{"gene":"PHF7","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":2012,"finding":"Drosophila PHF7 (ortholog of human PHF7) binds histone H3 N-terminal tails with preference for dimethyl lysine 4 (H3K4me2) via its PHD finger domain, associates with chromatin, and acts as an epigenetic reader to activate the male germline sexual program. Human PHF7 rescues Drosophila Phf7 mutants, demonstrating functional conservation.","method":"Histone tail binding assays, chromatin association, genetic rescue of Drosophila Phf7 mutants with human PHF7, loss-of-function and ectopic expression in Drosophila germline","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal in vivo rescue, direct histone binding assay, multiple orthogonal methods, independently confirmed in subsequent papers","pmids":["22595675"],"is_preprint":false},{"year":2019,"finding":"Mouse PHF7 is a novel E3 ubiquitin ligase for histone H2A: its PHD domain (histone code reader) specifically binds H3K4me3/me2, while its RING domain ubiquitylates H2A. PHF7 can simultaneously bind histone H2A and H3. PHF7 deletion causes aberrant histone retention and impaired protamine replacement in elongated spermatids, leading to male infertility.","method":"In vitro ubiquitination assay, histone binding assays, PHF7 knockout mice with spermiogenesis phenotype analysis","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic assay combined with domain-specific binding assays and knockout mouse phenotype; replicated in subsequent studies","pmids":["31189663"],"is_preprint":false},{"year":2020,"finding":"PHF7 functions as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Its E3 ligase activity on histone ubiquitination stabilizes BRDT (Bromodomain, testis-specific protein) by attenuating ubiquitination of BRDT, thereby enabling histone removal and histone-to-protamine exchange. Phf7 C160A knockin mice with impaired E3 ligase activity phenocopy Phf7-deficient mice.","method":"Phf7 knockout mice, Phf7 C160A knockin mice (E3 ligase-dead), ubiquitination assays, BRDT stability assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1 / Moderate — active-site knockin mutagenesis combined with knockout mouse and biochemical ubiquitination/stability assays in a single study","pmids":["32726616"],"is_preprint":false},{"year":2023,"finding":"Crystal structure of PHF7 in complex with the E2 ubiquitin-conjugating enzyme reveals that the RING domain and C-terminal PHD together capture E2 through direct contact. The N-terminal extended PHD (ePHD) recognizes the nucleosome via DNA binding, while the C-terminal PHD is involved in histone H3 recognition. These three domains make distinct yet collaborative contributions to PHF7 E3 ligase activity.","method":"Crystal structure determination, in vitro binding assays, functional ubiquitination assays with domain mutants","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with functional validation by in vitro binding and ubiquitination assays in a single rigorous study","pmids":["37993255"],"is_preprint":false},{"year":2021,"finding":"PHF7 localizes to cardiac super enhancers in fibroblasts, where it cooperates with the SWI/SNF chromatin remodeling complex to increase chromatin accessibility and transcription factor binding. PHF7 also recruits cardiac transcription factors to activate a positive transcriptional autoregulatory circuit during direct cardiac reprogramming.","method":"Genome-wide chromatin accessibility assays (ATAC-seq), co-immunoprecipitation with SWI/SNF components, transcription factor binding assays, overexpression in adult fibroblasts with reprogramming readout","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP with SWI/SNF, genome-wide chromatin accessibility, and transcription factor binding assays in a single study with multiple orthogonal methods","pmids":["33941892"],"is_preprint":false},{"year":2017,"finding":"Drosophila PHF7 controls spermatogenesis by repressing expression of a novel spermatocyte factor REEPL1 in the spermatogonial stage. Loss of Reepl1 significantly rescues spermatogenesis defects in Phf7 mutants, establishing REEPL1 as an essential downstream target through genetic epistasis.","method":"Transcriptome analysis, genomic profiling of H3K4me2 (PHF7-bound chromatin mark), Phf7 mutant analysis, Reepl1 loss-of-function genetic epistasis","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis (double mutant rescue) combined with transcriptome and ChIP-seq in a single study, Drosophila ortholog","pmids":["28588035"],"is_preprint":false},{"year":2021,"finding":"The evolutionarily novel C-terminus of Drosophila Phf7 is necessary to activate the complete male germline program. The HP1-family protein HP1D3csd acts downstream of Phf7 in the embryonic germline and is required for Phf7 to induce male-like development in female germ cells.","method":"C-terminal deletion constructs of Phf7, transcriptome profiling of FACS-purified embryonic gonads, HP1D3csd loss-of-function combined with Phf7 ectopic expression","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain-deletion constructs with in vivo sex reversal assay and genetic epistasis, single lab","pmids":["33737548"],"is_preprint":false},{"year":2020,"finding":"Ectopic PHF7 in Drosophila female germ cells activates a positive autoregulatory feedback mechanism in which PHF7 overcomes