{"gene":"VGLL2","run_date":"2026-04-28T23:00:23","timeline":{"discoveries":[{"year":2017,"finding":"VGLL2 physically interacts with TEAD1 and TEAD4 in neonatal skeletal muscle, and Vgll2 null mice show increased fast-twitch type IIb fibers and downregulation of slow type I myosin heavy chain gene (Myh7), with concomitant dysregulation of miR-208b and its targets (Sox6, Sp3, Purβ), establishing VGLL2 as a regulator of slow muscle fiber programming through VGLL2-TEAD complex formation.","method":"Co-immunoprecipitation (physical interaction with TEAD1/4), Vgll2 knockout mouse phenotyping, fiber-type quantification, qPCR for downstream targets","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP plus clean KO mouse with defined cellular phenotype and downstream pathway analysis","pmids":["28769032"],"is_preprint":false},{"year":2019,"finding":"Increased muscle usage elevates VGLL2 levels and promotes interaction between VGLL2 and TEAD1, MEF2c, and NFATc1; calcium ionophore treatment promotes nuclear translocation of VGLL2 and increases TEAD-dependent MYH7 promoter activity in a VGLL2-dependent manner, establishing VGLL2 as an essential regulator of slow-contractile phenotype and oxidative metabolism during chronic overload.","method":"Synergist ablation model in Vgll2-deficient mice, co-immunoprecipitation, luciferase reporter assay (MYH7 promoter), calcium ionophore treatment, nuclear fractionation/localization","journal":"Journal of cellular physiology","confidence":"High","confidence_rationale":"Tier 2 — KO mouse with defined phenotype plus co-IP, promoter reporter, and localization with functional consequence","pmids":["30724341"],"is_preprint":false},{"year":2020,"finding":"Human VGLL2 interacts with TEAD via both a conserved TONDU domain and an additional Ω-loop structural element, unlike VGLL1 and VGLL3 which interact via the TONDU domain alone; this Ω-loop is shared with Drosophila Vg and YAP proteins and contributes to TEAD binding.","method":"Structural analysis of TEAD-binding domains, biochemical binding studies","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1 — structural and biochemical characterization with functional domain delineation","pmids":["33060790"],"is_preprint":false},{"year":2023,"finding":"The VGLL2-NCOA2 fusion protein is sufficient to generate mesenchymal tumors with features of immature skeletal muscle in zebrafish and mouse allograft models; the fusion activates developmental programs including upregulation of the RAS family GTPase ARF6, and ARF6 knockout suppresses VGLL2-NCOA2 oncogenic activity in cell culture, placing ARF6 downstream of the fusion oncogene.","method":"Zebrafish transgenic tumor model, mouse allograft, cell culture ARF6 knockout, RNA sequencing/transcriptomic clustering, patient sample validation","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — cross-species in vivo tumor models with genetic epistasis (ARF6 KO) and multiple orthogonal methods","pmids":["36656711"],"is_preprint":false},{"year":2025,"finding":"VGLL2-NCOA2 and TEAD1-NCOA2 fusion proteins are potent activators of TEAD-dependent transcription independent of YAP/TAZ; they recruit histone acetyltransferase EP300 to control TEAD-mediated transcriptional and epigenetic landscapes, and small-molecule EP300 inhibition suppresses fusion protein-induced oncogenic transformation in vitro and in vivo.","method":"Luciferase reporter assays (TEAD-dependent transcription), Co-IP/pulldown for EP300 recruitment, small-molecule EP300 inhibitor treatment, in vitro transformation assays, in vivo mouse models","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods including reporter assays, co-IP, in vitro and in vivo validation with pharmacological intervention","pmids":["40338073"],"is_preprint":false},{"year":2011,"finding":"Zebrafish vgll2a is expressed in pharyngeal endoderm and ectoderm surrounding neural crest-derived mesenchyme; morpholino knockdown of Vgll2a results in increased cell death in pharyngeal arches, aberrant endodermal pouch morphogenesis, and hypoplastic cranial cartilages, demonstrating a non-cell-autonomous role for Vgll2 in neural crest cell survival and craniofacial development; FGF and retinoic acid signaling regulate vgll2a expression.","method":"Morpholino knockdown in zebrafish, TUNEL (cell death assay), Alcian blue cartilage staining, in situ hybridization, FGF/RA pathway perturbation","journal":"Developmental biology","confidence":"High","confidence_rationale":"Tier 2 — clean morpholino KD in zebrafish ortholog with defined cellular phenotype and pathway regulation confirmed by multiple methods","pmids":["21741961"],"is_preprint":false},{"year":2007,"finding":"Vgll2 is highly expressed in neonatal mouse ventromedial hypothalamus (VMH) and is the highest expressed VMH transcript at postnatal day 0, but is completely absent in older animals, suggesting a role in hypothalamic development; zebrafish knockdown experiments confirmed functional importance of VMH markers including Vgll2.","method":"Gene expression profiling, real-time PCR, Allen Brain Atlas virtual in situ hybridization, zebrafish knockdown","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 3 — expression profiling plus zebrafish knockdown; functional mechanistic detail is limited","pmids":["18077674"],"is_preprint":false},{"year":2024,"finding":"VGLL2 overexpression in mice shifts muscle fiber composition toward slow type, enhances exercise