{"gene":"GGNBP2","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2005,"finding":"GGNBP2 physically interacts with testicular germ cell-specific protein GGN1; yeast two-hybrid identified the interaction, and colocalization and co-immunoprecipitation in mammalian cells confirmed it. The interacting regions on both proteins were mapped.","method":"Yeast two-hybrid, colocalization, co-immunoprecipitation","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus yeast two-hybrid plus colocalization, single lab, multiple orthogonal methods","pmids":["15642376"],"is_preprint":false},{"year":2001,"finding":"GGNBP2 (DIF-3/ZFP403) protein localizes to the nucleus and possesses a zinc-finger motif at its N-terminus; it is highly expressed in the testes during spermatogenesis and is induced by TCDD (dioxin).","method":"Northern blot, protein detection, cDNA representational difference analysis","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — nuclear localization established by direct protein detection, replicated in testes context across multiple papers","pmids":["11728448"],"is_preprint":false},{"year":2016,"finding":"GGNBP2 protein physically interacts with estrogen receptor α (ERα) and functions as a nuclear receptor corepressor, inhibiting E2-induced activation of estrogen response element-driven transcription and attenuating ER target gene expression in breast cancer cells.","method":"Co-immunoprecipitation, estrogen response element reporter assay, overexpression and knockdown in T47D and MCF-7 cells, xenograft tumor growth assay","journal":"Breast cancer research and treatment","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, functional reporter assay, in vitro and in vivo experiments, multiple orthogonal methods in single study","pmids":["27357812"],"is_preprint":false},{"year":2016,"finding":"GGNBP2 loss in trophoblast stem cells (TSCs) aberrantly overactivates c-Met–Stat3 signaling, promoting TSC proliferation and delaying differentiation; Ggnbp2 null embryos die in utero with dysmorphic placentae.","method":"Ggnbp2 null mouse model, TSC knockdown and overexpression in vitro, western blot for c-Met phosphorylation and Stat3 activation","journal":"Biology of reproduction","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO phenotype plus in vitro knockdown/overexpression rescue, western blot pathway analysis, multiple orthogonal methods","pmids":["26764350"],"is_preprint":false},{"year":2017,"finding":"GGNBP2 is critically required for maintenance of adhesion integrity of the adlumenal germ epithelium during spermiogenesis; Ggnbp2-null male mice are sterile with azoospermia and dramatic spermatid morphological defects (irregular acrosomes, cytoplasmic remnant, ectopic manchette). Western blot showed increases in α-E-catenin, β-catenin, N-cadherin and decreases in E-cadherin, afadin, and nectin-3 in null testes.","method":"Ggnbp2 null mouse model (B6/129 background), histopathology, ultrastructural analysis, western blot for cell adhesion proteins","journal":"The American journal of pathology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with detailed ultrastructural and molecular phenotype, multiple adhesion molecule changes quantified, single rigorous study","pmids":["28823874"],"is_preprint":false},{"year":2017,"finding":"GGNBP2 knockout in mice causes absence of SOX9-positive Sertoli cells from seminiferous tubules and abnormal testis morphology, demonstrating a role in Sertoli cell maintenance during spermatogenesis.","method":"Heterozygous and homozygous GGNBP2 KO mouse model, SOX9 immunostaining, PCNA staining, apoptosis assays","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with specific cellular marker staining showing Sertoli cell loss, independent replication of male infertility phenotype across two KO studies","pmids":["28592902"],"is_preprint":false},{"year":2018,"finding":"GGNBP2 suppresses TNBC aggressiveness