its own transcriptional repression through promoter switching. Tumorigenic capacity in female germ cells is dependent on PHF7 dosage. PHF7 acts in a tissue-specific manner, controlling different gene sets in male versus female germ cells.","method":"Transcriptome analysis of PHF7-expressing ovarian germ cells, promoter analysis, dosage experiments with graded PHF7 expression","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — transcriptome-wide analysis combined with promoter switching and dosage experiments, single lab","pmids":["32816970"],"is_preprint":false},{"year":2002,"finding":"Human PHF7 (NYD-SP6) protein localizes predominantly to the nucleus of transfected CHO cells, whereas the N-terminal truncated form localizes to the nuclear envelope, identifying the N-terminal region as a nuclear localization signal.","method":"GFP fusion protein transfection in CHO cells, fluorescence microscopy, N-terminal truncation construct","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single localization experiment with truncation in heterologous cells, no functional follow-up","pmids":["11829468"],"is_preprint":false},{"year":2023,"finding":"Loss of Phf7 in mouse spermiogenesis activates endogenous retrovirus (ERV)-mediated immune pathways. PPARα was identified as a regulator of ERV-mediated immunity in the testis, and the PPARα agonist astaxanthin rescues the spermatogenesis defect caused by Phf7 deletion, placing PHF7 upstream of ERV suppression and immune regulation during spermiogenesis.","method":"Phf7 knockout mouse model, transcriptome analysis, PPARα agonist rescue experiment","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — knockout mouse with transcriptome and pharmacological rescue, single lab, single study","pmids":["37920670"],"is_preprint":false},{"year":2024,"finding":"Phf7 deficiency in male mice reduces testicular testosterone and dihydrotestosterone production, associated with decreased expression of steroidogenesis marker genes (Star, Cyp11a1, Cyp17a1, 17β-hsd), and leads to increased osteoclast activity (elevated Trap expression) and impaired bone remodeling.","method":"Phf7 knockout mice, hormone level measurement, bone histomorphometry, RT-PCR for steroidogenesis marker genes","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — phenotypic characterization of knockout mice with correlative mRNA measurements, no direct mechanistic link established","pmids":["38430697"],"is_preprint":false},{"year":2025,"finding":"PHF7 as a single factor induces fibroblast-to-cardiomyocyte reprogramming in vivo, alters chromatin structure genome-wide, and upregulates cardiac master regulators (including Tbx5, Mef2c targets) when overexpressed in dermal fibroblasts. Multiomics (single-nucleus transcriptomics + epigenomics) revealed population-level shifts in cellular identity driven by PHF7-induced chromatin remodeling.","method":"In vitro transcriptomics, genome-wide chromatin accessibility (multiomics), in vivo retroviral delivery to infarcted mouse heart with genetic fibroblast lineage tracing, 10X single-nucleus multiomics","journal":"Circulation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide epigenomics and transcriptomics with in vivo genetic lineage tracing, single lab, extends prior mechanistic findings","pmids":["40631661"],"is_preprint":false}],"current_model":"PHF7 is a conserved epigenetic reader-writer protein that uses its PHD domain(s) to recognize H3K4me2/me3 marks on chromatin and its RING domain to ubiquitylate histone H2A (and H3K14), with structural studies showing that E2 recruitment requires cooperative engagement of the RING domain and C-terminal PHD, the ePHD anchors PHF7 to the nucleosome via DNA binding, and in the mammalian testis PHF7 promotes histone-to-protamine exchange by stabilizing the histone-removal factor BRDT; beyond the germline, PHF7 cooperates with the SWI/SNF complex at super enhancers to remodel chromatin and recruit cardiac transcription factors, enabling direct reprogramming of fibroblasts to cardiomyocytes."},"narrative":{"mechanistic_narrative":"PHF7 is a conserved chromatin-associated epigenetic reader-writer that couples recognition of active histone methylation marks to histone ubiquitylation, governing germline sexual development and chromatin remodeling [PMID:22595675, PMID:31189663]. Its PHD finger reads H3K4me2/me3 and anchors PHF7 to chromatin, a function conserved from Drosophila — where it acts as an epigenetic reader activating the male germline program — to humans, which rescue Drosophila Phf7 mutants [PMID:22595675, PMID:31189663]. PHF7 is also a RING-type E3 ubiquitin ligase that ubiquitylates histone H2A and H3K14; structural work shows that productive E2 recruitment requires cooperative engagement of the RING domain and the C-terminal PHD, while the N-terminal extended PHD binds nucleosomal DNA to anchor the enzyme [PMID:31189663, PMID:32726616, PMID:37993255]. In the mammalian testis, this ligase activity drives histone-to-protamine exchange during spermiogenesis: PHF7 stabilizes the histone-removal factor BRDT by attenuating its ubiquitylation, and catalytically dead C160A knockin mice phenocopy the histone-retention infertility of knockouts [PMID:32726616]. Beyond the germline, PHF7 localizes to cardiac super enhancers, cooperates with the SWI/SNF complex to