endurance, increases mitochondrial DNA content, protein abundance of oxidative phosphorylation complexes, and maximal respiration in isolated muscle fibers; VGLL2 expression is positively correlated with mitochondrial function genes, establishing VGLL2 as an integrative regulator of mitochondrial function and contractility in skeletal muscle.","method":"Vgll2 transgenic overexpression mouse model, fiber-type quantification, mitochondrial DNA quantification, oxygen consumption rate measurement in isolated fibers, gene expression correlation analysis, exercise testing","journal":"Journal of cellular physiology","confidence":"High","confidence_rationale":"Tier 2 — transgenic overexpression with multiple orthogonal functional readouts including in vitro mitochondrial respiration assay","pmids":["39286968"],"is_preprint":false},{"year":2024,"finding":"Structural analysis of the TEAD-binding domain across more than 2400 VGLL vertebrate proteins shows strong link between sequence conservation and functional role for Tondu motif residues; VGLL2 contains both a Tondu motif and an Ω-loop, with selective pressure to maintain at least one vertebrate VGLL paralog with a functional Ω-loop; some mammalian VGLL2 and VGLL3 variants show altered TEAD-binding domains suggesting divergent function.","method":"Comparative sequence analysis of >2400 VGLL proteins from vertebrates, structural data integration","journal":"Archives of biochemistry and biophysics","confidence":"Medium","confidence_rationale":"Tier 1 for structural analysis, but computational/comparative without new experimental validation — moderate confidence","pmids":["39182750"],"is_preprint":false},{"year":2025,"finding":"VGLL2-NCOA2 and TEAD1-NCOA2 fusion proteins drive YAP/TAZ-independent TEAD-dependent transcription and recruit p300 histone acetyltransferase; p300 small-molecule inhibition suppresses fusion-driven oncogenic transformation both in vitro and in vivo (preprint version of the same study as PMID:40338073).","method":"Reporter assays, Co-IP for p300 recruitment, pharmacological p300 inhibition, in vitro and in vivo mouse transformation models","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — preprint of peer-reviewed study, superseded by published version; included for completeness","pmids":["38746415"],"is_preprint":true}],"current_model":"VGLL2 is a transcriptional cofactor that binds TEAD transcription factors via a conserved TONDU domain plus an additional Ω-loop, forming complexes with TEAD1/4, MEF2c, and NFATc1 in skeletal muscle to drive slow-fiber gene programming (including MYH7 and mitochondrial oxidative capacity) through calcium/nuclear translocation signaling; in oncogenic contexts, VGLL2-NCOA2 fusion proteins potently activate TEAD-dependent transcription in a YAP/TAZ-independent manner by recruiting histone acetyltransferase EP300, and drive sarcomagenesis by reactivating developmental programs including ARF6, which can be therapeutically targeted by EP300 inhibition."},"narrative":{"teleology":[{"year":2007,"claim":"Identifying VGLL2 as a highly expressed neonatal hypothalamic transcript that is absent in mature animals raised the question of whether it functions in developmental transcriptional programs beyond muscle.","evidence":"Gene expression profiling and real-time PCR in postnatal mouse ventromedial hypothalamus with zebrafish knockdown confirmation","pmids":["18077674"],"confidence":"Medium","gaps":["No mechanistic target or binding partner identified in hypothalamic context","Functional consequence of hypothalamic Vgll2 loss not characterized beyond expression loss"]},{"year":2011,"claim":"Demonstrating that zebrafish vgll2a is required non-cell-autonomously for neural crest survival and craniofacial cartilage formation established that VGLL2 functions in developmental signaling beyond muscle, regulated by FGF and retinoic acid pathways.","evidence":"Morpholino knockdown in zebrafish with TUNEL assay, Alcian blue staining, in situ hybridization, and FGF/RA pathway perturbation","pmids":["21741961"],"confidence":"High","gaps":["Transcriptional targets of Vgll2 in pharyngeal endoderm not identified","Whether TEAD is the relevant partner in craniofacial context is untested","Mammalian craniofacial phenotype not examined"]},{"year":2017,"claim":"Establishing that VGLL2 physically interacts with TEAD1/4 and that its loss shifts skeletal muscle toward fast-twitch fibers with downregulation of MYH7 and miR-208b defined the VGLL2-TEAD axis as a core regulator of slow muscle fiber identity.","evidence":"Co-immunoprecipitation with TEAD1/4, Vgll2 knockout mouse phenotyping with fiber-type quantification and qPCR","pmids":["28769032"],"confidence":"High","gaps":["Structural basis of VGLL2-TEAD interaction not yet resolved","Whether VGLL2 directly activates MYH7 promoter or acts indirectly through miR-208b/Sox6 axis unclear"]},{"year":2019,"claim":"Showing that calcium signaling promotes VGLL2 nuclear translocation and that VGLL2 forms complexes with MEF2c and NFATc1 in addition to TEAD1 during chronic overload revealed the signal-dependent activation mechanism coupling muscle use to slow-fiber gene programming.","evidence":"Synergist ablation in Vgll2-deficient mice, co-IP, MYH7 promoter luciferase reporter, calcium ionophore treatment with nuclear fractionation","pmids":["30724341"],"confidence":"High","gaps":["Calcium-dependent kinase or phosphorylation event controlling nuclear