by inhibiting IL-6/STAT3 signaling activation; overexpression of GGNBP2 in MDA-MB-231 and Cal51 cells decreases activation of IL-6/STAT3 pathway, suppresses proliferation, migration, invasion, reduces cancer stem cell subpopulation, and inhibits tumor growth in vivo.","method":"Overexpression in TNBC cell lines, western blot for STAT3 pathway, in vitro functional assays (proliferation, migration, invasion), in vivo xenograft","journal":"Breast cancer research and treatment","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple in vitro and in vivo methods, single lab, pathway identification by western blot without direct binding evidence","pmids":["30450530"],"is_preprint":false},{"year":2018,"finding":"GGNBP2 co-immunoprecipitates with GGN1 in spermatocytes and has the same subcellular localization (spermatocyte, spermatid, spermatozoa). Ggnbp2 loss increases meiotic DNA double-strand breaks, compromises DSB repair, reduces crossovers, suppresses Ggn expression and nuclear accumulation. Overexpression of Ggnbp2 in Ggnbp2-null (but not Ggn-null) GC-2spd cells partially rescues haploid cell differentiation coinciding with restoration of Ggn expression, placing GGNBP2 upstream of GGN1 in the DSB repair pathway.","method":"Co-immunoprecipitation, immunofluorescence, flow cytometry, spread spermatocyte nuclei analysis, genetic rescue experiment in GC-2spd cells","journal":"Journal of cellular and molecular medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP for interaction, epistasis rescue experiment placing GGNBP2 upstream of GGN1, multiple orthogonal methods, single lab","pmids":["30055035"],"is_preprint":false},{"year":2022,"finding":"Fbxo45, a substrate recognition subunit of an E3 ubiquitin ligase, binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and proteasomal degradation, thereby destabilizing GGNBP2 and promoting ESCC tumorigenesis.","method":"Co-immunoprecipitation, ubiquitination assay, overexpression and knockdown in ESCC cell lines, in vivo xenograft, domain mapping","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding domain mapped, ubiquitination assay, in vitro and in vivo rescue experiments, multiple orthogonal methods in single rigorous study","pmids":["36127399"],"is_preprint":false},{"year":2024,"finding":"GGNBP2 acts between dsRNA transcription and cytoplasmic sensing by MDA5; GGNBP2 loss prevents induction of type I IFN and autoinflammation after ADAR1 editing loss by modifying the subcellular distribution of endogenous A-to-I editing substrates and reducing cytoplasmic dsRNA load. GGNBP2 interacts with CNOT10 and CNOT11 in this pathway.","method":"Genome-wide CRISPR screen, subcellular fractionation, dsRNA localization assay, IFN signaling assays, interaction studies","journal":"Science immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — unbiased genome-wide CRISPR screen followed by mechanistic characterization with subcellular fractionation, dsRNA load measurement, multiple orthogonal methods","pmids":["39576872"],"is_preprint":false},{"year":2024,"finding":"GGNBP2 regulates histone ubiquitination and methylation during spermatogenesis: it binds BRCC36 and RAD51 as a complex for DSB repair. GGNBP2 induces ASXL1 to activate the deubiquitinase BAP1 for H2A deubiquitination (H2AK119ubi); Ggnbp2 KO disrupts the ASXL1-BAP1 interaction and changes BAP1 localization. GGNBP2 KO also reduces H2B ubiquitination (H2BK120ubi) by affecting E2 enzyme and E3 ligase binding, and alters PRC2-mediated H3K27me3 and H3K79me2 levels.","method":"Co-immunoprecipitation, knockout in GC-2 cells and mouse testes, western blot for histone modifications, localization studies","journal":"Epigenetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for complex formation, histone modification western blots, single lab, multiple pathways examined but some mechanistic links inferred","pmids":["39109527"],"is_preprint":false},{"year":2016,"finding":"GGNBP2 