open chromatin and recruit cardiac transcription factors, and acts as a single-factor driver of fibroblast-to-cardiomyocyte reprogramming [PMID:33941892, PMID:40631661].","teleology":[{"year":2002,"claim":"Established the subcellular compartment in which PHF7 acts, identifying it as a nuclear protein dependent on an N-terminal localization signal.","evidence":"GFP-fusion transfection and N-terminal truncation in CHO cells","pmids":["11829468"],"confidence":"Medium","gaps":["Heterologous overexpression system, no endogenous validation","No functional role assigned","Localization signal mapped only by truncation, not point mutation"]},{"year":2012,"claim":"Defined PHF7 as an epigenetic reader that recognizes H3K4me2 and activates the male germline sexual program, with cross-species rescue establishing functional conservation between fly and human orthologs.","evidence":"Histone tail binding assays, chromatin association, and genetic rescue of Drosophila Phf7 mutants with human PHF7","pmids":["22595675"],"confidence":"High","gaps":["No catalytic activity yet identified","Downstream gene targets not defined","Reader-to-output mechanism unresolved"]},{"year":2017,"claim":"Connected PHF7 chromatin binding to a concrete transcriptional output by identifying REEPL1 as a repressed downstream target required for the spermatogenesis phenotype.","evidence":"Transcriptome and H3K4me2 profiling with Reepl1 loss-of-function genetic epistasis in Drosophila","pmids":["28588035"],"confidence":"Medium","gaps":["Mechanism of REEPL1 repression not defined","Drosophila ortholog only","Direct vs indirect regulation unresolved"]},{"year":2019,"claim":"Reclassified PHF7 from a pure reader to a reader-writer by demonstrating RING-domain E3 ubiquitin ligase activity toward histone H2A, linking it mechanistically to histone retention and protamine replacement in spermatids.","evidence":"In vitro ubiquitination and domain-specific binding assays with PHF7 knockout mouse spermiogenesis analysis","pmids":["31189663"],"confidence":"High","gaps":["Substrate range beyond H2A not delineated","How ubiquitylation drives histone removal not yet mechanistic"]},{"year":2020,"claim":"Defined the molecular route from PHF7 ligase activity to histone eviction, showing it stabilizes BRDT by attenuating its ubiquitylation, with active-site knockin proving catalysis is required in vivo.","evidence":"Phf7 C160A ligase-dead knockin and knockout mice with ubiquitination and BRDT stability assays","pmids":["32726616"],"confidence":"High","gaps":["Direct vs indirect effect on BRDT ubiquitylation not fully resolved","H3K14 ubiquitylation consequences beyond BRDT unclear"]},{"year":2020,"claim":"Revealed PHF7 dosage-dependent autoregulation and tissue-specific gene control, showing it overcomes its own repression via promoter switching and confers tumorigenic capacity in female germ cells.","evidence":"Transcriptome, promoter, and graded-dosage expression analyses in Drosophila germ cells","pmids":["32816970"],"confidence":"Medium","gaps":["Mechanism of promoter switching not defined","Drosophila-specific","Relevance of autoregulation to mammals untested"]},{"year":2021,"claim":"Mapped the evolutionarily novel C-terminus as required for the complete male program and placed the HP1-family protein HP1D3csd downstream of Phf7 in germline sex determination.","evidence":"C-terminal deletion constructs and HP1D3csd loss-of-function with Phf7 ectopic expression in Drosophila","pmids":["33737548"],"confidence":"Medium","gaps":["Biochemical role of C-terminus not defined","HP1D3csd-PHF7 relationship genetic not physical"]},{"year":2021,"claim":"Extended PHF7 function beyond the germline, showing it operates at cardiac super enhancers with the SWI/SNF complex to increase chromatin accessibility and recruit cardiac transcription factors during direct reprogramming.","evidence":"ATAC-seq, co-IP with SWI/SNF components, and transcription factor binding assays in reprogramming fibroblasts","pmids":["33941892"],"confidence":"High","gaps":["Whether ligase activity is required for cardiac function untested","Direct SWI/SNF contact vs co-recruitment unresolved"]},{"year":2023,"claim":"Provided the structural basis for PHF7 catalysis, showing the RING and C-terminal PHD cooperatively capture E2 while the N-terminal ePHD anchors the nucleosome via DNA binding.","evidence":"Crystal structure of PHF7-E2 complex with domain-mutant binding and ubiquitination assays","pmids":["37993255"],"confidence":"High","gaps":["Full nucleosome-bound structure not resolved","Coupling of reader to ligase output not visualized"]},{"year":2023,"claim":"Linked PHF7 loss to derepression of endogenous retroviruses and immune activation, identifying PPARα signaling as a pharmacologically actionable node downstream of PHF7 in the testis.","evidence":"Phf7 knockout transcriptomics with PPARα agonist (astaxanthin) rescue","pmids":["37920670"],"confidence":"Medium","gaps":["Direct mechanism of ERV suppression by PHF7 not defined","PPARα-PHF7 link correlative","Single study"]},{"year":2024,"claim":"Associated Phf7 deficiency with reduced testicular steroidogenesis and downstream bone remodeling defects, hinting at an endocrine consequence of germline dysfunction.","evidence":"Phf7 knockout mice with hormone measurement, bone histomorphometry, and