import not identified","Relative contribution of TEAD versus MEF2c versus NFATc1 to VGLL2-dependent transcription not dissected"]},{"year":2020,"claim":"Resolving that VGLL2 uses both a TONDU domain and an Ω-loop to bind TEAD — unlike VGLL1/3 which use only the TONDU domain — provided a structural explanation for differential TEAD engagement among VGLL paralogs.","evidence":"Structural and biochemical analysis of TEAD-binding domains","pmids":["33060790"],"confidence":"High","gaps":["Full co-crystal structure of VGLL2-TEAD complex not available","Functional consequence of Ω-loop loss on muscle fiber-type phenotype not tested in vivo"]},{"year":2023,"claim":"Demonstrating that the VGLL2-NCOA2 fusion is sufficient to generate mesenchymal tumors with immature skeletal muscle features and that ARF6 is a critical downstream effector established the oncogenic mechanism of this fusion and identified a therapeutic vulnerability.","evidence":"Zebrafish transgenic and mouse allograft tumor models, ARF6 knockout epistasis in cell culture, RNA-seq with patient sample validation","pmids":["36656711"],"confidence":"High","gaps":["How ARF6 mechanistically promotes transformation downstream of VGLL2-NCOA2 not resolved","Whether wild-type VGLL2 has any role in ARF6 regulation unknown"]},{"year":2024,"claim":"Transgenic overexpression of VGLL2 demonstrating enhanced mitochondrial DNA content, oxidative phosphorylation complex abundance, maximal respiration, and exercise endurance established VGLL2 as an integrative regulator coupling fiber-type identity with mitochondrial bioenergetics.","evidence":"Vgll2 transgenic overexpression mouse with fiber-type quantification, mitochondrial DNA quantification, oxygen consumption measurement in isolated fibers, and exercise testing","pmids":["39286968"],"confidence":"High","gaps":["Direct transcriptional targets driving mitochondrial biogenesis not identified","Whether mitochondrial effects require TEAD or proceed through MEF2c/NFATc1 not determined"]},{"year":2025,"claim":"Identifying EP300 recruitment as the mechanism by which VGLL2-NCOA2 activates TEAD-dependent transcription independently of YAP/TAZ, and showing that EP300 inhibition suppresses fusion-driven transformation, revealed the epigenetic basis of oncogenic VGLL2 fusion activity and a druggable target.","evidence":"Luciferase reporter assays, Co-IP for EP300, small-molecule EP300 inhibitor treatment in vitro and in vivo mouse models","pmids":["40338073"],"confidence":"High","gaps":["Whether EP300 recruitment is relevant to wild-type VGLL2 transcriptional activity unknown","Genome-wide EP300 binding sites specific to VGLL2-NCOA2 versus TEAD1-NCOA2 not distinguished","Clinical efficacy of EP300 inhibition in VGLL2-NCOA2 sarcomas not tested"]},{"year":null,"claim":"The mechanism by which calcium signaling controls VGLL2 nuclear import, the identity of direct VGLL2-TEAD transcriptional targets genome-wide in muscle, and whether wild-type VGLL2 recruits EP300 or other coactivators remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No phosphoproteomics or kinase identification for calcium-dependent VGLL2 nuclear translocation","No ChIP-seq for VGLL2 in normal skeletal muscle","Role of VGLL2 in human craniofacial or hypothalamic development not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[5,6]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[3,4]}],"complexes":[],"partners":["TEAD1","TEAD4","MEF2C","NFATC1","EP300","NCOA2","ARF6"],"other_free_text":[]},"mechanistic_narrative":"VGLL2 is a transcriptional cofactor that partners with TEAD family transcription factors to regulate skeletal muscle fiber-type specification, mitochondrial oxidative capacity, and craniofacial development. It binds TEAD1 and TEAD4 through a conserved TONDU domain and an additional Ω-loop structural element, and forms complexes with MEF2c and NFATc1 in skeletal muscle; calcium signaling promotes its nuclear translocation and activation of TEAD-dependent transcription of slow-fiber genes including MYH7, while Vgll2-null mice exhibit a shift toward fast-twitch fibers and reduced oxidative metabolism, and transgenic overexpression enhances mitochondrial content, respiration, and exercise endurance [PMID:28769032, PMID:30724341, PMID:33060790, PMID:39286968]. In zebrafish, vgll2a functions non-cell-autonomously in pharyngeal endoderm to support neural crest cell survival and craniofacial cartilage morphogenesis downstream of FGF and retinoic acid signaling [PMID:21741961]. In oncogenic contexts, the VGLL2-NCOA2 fusion protein activates TEAD-dependent transcription independently of YAP/TAZ by recruiting histone acetyltransferase EP300, drives sarcomagenesis through reactivation of developmental programs including the GTPase ARF6, and is therapeutically targetable by EP300 small-molecule inhibition [PMID:36656711, PMID:40338073]."