{"gene":"GTF2A1","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2001,"finding":"ALF (TFIIAalpha/beta-like factor) is a testis-specific counterpart of the large subunit of TFIIA (GTF2A1), expressed in pachytene spermatocytes and haploid spermatids during spermatogenesis; GTF2A1 (TFIIAalpha/beta) gene structure consists of nine exons, paralleling ALF, and both genes are located on human chromosome 2.","method":"Northern analysis, in situ hybridization, Staput sedimentation of germ cells, genomic database analysis, nucleotide/amino acid sequence comparison","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by in situ hybridization and cell fractionation, single lab, multiple orthogonal methods","pmids":["11159353"],"is_preprint":false}],"current_model":"GTF2A1 encodes the large (alpha/beta) subunit of general transcription factor TFIIA, which is required for transcriptional activation from eukaryotic promoters; a testis-specific paralog (ALF) sharing nine-exon gene structure is co-induced with GTF2A1 and other general transcription factors during spermatogenesis and is expressed specifically in pachytene spermatocytes and haploid spermatids."},"narrative":{"mechanistic_narrative":"GTF2A1 encodes the large subunit of the general transcription factor TFIIA (TFIIAalpha/beta), a factor associated with transcription from eukaryotic promoters; its gene is organized into nine exons on human chromosome 2 [PMID:11159353]. During spermatogenesis, GTF2A1 is paralleled by a testis-specific counterpart, ALF (TFIIAalpha/beta-like factor), which shares the nine-exon gene structure and is expressed in pachytene spermatocytes and haploid spermatids [PMID:11159353]. Beyond this paralog and expression relationship established in [PMID:11159353], no further mechanistic detail on GTF2A1 function, partners, or transcriptional activity has been characterized in the available corpus.","teleology":[{"year":2001,"claim":"Established that the general transcription factor large subunit GTF2A1 has a testis-specific paralog (ALF) with conserved gene architecture, framing a germ-cell-specific arm of the basal transcription machinery during spermatogenesis.","evidence":"Northern analysis, in situ hybridization, Staput sedimentation of germ cells, and genomic/sequence comparison defining ALF expression in pachytene spermatocytes and haploid spermatids and the shared nine-exon structure with GTF2A1 on chromosome 2","pmids":["11159353"],"confidence":"Medium","gaps":["Does not establish the biochemical transcriptional activity or promoter targets of GTF2A1 protein itself","Does not define the functional relationship or division of labor between GTF2A1 and ALF in transcription complexes","No structural or interaction data for GTF2A1 within TFIIA"]},{"year":null,"claim":"The direct biochemical role of GTF2A1 in transcription initiation, its protein partners, and its substrates remain uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstitution of GTF2A1-containing TFIIA activity in the timeline","No mapped physical interactions for GTF2A1","No defined target promoters"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TFIIA"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P52655","full_name":"Transcription initiation factor IIA subunit 1","aliases":["General transcription factor IIA subunit 1","TFIIAL","Transcription initiation factor TFIIA 42 kDa subunit","TFIIA-42"],"length_aa":376,"mass_kda":41.5,"function":"TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P52655/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/GTF2A1","classification":"Common Essential","n_dependent_lines":1086,"n_total_lines":1208,"dependency_fraction":0.8990066225165563},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TBP","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/GTF2A1","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":"605358","title":"GENERAL TRANSCRIPTION FACTOR IIA, 1-LIKE; GTF2A1L","url":"https://www.omim.org/entry/605358"},{"mim_id":"605357","title":"STONIN 1; STON1","url":"https://www.omim.org/entry/605357"},{"mim_id":"605045","title":"MEDIATOR COMPLEX SUBUNIT 7; MED7","url":"https://www.omim.org/entry/605045"},{"mim_id":"605044","title":"MEDIATOR COMPLEX SUBUNIT 27; MED27","url":"https://www.omim.org/entry/605044"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GTF2A1"},"hgnc":{"alias_symbol":["TFIIA"],"prev_symbol":[]},"alphafold":{"accession":"P52655","domains":[{"cath_id":"1.10.287.100","chopping":"7-68","consensus_level":"high","plddt":84.3427,"start":7,"end":68},{"cath_id":"2.30.18.10","chopping":"330-374","consensus_level":"high","plddt":93.574,"start":330,"end":374}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P52655","model_url":"https://alphafold.ebi.ac.uk/files/AF-P52655-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P52655-F1-predicted_aligned_error_v6.png","plddt_mean":55.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GTF2A1","jax_strain_url":"https://www.jax.org/strain/search?query=GTF2A1"},"sequence":{"accession":"P52655","fasta_url":"https://rest.uniprot.org/uniprotkb/P52655.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P52655/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P52655"}},"corpus_meta":[{"pmid":"25677060","id":"PMC_25677060","title":"Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons.","date":"2015","source":"Gynecologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/25677060","citation_count":87,"is_preprint":false},{"pmid":"26496084","id":"PMC_26496084","title":"Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26496084","citation_count":49,"is_preprint":false},{"pmid":"11159353","id":"PMC_11159353","title":"TFIIAalpha/beta-like factor is encoded by a germ cell-specific gene whose expression is up-regulated with other general transcription factors during spermatogenesis in the mouse.","date":"2001","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/11159353","citation_count":45,"is_preprint":false},{"pmid":"32365604","id":"PMC_32365604","title":"Genomic