steroidogenesis marker RT-PCR","pmids":["38430697"],"confidence":"Low","gaps":["No direct mechanistic link between PHF7 and steroidogenic gene regulation","Correlative mRNA measurements only","Bone phenotype likely secondary to hormone loss"]},{"year":2025,"claim":"Demonstrated PHF7 alone can reprogram fibroblasts to cardiomyocytes in vivo through genome-wide chromatin remodeling and upregulation of cardiac master regulators, consolidating its role as a single-factor reprogramming driver.","evidence":"Single-nucleus multiomics, in vitro transcriptomics, and in vivo retroviral delivery with fibroblast lineage tracing in infarcted mouse heart","pmids":["40631661"],"confidence":"Medium","gaps":["Whether E3 ligase activity is required for reprogramming untested","Mechanism of chromatin remodeling beyond accessibility shifts unclear","Single lab"]},{"year":null,"claim":"How PHF7's reader function, E3 ligase activity, and SWI/SNF cooperation are mechanistically integrated across the distinct germline and cardiac reprogramming contexts remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Whether catalytic activity is required outside spermiogenesis is untested","Full substrate repertoire beyond H2A and H3K14 is undefined","No structure of PHF7 engaging both nucleosome and SWI/SNF"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[1,2,3]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1,2]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[3]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[8]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0,1,4]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,1,4]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[4,11]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["BRDT","SWI/SNF"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BWX1","full_name":"E3 ubiquitin-protein ligase PHF7","aliases":["PHD finger protein 7","Testis development protein NYD-SP6"],"length_aa":381,"mass_kda":43.8,"function":"E3 ubiquitin-protein ligase which ubiquitinates histone H3 at 'Lys-14' (By similarity). Required for male fertility, via inhibition of SPOP-mediated BRDT degradation when in the presence of acetylated histone H4 in early condensing spermatids (By similarity). Stabilization of BRDT allows it to facilitate histone removal in early condensing spermatids and promote the progression of histone-to-protamine exchange (By similarity). Promotes the expression of steroidogenesis proteins in the testes, and as a result plays a role in maintaining testosterone levels and repressing osteoclastogenesis (By similarity). Promotes transcription of cardiac enhancer genes by facilitating binding of cardiac transcription factors such as MEF2C and GATA4 to target gene promoters (By similarity). Ubiquitinates histone H4 (PubMed:32726616). Ubiquitinates histone H2A and H3 as part of the nucleosome core particle (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9BWX1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PHF7","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PHF7","total_profiled":1310},"omim":[{"mim_id":"620057","title":"PHD FINGER PROTEIN 7; PHF7","url":"https://www.omim.org/entry/620057"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nuclear speckles","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":1149.0}],"url":"https://www.proteinatlas.org/search/PHF7"},"hgnc":{"alias_symbol":["NYD-SP6","HSPC226"],"prev_symbol":[]},"alphafold":{"accession":"Q9BWX1","domains":[{"cath_id":"3.30.40.10","chopping":"48-139","consensus_level":"high","plddt":93.991,"start":48,"end":139},{"cath_id":"3.30.40","chopping":"158-231","consensus_level":"high","plddt":92.437,"start":158,"end":231},{"cath_id":"3.30.40.10","chopping":"244-303","consensus_level":"medium","plddt":91.02,"start":244,"end":303}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWX1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWX1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWX1-F1-predicted_aligned_error_v6.png","plddt_mean":76.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PHF7","jax_strain_url":"https://www.jax.org/strain/search?query=PHF7"},"sequence":{"accession":"Q9BWX1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BWX1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BWX1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWX1"}},"corpus_meta":[{"pmid":"22595675","id":"PMC_22595675","title":"Phf7 controls male sex determination in the Drosophila germline.","date":"2012","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/22595675","citation_count":65,"is_preprint":false},{"pmid":"33941892","id":"PMC_33941892","title":"The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming.","date":"2021","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/33941892","citation_count":59,"is_preprint":false},{"pmid":"31189663","id":"PMC_31189663","title":"PHF7 is a novel histone H2A E3 ligase prior to histone-to-protamine exchange during spermiogenesis.","date":"2019","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/31189663","citation_count":53,"is_preprint":false},{"pmid":"32726616","id":"PMC_32726616","title":"PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/32726616","citation_count":37,"is_preprint":false},{"pmid":"11829468","id":"PMC_11829468","title":"NYD-SP6, a novel gene potentially involved