},"prefetch_data":{"uniprot":{"accession":"Q8N8G2","full_name":"Transcription cofactor vestigial-like protein 2","aliases":["Protein VITO1"],"length_aa":317,"mass_kda":33.4,"function":"May act as a specific coactivator for the mammalian TEFs. May play a role in the development of skeletal muscles","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8N8G2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VGLL2","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/VGLL2","total_profiled":1310},"omim":[{"mim_id":"609979","title":"VESTIGIAL-LIKE 2; VGLL2","url":"https://www.omim.org/entry/609979"},{"mim_id":"189967","title":"TEA DOMAIN FAMILY MEMBER 1; TEAD1","url":"https://www.omim.org/entry/189967"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"skeletal muscle","ntpm":121.3}],"url":"https://www.proteinatlas.org/search/VGLL2"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q8N8G2","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8G2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8G2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8G2-F1-predicted_aligned_error_v6.png","plddt_mean":54.22},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VGLL2","jax_strain_url":"https://www.jax.org/strain/search?query=VGLL2"},"sequence":{"accession":"Q8N8G2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N8G2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N8G2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8G2"}},"corpus_meta":[{"pmid":"29431183","id":"PMC_29431183","title":"Transcriptomic definition of molecular subgroups of small round cell sarcomas.","date":"2018","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/29431183","citation_count":266,"is_preprint":false},{"pmid":"26501226","id":"PMC_26501226","title":"A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2-related Fusions in Infantile Cases.","date":"2016","source":"The American journal of surgical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26501226","citation_count":204,"is_preprint":false},{"pmid":"30181563","id":"PMC_30181563","title":"MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. 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genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40599543","citation_count":1,"is_preprint":false},{"pmid":"38556817","id":"PMC_38556817","title":"[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].","date":"2024","source":"Zhonghua bing li xue za zhi = Chinese journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/38556817","citation_count":0,"is_preprint":false},{"pmid":"34164773","id":"PMC_34164773","title":"Establishment and characterization of NCC-ssRMS2-C1: a novel patient-derived cell line of spindle cell/sclerosing rhabdomyosarcoma.","date":"2021","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/34164773","citation_count":0,"is_preprint":false},{"pmid":"40300335","id":"PMC_40300335","title":"Vestigial-like family member 1 (VGLL1): An emerging candidate in tumor progression.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/40300335","citation_count":0,"is_preprint":false},{"pmid":"39140953","id":"PMC_39140953","title":"[Genetic architecture of anterior abdominal wall hernias].","date":"2024","source":"Khirurgiia","url":"https://pubmed.ncbi.nlm.nih.gov/39140953","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":22818,"output_tokens":2664,"usd":0.054207},"stage2":{"model":"claude-opus-4-6","input_tokens":5986,"output_tokens":4952,"usd":0.230595},"total_usd":0.284802,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"VGLL2 physically interacts with TEAD1 and TEAD4 in neonatal skeletal muscle, and Vgll2 null mice show increased fast-twitch type IIb fibers and downregulation of slow type I myosin heavy chain gene (Myh7), with concomitant dysregulation of miR-208b and its targets (Sox6, Sp3, Purβ), establishing VGLL2 as a regulator of slow muscle fiber programming through VGLL2-TEAD complex formation.\",\n      \"method\": \"Co-immunoprecipitation (physical interaction with TEAD1/4), Vgll2 knockout mouse phenotyping, fiber-type quantification, qPCR for downstream targets\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP plus clean KO mouse with defined cellular phenotype and downstream pathway analysis\",\n      \"pmids\": [\"28769032\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Increased muscle usage elevates VGLL2 levels and promotes interaction between VGLL2 and TEAD1, MEF2c, and NFATc1; calcium ionophore treatment promotes nuclear translocation of VGLL2 and increases TEAD-dependent MYH7 promoter activity in a VGLL2-dependent manner, establishing VGLL2 as an essential regulator of slow-contractile phenotype and oxidative metabolism during chronic overload.\",\n      \"method\": \"Synergist ablation model in Vgll2-deficient mice, co-immunoprecipitation, luciferase reporter assay (MYH7 promoter), calcium ionophore treatment, nuclear fractionation/localization\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KO mouse with defined phenotype plus co-IP, promoter reporter, and localization with functional consequence\",\n      \"pmids\": [\"30724341\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Human VGLL2 interacts with TEAD via both a conserved TONDU domain and an additional Ω-loop structural element, unlike VGLL1 and VGLL3 which interact via the TONDU domain alone; this Ω-loop is shared with Drosophila Vg and YAP proteins and contributes to TEAD binding.\",\n      \"method\": \"Structural analysis of TEAD-binding domains, biochemical binding studies\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — structural and biochemical characterization with functional domain delineation\",\n      \"pmids\": [\"33060790\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The VGLL2-NCOA2 fusion protein is sufficient to generate mesenchymal tumors with features of immature skeletal muscle in zebrafish and mouse allograft models; the fusion activates developmental programs including upregulation of the RAS family GTPase ARF6, and ARF6 knockout suppresses VGLL2-NCOA2 oncogenic activity in cell culture, placing ARF6 downstream of the fusion oncogene.