overexpression suppresses PI3K/Akt and Wnt/β-catenin signaling in glioma cells; knockdown has the opposite effect. This was established by overexpression and knockdown with western blot readout of pathway components.","method":"Overexpression and knockdown in glioma cell lines, western blot for PI3K/Akt and Wnt/β-catenin pathway components","journal":"Oncology research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, functional overexpression/KD with western blot pathway readout, no direct binding evidence for pathway components","pmids":["28244851"],"is_preprint":false},{"year":2025,"finding":"miR-382-5p directly binds the GGNBP2 3'UTR to repress GGNBP2 expression; circ-0008536 acts as a competitive endogenous RNA by sequestering miR-382-5p, thereby derepressing GGNBP2 and restoring chemosensitivity in DOX-resistant TNBC cells.","method":"Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), miR-382-5p mimic intervention, GGNBP2 shRNA, xenograft","journal":"Translational oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dual-luciferase and RIP establish direct miR-382-5p/GGNBP2 3'UTR interaction, functional rescue confirms pathway, single lab","pmids":["40944974"],"is_preprint":false}],"current_model":"GGNBP2 is an evolutionarily conserved nuclear zinc-finger protein that functions as a tumor suppressor and spermatogenesis factor: it physically interacts with GGN1 to promote meiotic DSB repair (acting upstream of GGN1), interacts with ERα as a corepressor to inhibit estrogen signaling, inhibits IL-6/STAT3 and PI3K/Akt/Wnt signaling in cancer cells, is targeted for ubiquitination and proteasomal degradation by the E3 ligase subunit Fbxo45 (via its SPRY domain), regulates histone ubiquitination (H2A, H2B) and methylation (H3K27, H3K79) through ASXL1-BAP1 and related complexes during spermatogenesis, controls trophoblast stem cell proliferation/differentiation via suppression of c-Met–Stat3 signaling, and modulates cytoplasmic dsRNA load to regulate MDA5-mediated innate immune sensing downstream of ADAR1 editing."},"narrative":{"mechanistic_narrative":"GGNBP2 is an evolutionarily conserved nuclear zinc-finger protein that operates in two principal arenas: spermatogenesis and tumor suppression [PMID:11728448, PMID:28592902]. In the male germline it physically associates with the germ-cell-specific protein GGN1, and epistasis places GGNBP2 upstream of GGN1 to drive meiotic double-strand-break repair, support crossover formation, and enable haploid cell differentiation [PMID:15642376, PMID:30055035]. Genetic ablation in mice causes azoospermia with loss of SOX9-positive Sertoli cells, breakdown of adlumenal germ-epithelium adhesion, and severe spermatid defects [PMID:28823874, PMID:28592902], while in trophoblast stem cells GGNBP2 loss overactivates c-Met–Stat3 signaling and produces embryonic lethality with dysmorphic placentae [PMID:26764350]. Mechanistically, GGNBP2 shapes the germline chromatin landscape by organizing histone-modifying activities—nucleating an ASXL1–BAP1 axis for H2AK119 deubiquitination and influencing H2BK120 ubiquitination and PRC2-dependent H3K27/H3K79 methylation—and by partnering with BRCC36 and RAD51 in DSB repair [PMID:39109527]. In cancer, GGNBP2 acts as a suppressor by binding estrogen receptor α as a corepressor of estrogen-responsive transcription [PMID:27357812] and by restraining IL-6/STAT3, PI3K/Akt, and Wnt/β-catenin signaling [PMID:30450530, PMID:28244851]; its abundance is set by Fbxo45-mediated, SPRY-domain-dependent ubiquitination and proteasomal degradation and by miR-382-5p targeting of its 3'UTR [PMID:36127399, PMID:40944974]. Beyond these roles, GGNBP2 governs the subcellular distribution of A-to-I-edited endogenous substrates and cytoplasmic dsRNA load, positioning it between ADAR1 editing and MDA5-mediated innate immune sensing, where it associates with CNOT10 and CNOT11 [PMID:39576872].","teleology":[{"year":2001,"claim":"Established the basic identity of GGNBP2 as a nuclear zinc-finger protein expressed in testis, defining its candidate compartment and biological context.","evidence":"cDNA representational difference analysis, Northern blot, and protein detection of nuclear localization in testis induced by TCDD","pmids":["11728448"],"confidence":"Medium","gaps":["Zinc-finger DNA/protein-binding targets not defined","Functional role not yet tested"]},{"year":2005,"claim":"Identified GGN1 as the first physical partner of GGNBP2, anchoring it to germ-cell biology before its function was known.","evidence":"Yeast two-hybrid, colocalization, and reciprocal co-immunoprecipitation with interacting-region mapping in mammalian cells","pmids":["15642376"],"confidence":"Medium","gaps":["Functional consequence of the GGN1 interaction not established at this stage","Directionality of the GGNBP2–GGN1 relationship unknown"]},{"year":2016,"claim":"Defined GGNBP2 as a transcriptional corepressor of ERα, providing a molecular mechanism for tumor suppression in hormone-responsive breast cancer.","evidence":"Reciprocal Co-IP, estrogen response element reporter assays, knockdown/overexpression in T47D and MCF-7, and xenografts","pmids":["27357812"],"confidence":"High","gaps":["Whether corepression requires the zinc-finger or recruits additional chromatin machinery not resolved","Direct DNA occupancy not shown"]},{"year":2016,"claim":"Showed GGNBP2 restrains c-Met–Stat3 signaling to control trophoblast stem cell proliferation, revealing an essential developmental role beyond the germline.","evidence":"Ggnbp2-null mouse model with embryonic lethality, TSC knockdown/overexpression, and western blot for c-Met phosphorylation and Stat3 activation","pmids":["26764350"],"confidence":"High","gaps":["Direct molecular link between GGNBP2 and c-Met not defined","Whether nuclear corepressor activity underlies this effect unclear"]},{"year":2016,"claim":"Extended GGNBP2 tumor suppression to glioma by linking it to PI3K/Akt and Wnt/β-catenin pathway attenuation.","evidence":"Overexpression and knockdown in glioma cell lines with western blot pathway readouts","pmids":["28244851"],"confidence":"Medium","gaps":["No direct binding evidence for any pathway component","Mechanism connecting GGNBP2 to these kinases not identified"]},{"year":2017,"claim":"Genetic knockout established GGNBP2 as essential for spermatogenesis, causing Sertoli cell loss and breakdown of germ-epithelium adhesion integrity.","evidence":"Two independent Ggnbp2 KO mouse studies with SOX9 immunostaining, histopathology, ultrastructure, and western blot for adhesion proteins","pmids":["28592902","28823874"],"confidence":"High","gaps":["Whether adhesion and Sertoli phenotypes are cell-autonomous or secondary not resolved","Transcriptional vs structural mechanism of adhesion regulation unclear"]},{"year":2018,"claim":"Placed GGNBP2 upstream of GGN1 in meiotic DSB repair via an epistasis rescue, converting the earlier physical interaction into a defined pathway order.","evidence":"Co-IP, immunofluorescence, spread spermatocyte nuclei analysis, and genetic rescue in Ggnbp2-null versus Ggn-null GC-2spd cells","pmids":["30055035"],"confidence":"High","gaps":["Biochemical mechanism by which GGNBP2 promotes DSB repair not defined","How GGNBP2 controls Ggn expression unknown"]},{"year":2018,"claim":"Provided a signaling mechanism for GGNBP2 tumor suppression in triple-negative breast cancer through inhibition of IL-6/STAT3.","evidence":"Overexpression in MDA-MB-231 and Cal51, western blot for STAT3, functional assays, and xenografts","pmids":["30450530"],"confidence":"Medium","gaps":["No direct binding evidence to IL-6/STAT3 components","Single lab; mechanism of STAT3 suppression undefined"]},{"year":2022,"claim":"Identified Fbxo45 as the E3 ligase subunit that controls GGNBP2 abundance, explaining how its