in regulating testicular development/spermatogenesis.","date":"2002","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/11829468","citation_count":23,"is_preprint":false},{"pmid":"28912601","id":"PMC_28912601","title":"PHF7, a novel male gene influences female fecundity and population growth in Nilaparvata lugens Stål (Hemiptera: Delphacidae).","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28912601","citation_count":15,"is_preprint":false},{"pmid":"28588035","id":"PMC_28588035","title":"Control of a Novel Spermatocyte-Promoting Factor by the Male Germline Sex Determination Factor PHF7 of Drosophila melanogaster.","date":"2017","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28588035","citation_count":15,"is_preprint":false},{"pmid":"37993255","id":"PMC_37993255","title":"Molecular basis for PHF7-mediated ubiquitination of histone H3.","date":"2023","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/37993255","citation_count":7,"is_preprint":false},{"pmid":"32816970","id":"PMC_32816970","title":"An autoregulatory switch in sex-specific phf7 transcription causes loss of sexual identity and tumors in the Drosophila female germline.","date":"2020","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/32816970","citation_count":7,"is_preprint":false},{"pmid":"40631661","id":"PMC_40631661","title":"Cellular Reprogramming by PHF7 Enhances Cardiac Function Following Myocardial Infarction.","date":"2025","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/40631661","citation_count":5,"is_preprint":false},{"pmid":"33737548","id":"PMC_33737548","title":"Germline masculinization by Phf7 in D. melanogaster requires its evolutionarily novel C-terminus and the HP1-family protein HP1D3csd.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33737548","citation_count":5,"is_preprint":false},{"pmid":"35716824","id":"PMC_35716824","title":"Expanding duplication of the testis PHD Finger Protein 7 (PHF7) gene in the chicken genome.","date":"2022","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35716824","citation_count":4,"is_preprint":false},{"pmid":"38430697","id":"PMC_38430697","title":"Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.","date":"2024","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/38430697","citation_count":1,"is_preprint":false},{"pmid":"37920670","id":"PMC_37920670","title":"Loss of histone reader Phf7 leads to immune pathways activation via endogenous retroviruses during spermiogenesis.","date":"2023","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/37920670","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8508,"output_tokens":3138,"usd":0.036297,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10593,"output_tokens":4084,"usd":0.077533,"stage2_stop_reason":"end_turn"},"total_usd":0.11383,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"Drosophila PHF7 (ortholog of human PHF7) binds histone H3 N-terminal tails with preference for dimethyl lysine 4 (H3K4me2) via its PHD finger domain, associates with chromatin, and acts as an epigenetic reader to activate the male germline sexual program. Human PHF7 rescues Drosophila Phf7 mutants, demonstrating functional conservation.\",\n      \"method\": \"Histone tail binding assays, chromatin association, genetic rescue of Drosophila Phf7 mutants with human PHF7, loss-of-function and ectopic expression in Drosophila germline\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal in vivo rescue, direct histone binding assay, multiple orthogonal methods, independently confirmed in subsequent papers\",\n      \"pmids\": [\"22595675\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Mouse PHF7 is a novel E3 ubiquitin ligase for histone H2A: its PHD domain (histone code reader) specifically binds H3K4me3/me2, while its RING domain ubiquitylates H2A. PHF7 can simultaneously bind histone H2A and H3. PHF7 deletion causes aberrant histone retention and impaired protamine replacement in elongated spermatids, leading to male infertility.\",\n      \"method\": \"In vitro ubiquitination assay, histone binding assays, PHF7 knockout mice with spermiogenesis phenotype analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic assay combined with domain-specific binding assays and knockout mouse phenotype; replicated in subsequent studies\",\n      \"pmids\": [\"31189663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PHF7 functions as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Its E3 ligase activity on histone ubiquitination stabilizes BRDT (Bromodomain, testis-specific protein) by attenuating ubiquitination of BRDT, thereby enabling histone removal and histone-to-protamine exchange. Phf7 C160A knockin mice with impaired E3 ligase activity phenocopy Phf7-deficient mice.\",\n      \"method\": \"Phf7 knockout mice, Phf7 C160A knockin mice (E3 ligase-dead), ubiquitination assays, BRDT stability assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site knockin mutagenesis combined with knockout mouse and biochemical ubiquitination/stability assays in a single study\",\n      \"pmids\": [\"32726616\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Crystal structure of PHF7 in complex with the E2 ubiquitin-conjugating enzyme reveals that the RING domain and C-terminal PHD together capture E2 through direct contact. The N-terminal extended PHD (ePHD) recognizes the nucleosome via DNA binding, while the C-terminal PHD is involved in histone H3 recognition. These three domains make distinct yet collaborative contributions to PHF7 E3 ligase activity.