\",\n      \"method\": \"Zebrafish transgenic tumor model, mouse allograft, cell culture ARF6 knockout, RNA sequencing/transcriptomic clustering, patient sample validation\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — cross-species in vivo tumor models with genetic epistasis (ARF6 KO) and multiple orthogonal methods\",\n      \"pmids\": [\"36656711\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VGLL2-NCOA2 and TEAD1-NCOA2 fusion proteins are potent activators of TEAD-dependent transcription independent of YAP/TAZ; they recruit histone acetyltransferase EP300 to control TEAD-mediated transcriptional and epigenetic landscapes, and small-molecule EP300 inhibition suppresses fusion protein-induced oncogenic transformation in vitro and in vivo.\",\n      \"method\": \"Luciferase reporter assays (TEAD-dependent transcription), Co-IP/pulldown for EP300 recruitment, small-molecule EP300 inhibitor treatment, in vitro transformation assays, in vivo mouse models\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods including reporter assays, co-IP, in vitro and in vivo validation with pharmacological intervention\",\n      \"pmids\": [\"40338073\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Zebrafish vgll2a is expressed in pharyngeal endoderm and ectoderm surrounding neural crest-derived mesenchyme; morpholino knockdown of Vgll2a results in increased cell death in pharyngeal arches, aberrant endodermal pouch morphogenesis, and hypoplastic cranial cartilages, demonstrating a non-cell-autonomous role for Vgll2 in neural crest cell survival and craniofacial development; FGF and retinoic acid signaling regulate vgll2a expression.\",\n      \"method\": \"Morpholino knockdown in zebrafish, TUNEL (cell death assay), Alcian blue cartilage staining, in situ hybridization, FGF/RA pathway perturbation\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean morpholino KD in zebrafish ortholog with defined cellular phenotype and pathway regulation confirmed by multiple methods\",\n      \"pmids\": [\"21741961\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Vgll2 is highly expressed in neonatal mouse ventromedial hypothalamus (VMH) and is the highest expressed VMH transcript at postnatal day 0, but is completely absent in older animals, suggesting a role in hypothalamic development; zebrafish knockdown experiments confirmed functional importance of VMH markers including Vgll2.\",\n      \"method\": \"Gene expression profiling, real-time PCR, Allen Brain Atlas virtual in situ hybridization, zebrafish knockdown\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — expression profiling plus zebrafish knockdown; functional mechanistic detail is limited\",\n      \"pmids\": [\"18077674\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"VGLL2 overexpression in mice shifts muscle fiber composition toward slow type, enhances exercise endurance, increases mitochondrial DNA content, protein abundance of oxidative phosphorylation complexes, and maximal respiration in isolated muscle fibers; VGLL2 expression is positively correlated with mitochondrial function genes, establishing VGLL2 as an integrative regulator of mitochondrial function and contractility in skeletal muscle.\",\n      \"method\": \"Vgll2 transgenic overexpression mouse model, fiber-type quantification, mitochondrial DNA quantification, oxygen consumption rate measurement in isolated fibers, gene expression correlation analysis, exercise testing\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — transgenic overexpression with multiple orthogonal functional readouts including in vitro mitochondrial respiration assay\",\n      \"pmids\": [\"39286968\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Structural analysis of the TEAD-binding domain across more than 2400 VGLL vertebrate proteins shows strong link between sequence conservation and functional role for Tondu motif residues; VGLL2 contains both a Tondu motif and an Ω-loop, with selective pressure to maintain at least one vertebrate VGLL paralog with a functional Ω-loop; some mammalian VGLL2 and VGLL3 variants show altered TEAD-binding domains suggesting divergent function.\",\n      \"method\": \"Comparative sequence analysis of >2400 VGLL proteins from vertebrates, structural data integration\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 for structural analysis, but computational/comparative without new experimental validation — moderate confidence\",\n      \"pmids\": [\"39182750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VGLL2-NCOA2 and TEAD1-NCOA2 fusion proteins drive YAP/TAZ-independent TEAD-dependent transcription and recruit p300 histone acetyltransferase; p300 small-molecule inhibition suppresses fusion-driven oncogenic transformation both in vitro and in vivo (preprint version of the same study as PMID:40338073).