Scan for Selection Signature Reveals Fat Deposition in Chinese Indigenous Sheep with Extreme Tail Types.","date":"2020","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/32365604","citation_count":45,"is_preprint":false},{"pmid":"19724865","id":"PMC_19724865","title":"Identification of candidate epigenetic biomarkers for ovarian cancer detection.","date":"2009","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/19724865","citation_count":35,"is_preprint":false},{"pmid":"37132508","id":"PMC_37132508","title":"Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior.","date":"2023","source":"The American journal of surgical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/37132508","citation_count":27,"is_preprint":false},{"pmid":"28291257","id":"PMC_28291257","title":"Integrated transcriptome and methylome analysis in youth at high risk for bipolar disorder: a preliminary analysis.","date":"2017","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/28291257","citation_count":24,"is_preprint":false},{"pmid":"17596959","id":"PMC_17596959","title":"Interaction of polymorphisms in the interleukin 1B-31 and general transcription factor 2A1 genes on the susceptibility to gastric cancer.","date":"2007","source":"Cytokine","url":"https://pubmed.ncbi.nlm.nih.gov/17596959","citation_count":13,"is_preprint":false},{"pmid":"34494299","id":"PMC_34494299","title":"Combined approaches identify known and novel genes associated with sheep litter size and non-seasonal breeding.","date":"2021","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34494299","citation_count":10,"is_preprint":false},{"pmid":"37393655","id":"PMC_37393655","title":"Polymorphism of GTF2A1 gene is associated with litter size in sheep.","date":"2023","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/37393655","citation_count":5,"is_preprint":false},{"pmid":"35532795","id":"PMC_35532795","title":"Discovering biomarkers for hormone-dependent tumors: in silico study on signaling pathways implicated in cell cycle and cytoskeleton regulation.","date":"2022","source":"Molecular genetics and genomics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/35532795","citation_count":1,"is_preprint":false},{"pmid":"41512661","id":"PMC_41512661","title":"Genome-wide association study reveals candidate genes associated with key egg production traits in Langya chickens.","date":"2026","source":"Poultry science","url":"https://pubmed.ncbi.nlm.nih.gov/41512661","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8542,"output_tokens":384,"usd":0.015693,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6611,"output_tokens":871,"usd":0.027415,"stage2_stop_reason":"end_turn"},"total_usd":0.043108,"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\": 2001,\n      \"finding\": \"ALF (TFIIAalpha/beta-like factor) is a testis-specific counterpart of the large subunit of TFIIA (GTF2A1), expressed in pachytene spermatocytes and haploid spermatids during spermatogenesis; GTF2A1 (TFIIAalpha/beta) gene structure consists of nine exons, paralleling ALF, and both genes are located on human chromosome 2.\",\n      \"method\": \"Northern analysis, in situ hybridization, Staput sedimentation of germ cells, genomic database analysis, nucleotide/amino acid sequence comparison\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by in situ hybridization and cell fractionation, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"11159353\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GTF2A1 encodes the large (alpha/beta) subunit of general transcription factor TFIIA, which is required for transcriptional activation from eukaryotic promoters; a testis-specific paralog (ALF) sharing nine-exon gene structure is co-induced with GTF2A1 and other general transcription factors during spermatogenesis and is expressed specifically in pachytene spermatocytes and haploid spermatids.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GTF2A1 encodes the large subunit of the general transcription factor TFIIA (TFIIAalpha/beta), a factor associated with transcription from eukaryotic promoters; its gene is organized into nine exons on human chromosome 2 [#0]. During spermatogenesis, GTF2A1 is paralleled by a testis-specific counterpart, ALF (TFIIAalpha/beta-like factor), which shares the nine-exon gene structure and is expressed in pachytene spermatocytes and haploid spermatids [#0]. Beyond this paralog and expression relationship established in [#0], no further mechanistic detail on GTF2A1 function, partners, or transcriptional activity has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established that the general transcription factor large subunit GTF2A1 has a testis-specific paralog (ALF) with conserved gene architecture, framing a germ-cell-specific arm of the basal transcription machinery during spermatogenesis.\",\n      \"evidence\": \"Northern analysis, in situ hybridization, Staput sedimentation of germ cells, and genomic/sequence comparison defining ALF expression in pachytene spermatocytes and haploid spermatids and the shared nine-exon structure with GTF2A1 on chromosome 2\",\n      \"pmids\": [\"11159353\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not establish the biochemical transcriptional activity or promoter targets of GTF2A1 protein itself\",\n        \"Does not define the functional relationship or division of labor between GTF2A1 and ALF in transcription complexes\",\n        \"No structural or interaction data for GTF2A1 within TFIIA\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical role of GTF2A1 in transcription initiation, its protein partners, and its substrates remain uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution of GTF2A1-containing TFIIA activity in the timeline\",\n        \"No mapped physical interactions for GTF2A1\",\n        \"No defined target promoters\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"TFIIA\"],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":2,"faith_pct":100.0}}