\",\n      \"method\": \"Crystal structure determination, in vitro binding assays, functional ubiquitination assays with domain mutants\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with functional validation by in vitro binding and ubiquitination assays in a single rigorous study\",\n      \"pmids\": [\"37993255\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PHF7 localizes to cardiac super enhancers in fibroblasts, where it cooperates with the SWI/SNF chromatin remodeling complex to increase chromatin accessibility and transcription factor binding. PHF7 also recruits cardiac transcription factors to activate a positive transcriptional autoregulatory circuit during direct cardiac reprogramming.\",\n      \"method\": \"Genome-wide chromatin accessibility assays (ATAC-seq), co-immunoprecipitation with SWI/SNF components, transcription factor binding assays, overexpression in adult fibroblasts with reprogramming readout\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP with SWI/SNF, genome-wide chromatin accessibility, and transcription factor binding assays in a single study with multiple orthogonal methods\",\n      \"pmids\": [\"33941892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Drosophila PHF7 controls spermatogenesis by repressing expression of a novel spermatocyte factor REEPL1 in the spermatogonial stage. Loss of Reepl1 significantly rescues spermatogenesis defects in Phf7 mutants, establishing REEPL1 as an essential downstream target through genetic epistasis.\",\n      \"method\": \"Transcriptome analysis, genomic profiling of H3K4me2 (PHF7-bound chromatin mark), Phf7 mutant analysis, Reepl1 loss-of-function genetic epistasis\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis (double mutant rescue) combined with transcriptome and ChIP-seq in a single study, Drosophila ortholog\",\n      \"pmids\": [\"28588035\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The evolutionarily novel C-terminus of Drosophila Phf7 is necessary to activate the complete male germline program. The HP1-family protein HP1D3csd acts downstream of Phf7 in the embryonic germline and is required for Phf7 to induce male-like development in female germ cells.\",\n      \"method\": \"C-terminal deletion constructs of Phf7, transcriptome profiling of FACS-purified embryonic gonads, HP1D3csd loss-of-function combined with Phf7 ectopic expression\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain-deletion constructs with in vivo sex reversal assay and genetic epistasis, single lab\",\n      \"pmids\": [\"33737548\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Ectopic PHF7 in Drosophila female germ cells activates a positive autoregulatory feedback mechanism in which PHF7 overcomes its own transcriptional repression through promoter switching. Tumorigenic capacity in female germ cells is dependent on PHF7 dosage. PHF7 acts in a tissue-specific manner, controlling different gene sets in male versus female germ cells.\",\n      \"method\": \"Transcriptome analysis of PHF7-expressing ovarian germ cells, promoter analysis, dosage experiments with graded PHF7 expression\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transcriptome-wide analysis combined with promoter switching and dosage experiments, single lab\",\n      \"pmids\": [\"32816970\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Human PHF7 (NYD-SP6) protein localizes predominantly to the nucleus of transfected CHO cells, whereas the N-terminal truncated form localizes to the nuclear envelope, identifying the N-terminal region as a nuclear localization signal.\",\n      \"method\": \"GFP fusion protein transfection in CHO cells, fluorescence microscopy, N-terminal truncation construct\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization experiment with truncation in heterologous cells, no functional follow-up\",\n      \"pmids\": [\"11829468\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Loss of Phf7 in mouse spermiogenesis activates endogenous retrovirus (ERV)-mediated immune pathways. PPARα was identified as a regulator of ERV-mediated immunity in the testis, and the PPARα agonist astaxanthin rescues the spermatogenesis defect caused by Phf7 deletion, placing PHF7 upstream of ERV suppression and immune regulation during spermiogenesis.\",\n      \"method\": \"Phf7 knockout mouse model, transcriptome analysis, PPARα agonist rescue experiment\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — knockout mouse with transcriptome and pharmacological rescue, single lab, single study\",\n      \"pmids\": [\"37920670\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Phf7 deficiency in male mice reduces testicular testosterone and dihydrotestosterone production, associated with decreased expression of steroidogenesis marker genes (Star, Cyp11a1, Cyp17a1, 17β-hsd), and leads to increased osteoclast activity (elevated Trap expression) and impaired bone remodeling.