\",\n      \"method\": \"Reporter assays, Co-IP for p300 recruitment, pharmacological p300 inhibition, in vitro and in vivo mouse transformation models\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — preprint of peer-reviewed study, superseded by published version; included for completeness\",\n      \"pmids\": [\"38746415\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"VGLL2 is a transcriptional cofactor that binds TEAD transcription factors via a conserved TONDU domain plus an additional Ω-loop, forming complexes with TEAD1/4, MEF2c, and NFATc1 in skeletal muscle to drive slow-fiber gene programming (including MYH7 and mitochondrial oxidative capacity) through calcium/nuclear translocation signaling; in oncogenic contexts, VGLL2-NCOA2 fusion proteins potently activate TEAD-dependent transcription in a YAP/TAZ-independent manner by recruiting histone acetyltransferase EP300, and drive sarcomagenesis by reactivating developmental programs including ARF6, which can be therapeutically targeted by EP300 inhibition.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"VGLL2 is a transcriptional cofactor that partners with TEAD family transcription factors to regulate skeletal muscle fiber-type specification, mitochondrial oxidative capacity, and craniofacial development. It binds TEAD1 and TEAD4 through a conserved TONDU domain and an additional Ω-loop structural element, and forms complexes with MEF2c and NFATc1 in skeletal muscle; calcium signaling promotes its nuclear translocation and activation of TEAD-dependent transcription of slow-fiber genes including MYH7, while Vgll2-null mice exhibit a shift toward fast-twitch fibers and reduced oxidative metabolism, and transgenic overexpression enhances mitochondrial content, respiration, and exercise endurance [PMID:28769032, PMID:30724341, PMID:33060790, PMID:39286968]. In zebrafish, vgll2a functions non-cell-autonomously in pharyngeal endoderm to support neural crest cell survival and craniofacial cartilage morphogenesis downstream of FGF and retinoic acid signaling [PMID:21741961]. In oncogenic contexts, the VGLL2-NCOA2 fusion protein activates TEAD-dependent transcription independently of YAP/TAZ by recruiting histone acetyltransferase EP300, drives sarcomagenesis through reactivation of developmental programs including the GTPase ARF6, and is therapeutically targetable by EP300 small-molecule inhibition [PMID:36656711, PMID:40338073].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying VGLL2 as a highly expressed neonatal hypothalamic transcript that is absent in mature animals raised the question of whether it functions in developmental transcriptional programs beyond muscle.\",\n      \"evidence\": \"Gene expression profiling and real-time PCR in postnatal mouse ventromedial hypothalamus with zebrafish knockdown confirmation\",\n      \"pmids\": [\"18077674\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mechanistic target or binding partner identified in hypothalamic context\", \"Functional consequence of hypothalamic Vgll2 loss not characterized beyond expression loss\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrating that zebrafish vgll2a is required non-cell-autonomously for neural crest survival and craniofacial cartilage formation established that VGLL2 functions in developmental signaling beyond muscle, regulated by FGF and retinoic acid pathways.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish with TUNEL assay, Alcian blue staining, in situ hybridization, and FGF/RA pathway perturbation\",\n      \"pmids\": [\"21741961\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Transcriptional targets of Vgll2 in pharyngeal endoderm not identified\", \"Whether TEAD is the relevant partner in craniofacial context is untested\", \"Mammalian craniofacial phenotype not examined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing that VGLL2 physically interacts with TEAD1/4 and that its loss shifts skeletal muscle toward fast-twitch fibers with downregulation of MYH7 and miR-208b defined the VGLL2-TEAD axis as a core regulator of slow muscle fiber identity.\",\n      \"evidence\": \"Co-immunoprecipitation with TEAD1/4, Vgll2 knockout mouse phenotyping with fiber-type quantification and qPCR\",\n      \"pmids\": [\"28769032\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of VGLL2-TEAD interaction not yet resolved\", \"Whether VGLL2 directly activates MYH7 promoter or acts indirectly through miR-208b/Sox6 axis unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that calcium signaling promotes VGLL2 nuclear translocation and that VGLL2 forms complexes with MEF2c and NFATc1 in addition to TEAD1 during chronic overload revealed the signal-dependent activation mechanism coupling muscle use to slow-fiber gene programming.\",\n      \"evidence\": \"Synergist ablation in Vgll2-deficient mice, co-IP, MYH7 promoter luciferase reporter, calcium ionophore treatment with nuclear fractionation\",\n      \"pmids\": [\"30724341\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Calcium-dependent kinase or phosphorylation event controlling nuclear import not identified\", \"Relative contribution of TEAD versus MEF2c versus NFATc1 to VGLL2-dependent transcription not dissected\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolving that VGLL2 uses both a TONDU domain and an Ω-loop to bind TEAD — unlike VGLL1/3 which use only the TONDU domain — provided a structural explanation for differential TEAD engagement among VGLL paralogs.\",\n      \"evidence\": \"Structural and biochemical analysis of TEAD-binding domains\",\n      \"pmids\": [\"33060790\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full co-crystal structure of VGLL2-TEAD complex not available\", \"Functional consequence of Ω-loop loss on muscle fiber-type phenotype not tested in vivo\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that the VGLL2-NCOA2 fusion is sufficient to generate mesenchymal tumors with immature skeletal muscle features and that ARF6 is a critical downstream effector established the oncogenic mechanism of this fusion and identified a therapeutic vulnerability.