in which GTF2H1 loss destabilizes the TFIIH-CAK subcomplex.\",\n      \"evidence\": \"ChIP, transactivation/reporter assays, and MITF depletion with CDK7 stability, NER, and transcription readouts in melanoma cells and in vivo\",\n      \"pmids\": [\"30651597\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Generality of MITF control beyond the melanocytic lineage unknown\",\n        \"Mechanism of CDK7 degradation upon GTF2H1 loss not structurally defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis by which GTF2H1/p62 organizes TFIIH and coordinates the transcription versus NER functions of the complex remains uncharacterized in this corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical reconstitution of p62 within TFIIH in the timeline\",\n        \"Direct enzymatic or scaffolding contribution of GTF2H1 to NER not dissected\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140223\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\"TFIIH\", \"TFIIH-CAK\"],\n    \"partners\": [\"CDK7\", \"MITF\", \"SMARCA2\", \"SMARCA4\", \"XPC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}