\",\n      \"method\": \"Phf7 knockout mice, hormone level measurement, bone histomorphometry, RT-PCR for steroidogenesis marker genes\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — phenotypic characterization of knockout mice with correlative mRNA measurements, no direct mechanistic link established\",\n      \"pmids\": [\"38430697\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PHF7 as a single factor induces fibroblast-to-cardiomyocyte reprogramming in vivo, alters chromatin structure genome-wide, and upregulates cardiac master regulators (including Tbx5, Mef2c targets) when overexpressed in dermal fibroblasts. Multiomics (single-nucleus transcriptomics + epigenomics) revealed population-level shifts in cellular identity driven by PHF7-induced chromatin remodeling.\",\n      \"method\": \"In vitro transcriptomics, genome-wide chromatin accessibility (multiomics), in vivo retroviral delivery to infarcted mouse heart with genetic fibroblast lineage tracing, 10X single-nucleus multiomics\",\n      \"journal\": \"Circulation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide epigenomics and transcriptomics with in vivo genetic lineage tracing, single lab, extends prior mechanistic findings\",\n      \"pmids\": [\"40631661\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PHF7 is a conserved epigenetic reader-writer protein that uses its PHD domain(s) to recognize H3K4me2/me3 marks on chromatin and its RING domain to ubiquitylate histone H2A (and H3K14), with structural studies showing that E2 recruitment requires cooperative engagement of the RING domain and C-terminal PHD, the ePHD anchors PHF7 to the nucleosome via DNA binding, and in the mammalian testis PHF7 promotes histone-to-protamine exchange by stabilizing the histone-removal factor BRDT; beyond the germline, PHF7 cooperates with the SWI/SNF complex at super enhancers to remodel chromatin and recruit cardiac transcription factors, enabling direct reprogramming of fibroblasts to cardiomyocytes.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PHF7 is a conserved chromatin-associated epigenetic reader-writer that couples recognition of active histone methylation marks to histone ubiquitylation, governing germline sexual development and chromatin remodeling [#0, #1]. Its PHD finger reads H3K4me2/me3 and anchors PHF7 to chromatin, a function conserved from Drosophila — where it acts as an epigenetic reader activating the male germline program — to humans, which rescue Drosophila Phf7 mutants [#0, #1]. PHF7 is also a RING-type E3 ubiquitin ligase that ubiquitylates histone H2A and H3K14; structural work shows that productive E2 recruitment requires cooperative engagement of the RING domain and the C-terminal PHD, while the N-terminal extended PHD binds nucleosomal DNA to anchor the enzyme [#1, #2, #3]. In the mammalian testis, this ligase activity drives histone-to-protamine exchange during spermiogenesis: PHF7 stabilizes the histone-removal factor BRDT by attenuating its ubiquitylation, and catalytically dead C160A knockin mice phenocopy the histone-retention infertility of knockouts [#2]. Beyond the germline, PHF7 localizes to cardiac super enhancers, cooperates with the SWI/SNF complex to open chromatin and recruit cardiac transcription factors, and acts as a single-factor driver of fibroblast-to-cardiomyocyte reprogramming [#4, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established the subcellular compartment in which PHF7 acts, identifying it as a nuclear protein dependent on an N-terminal localization signal.\",\n      \"evidence\": \"GFP-fusion transfection and N-terminal truncation in CHO cells\",\n      \"pmids\": [\"11829468\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Heterologous overexpression system, no endogenous validation\", \"No functional role assigned\", \"Localization signal mapped only by truncation, not point mutation\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defined PHF7 as an epigenetic reader that recognizes H3K4me2 and activates the male germline sexual program, with cross-species rescue establishing functional conservation between fly and human orthologs.\",\n      \"evidence\": \"Histone tail binding assays, chromatin association, and genetic rescue of Drosophila Phf7 mutants with human PHF7\",\n      \"pmids\": [\"22595675\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No catalytic activity yet identified\", \"Downstream gene targets not defined\", \"Reader-to-output mechanism unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected PHF7 chromatin binding to a concrete transcriptional output by identifying REEPL1 as a repressed downstream target required for the spermatogenesis phenotype.\",\n      \"evidence\": \"Transcriptome and H3K4me2 profiling with Reepl1 loss-of-function genetic epistasis in Drosophila\",\n      \"pmids\": [\"28588035\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism of REEPL1 repression not defined\", \"Drosophila ortholog only\", \"Direct vs indirect regulation unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Reclassified PHF7 from a pure reader to a reader-writer by demonstrating RING-domain E3 ubiquitin ligase activity toward histone H2A, linking it mechanistically to histone retention and protamine replacement in spermatids.