\",\n      \"evidence\": \"Zebrafish transgenic and mouse allograft tumor models, ARF6 knockout epistasis in cell culture, RNA-seq with patient sample validation\",\n      \"pmids\": [\"36656711\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How ARF6 mechanistically promotes transformation downstream of VGLL2-NCOA2 not resolved\", \"Whether wild-type VGLL2 has any role in ARF6 regulation unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Transgenic overexpression of VGLL2 demonstrating enhanced mitochondrial DNA content, oxidative phosphorylation complex abundance, maximal respiration, and exercise endurance established VGLL2 as an integrative regulator coupling fiber-type identity with mitochondrial bioenergetics.\",\n      \"evidence\": \"Vgll2 transgenic overexpression mouse with fiber-type quantification, mitochondrial DNA quantification, oxygen consumption measurement in isolated fibers, and exercise testing\",\n      \"pmids\": [\"39286968\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct transcriptional targets driving mitochondrial biogenesis not identified\", \"Whether mitochondrial effects require TEAD or proceed through MEF2c/NFATc1 not determined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying EP300 recruitment as the mechanism by which VGLL2-NCOA2 activates TEAD-dependent transcription independently of YAP/TAZ, and showing that EP300 inhibition suppresses fusion-driven transformation, revealed the epigenetic basis of oncogenic VGLL2 fusion activity and a druggable target.\",\n      \"evidence\": \"Luciferase reporter assays, Co-IP for EP300, small-molecule EP300 inhibitor treatment in vitro and in vivo mouse models\",\n      \"pmids\": [\"40338073\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether EP300 recruitment is relevant to wild-type VGLL2 transcriptional activity unknown\", \"Genome-wide EP300 binding sites specific to VGLL2-NCOA2 versus TEAD1-NCOA2 not distinguished\", \"Clinical efficacy of EP300 inhibition in VGLL2-NCOA2 sarcomas not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which calcium signaling controls VGLL2 nuclear import, the identity of direct VGLL2-TEAD transcriptional targets genome-wide in muscle, and whether wild-type VGLL2 recruits EP300 or other coactivators remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No phosphoproteomics or kinase identification for calcium-dependent VGLL2 nuclear translocation\", \"No ChIP-seq for VGLL2 in normal skeletal muscle\", \"Role of VGLL2 in human craniofacial or hypothalamic development not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0074160\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TEAD1\", \"TEAD4\", \"MEF2C\", \"NFATC1\", \"EP300\", \"NCOA2\", \"ARF6\"],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait — I need to fix the pathway term_id. \"GO:0074160\" is not valid. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"VGLL2 is a transcriptional cofactor that partners with TEAD family transcription factors to regulate skeletal muscle fiber-type specification, mitochondrial oxidative capacity, and craniofacial development. It binds TEAD1 and TEAD4 through a conserved TONDU domain and an additional Ω-loop structural element, and forms complexes with MEF2c and NFATc1 in skeletal muscle; calcium signaling promotes its nuclear translocation and activation of TEAD-dependent transcription of slow-fiber genes including MYH7, while Vgll2-null mice exhibit a shift toward fast-twitch fibers and reduced oxidative metabolism, and transgenic overexpression enhances mitochondrial content, respiration, and exercise endurance [PMID:28769032, PMID:30724341, PMID:33060790, PMID:39286968]. In zebrafish, vgll2a functions non-cell-autonomously in pharyngeal endoderm to support neural crest cell survival and craniofacial cartilage morphogenesis downstream of FGF and retinoic acid signaling [PMID:21741961]. In oncogenic contexts, the VGLL2-NCOA2 fusion protein activates TEAD-dependent transcription independently of YAP/TAZ by recruiting histone acetyltransferase EP300, drives sarcomagenesis through reactivation of developmental programs including the GTPase ARF6, and is therapeutically targetable by EP300 small-molecule inhibition [PMID:36656711, PMID:40338073].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying VGLL2 as a highly expressed neonatal hypothalamic transcript that is absent in mature animals raised the question of whether it functions in developmental transcriptional programs beyond muscle.\",\n      \"evidence\": \"Gene expression profiling and real-time PCR in postnatal mouse ventromedial hypothalamus with zebrafish knockdown confirmation\",\n      \"pmids\": [\"18077674\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mechanistic target or binding partner identified in hypothalamic context\", \"Functional consequence of hypothalamic Vgll2 loss not characterized beyond expression loss\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrating that zebrafish vgll2a is required non-cell-autonomously for neural crest survival and craniofacial cartilage formation established that VGLL2 functions in developmental signaling beyond muscle, regulated by FGF and retinoic acid pathways.