\",\n      \"evidence\": \"In vitro ubiquitination and domain-specific binding assays with PHF7 knockout mouse spermiogenesis analysis\",\n      \"pmids\": [\"31189663\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Substrate range beyond H2A not delineated\", \"How ubiquitylation drives histone removal not yet mechanistic\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined the molecular route from PHF7 ligase activity to histone eviction, showing it stabilizes BRDT by attenuating its ubiquitylation, with active-site knockin proving catalysis is required in vivo.\",\n      \"evidence\": \"Phf7 C160A ligase-dead knockin and knockout mice with ubiquitination and BRDT stability assays\",\n      \"pmids\": [\"32726616\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct vs indirect effect on BRDT ubiquitylation not fully resolved\", \"H3K14 ubiquitylation consequences beyond BRDT unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Revealed PHF7 dosage-dependent autoregulation and tissue-specific gene control, showing it overcomes its own repression via promoter switching and confers tumorigenic capacity in female germ cells.\",\n      \"evidence\": \"Transcriptome, promoter, and graded-dosage expression analyses in Drosophila germ cells\",\n      \"pmids\": [\"32816970\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism of promoter switching not defined\", \"Drosophila-specific\", \"Relevance of autoregulation to mammals untested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Mapped the evolutionarily novel C-terminus as required for the complete male program and placed the HP1-family protein HP1D3csd downstream of Phf7 in germline sex determination.\",\n      \"evidence\": \"C-terminal deletion constructs and HP1D3csd loss-of-function with Phf7 ectopic expression in Drosophila\",\n      \"pmids\": [\"33737548\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Biochemical role of C-terminus not defined\", \"HP1D3csd-PHF7 relationship genetic not physical\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended PHF7 function beyond the germline, showing it operates at cardiac super enhancers with the SWI/SNF complex to increase chromatin accessibility and recruit cardiac transcription factors during direct reprogramming.\",\n      \"evidence\": \"ATAC-seq, co-IP with SWI/SNF components, and transcription factor binding assays in reprogramming fibroblasts\",\n      \"pmids\": [\"33941892\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether ligase activity is required for cardiac function untested\", \"Direct SWI/SNF contact vs co-recruitment unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Provided the structural basis for PHF7 catalysis, showing the RING and C-terminal PHD cooperatively capture E2 while the N-terminal ePHD anchors the nucleosome via DNA binding.\",\n      \"evidence\": \"Crystal structure of PHF7-E2 complex with domain-mutant binding and ubiquitination assays\",\n      \"pmids\": [\"37993255\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Full nucleosome-bound structure not resolved\", \"Coupling of reader to ligase output not visualized\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Linked PHF7 loss to derepression of endogenous retroviruses and immune activation, identifying PPARα signaling as a pharmacologically actionable node downstream of PHF7 in the testis.\",\n      \"evidence\": \"Phf7 knockout transcriptomics with PPARα agonist (astaxanthin) rescue\",\n      \"pmids\": [\"37920670\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct mechanism of ERV suppression by PHF7 not defined\", \"PPARα-PHF7 link correlative\", \"Single study\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Associated Phf7 deficiency with reduced testicular steroidogenesis and downstream bone remodeling defects, hinting at an endocrine consequence of germline dysfunction.\",\n      \"evidence\": \"Phf7 knockout mice with hormone measurement, bone histomorphometry, and steroidogenesis marker RT-PCR\",\n      \"pmids\": [\"38430697\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No direct mechanistic link between PHF7 and steroidogenic gene regulation\", \"Correlative mRNA measurements only\", \"Bone phenotype likely secondary to hormone loss\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated PHF7 alone can reprogram fibroblasts to cardiomyocytes in vivo through genome-wide chromatin remodeling and upregulation of cardiac master regulators, consolidating its role as a single-factor reprogramming driver.\",\n      \"evidence\": \"Single-nucleus multiomics, in vitro transcriptomics, and in vivo retroviral delivery with fibroblast lineage tracing in infarcted mouse heart\",\n      \"pmids\": [\"40631661\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether E3 ligase activity is required for reprogramming untested\", \"Mechanism of chromatin remodeling beyond accessibility shifts unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PHF7's reader function, E3 ligase activity, and SWI/SNF cooperation are mechanistically integrated across the distinct germline and cardiac reprogramming contexts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether catalytic activity is required outside spermiogenesis is untested\", \"Full substrate repertoire beyond H2A and H3K14 is undefined\", \"No structure of PHF7 engaging both nucleosome and SWI/SNF\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4, 11]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"BRDT\", \"SWI/SNF\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}