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish with TUNEL assay, Alcian blue staining, in situ hybridization, and FGF/RA pathway perturbation\",\n      \"pmids\": [\"21741961\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Transcriptional targets of Vgll2 in pharyngeal endoderm not identified\", \"Whether TEAD is the relevant partner in craniofacial context is untested\", \"Mammalian craniofacial phenotype not examined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing that VGLL2 physically interacts with TEAD1/4 and that its loss shifts skeletal muscle toward fast-twitch fibers with downregulation of MYH7 and miR-208b defined the VGLL2-TEAD axis as a core regulator of slow muscle fiber identity.\",\n      \"evidence\": \"Co-immunoprecipitation with TEAD1/4, Vgll2 knockout mouse phenotyping with fiber-type quantification and qPCR\",\n      \"pmids\": [\"28769032\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of VGLL2-TEAD interaction not yet resolved\", \"Whether VGLL2 directly activates MYH7 promoter or acts indirectly through miR-208b/Sox6 axis unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that calcium signaling promotes VGLL2 nuclear translocation and that VGLL2 forms complexes with MEF2c and NFATc1 in addition to TEAD1 during chronic overload revealed the signal-dependent activation mechanism coupling muscle use to slow-fiber gene programming.\",\n      \"evidence\": \"Synergist ablation in Vgll2-deficient mice, co-IP, MYH7 promoter luciferase reporter, calcium ionophore treatment with nuclear fractionation\",\n      \"pmids\": [\"30724341\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Calcium-dependent kinase or phosphorylation event controlling nuclear import not identified\", \"Relative contribution of TEAD versus MEF2c versus NFATc1 to VGLL2-dependent transcription not dissected\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolving that VGLL2 uses both a TONDU domain and an Ω-loop to bind TEAD — unlike VGLL1/3 which use only the TONDU domain — provided a structural explanation for differential TEAD engagement among VGLL paralogs.\",\n      \"evidence\": \"Structural and biochemical analysis of TEAD-binding domains\",\n      \"pmids\": [\"33060790\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full co-crystal structure of VGLL2-TEAD complex not available\", \"Functional consequence of Ω-loop loss on muscle fiber-type phenotype not tested in vivo\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that the VGLL2-NCOA2 fusion is sufficient to generate mesenchymal tumors with immature skeletal muscle features and that ARF6 is a critical downstream effector established the oncogenic mechanism of this fusion and identified a therapeutic vulnerability.\",\n      \"evidence\": \"Zebrafish transgenic and mouse allograft tumor models, ARF6 knockout epistasis in cell culture, RNA-seq with patient sample validation\",\n      \"pmids\": [\"36656711\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How ARF6 mechanistically promotes transformation downstream of VGLL2-NCOA2 not resolved\", \"Whether wild-type VGLL2 has any role in ARF6 regulation unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Transgenic overexpression of VGLL2 demonstrating enhanced mitochondrial DNA content, oxidative phosphorylation complex abundance, maximal respiration, and exercise endurance established VGLL2 as an integrative regulator coupling fiber-type identity with mitochondrial bioenergetics.\",\n      \"evidence\": \"Vgll2 transgenic overexpression mouse with fiber-type quantification, mitochondrial DNA quantification, oxygen consumption measurement in isolated fibers, and exercise testing\",\n      \"pmids\": [\"39286968\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct transcriptional targets driving mitochondrial biogenesis not identified\", \"Whether mitochondrial effects require TEAD or proceed through MEF2c/NFATc1 not determined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying EP300 recruitment as the mechanism by which VGLL2-NCOA2 activates TEAD-dependent transcription independently of YAP/TAZ, and showing that EP300 inhibition suppresses fusion-driven transformation, revealed the epigenetic basis of oncogenic VGLL2 fusion activity and a druggable target.\",\n      \"evidence\": \"Luciferase reporter assays, Co-IP for EP300, small-molecule EP300 inhibitor treatment in vitro and in vivo mouse models\",\n      \"pmids\": [\"40338073\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether EP300 recruitment is relevant to wild-type VGLL2 transcriptional activity unknown\", \"Genome-wide EP300 binding sites specific to VGLL2-NCOA2 versus TEAD1-NCOA2 not distinguished\", \"Clinical efficacy of EP300 inhibition in VGLL2-NCOA2 sarcomas not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which calcium signaling controls VGLL2 nuclear import, the identity of direct VGLL2-TEAD transcriptional targets genome-wide in muscle, and whether wild-type VGLL2 recruits EP300 or other coactivators remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No phosphoproteomics or kinase identification for calcium-dependent VGLL2 nuclear translocation\", \"No ChIP-seq for VGLL2 in normal skeletal muscle\", \"Role of VGLL2 in human craniofacial or hypothalamic development not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TEAD1\", \"TEAD4\", \"MEF2C\", \"NFATC1\", \"EP300\", \"NCOA2\", \"ARF6\"],\n    \"other_free_text\": []\n  }\n}\n```"}