tumor-suppressor levels are post-translationally set.","evidence":"Co-IP, SPRY-domain mapping, ubiquitination assay, knockdown/overexpression in ESCC cells, and xenografts","pmids":["36127399"],"confidence":"High","gaps":["Signals regulating Fbxo45–GGNBP2 engagement not defined","Ubiquitination site on GGNBP2 not mapped"]},{"year":2024,"claim":"Revealed an unexpected innate-immunity role: GGNBP2 controls cytoplasmic dsRNA load and MDA5 sensing downstream of ADAR1 editing.","evidence":"Genome-wide CRISPR screen, subcellular fractionation, dsRNA localization, IFN assays, and interaction studies identifying CNOT10/CNOT11","pmids":["39576872"],"confidence":"High","gaps":["How GGNBP2 redistributes edited dsRNA substrates mechanistically unclear","Relationship of this role to its nuclear zinc-finger function unknown"]},{"year":2024,"claim":"Connected GGNBP2 to germline chromatin regulation by organizing histone ubiquitination and methylation through ASXL1-BAP1 and DSB-repair partners.","evidence":"Co-IP with BRCC36/RAD51 and ASXL1-BAP1, KO in GC-2 cells and testes, western blots for H2AK119ubi/H2BK120ubi/H3K27me3/H3K79me2, and localization studies","pmids":["39109527"],"confidence":"Medium","gaps":["Some mechanistic links inferred rather than directly shown","Whether GGNBP2 acts catalytically or as a scaffold not resolved"]},{"year":2025,"claim":"Defined an upstream non-coding RNA circuit (circ-0008536/miR-382-5p) that tunes GGNBP2 expression and chemosensitivity in resistant TNBC.","evidence":"Dual-luciferase reporter, RNA immunoprecipitation, miR-382-5p mimics, GGNBP2 shRNA, and xenografts","pmids":["40944974"],"confidence":"Medium","gaps":["Generality of this ceRNA axis beyond DOX-resistant TNBC unknown","Single lab"]},{"year":null,"claim":"It remains unresolved how GGNBP2's nuclear zinc-finger/corepressor activity, its cytoplasmic dsRNA-distribution role, and its germline chromatin functions are unified by a single biochemical activity.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct DNA/RNA target of the zinc finger defined","No structural model linking the molecular activities","Whether the cancer and germline roles share a common molecular mechanism unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[6,11,3]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[9]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[4,5,7]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,3,6,11]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[9]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[10]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[8]}],"complexes":["ASXL1-BAP1 complex","BRCC36-RAD51 DSB repair complex"],"partners":["GGN1","ESR1","FBXO45","ASXL1","BAP1","BRCC36","RAD51","CNOT10"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H3C7","full_name":"Gametogenetin-binding protein 2","aliases":["Laryngeal carcinoma-related protein 1","Protein ZNF403"],"length_aa":697,"mass_kda":79.1,"function":"May be involved in spermatogenesis","subcellular_location":"Cytoplasmic vesicle","url":"https://www.uniprot.org/uniprotkb/Q9H3C7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GGNBP2","classification":"Not Classified","n_dependent_lines":247,"n_total_lines":1208,"dependency_fraction":0.20447019867549668},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GGNBP2","total_profiled":1310},"omim":[{"mim_id":"620509","title":"CCR4-NOT TRANSCRIPTION COMPLEX, SUBUNIT 11; CNOT11","url":"https://www.omim.org/entry/620509"},{"mim_id":"620508","title":"CCR4-NOT TRANSCRIPTION COMPLEX, SUBUNIT 10; CNOT10","url":"https://www.omim.org/entry/620508"},{"mim_id":"612275","title":"GAMETOGENETIN-BINDING PROTEIN 2; GGNBP2","url":"https://www.omim.org/entry/612275"},{"mim_id":"609966","title":"GAMETOGENETIN; GGN","url":"https://www.omim.org/entry/609966"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GGNBP2"},"hgnc":{"alias_symbol":["ZFP403","LZK1","FLJ22561","FLJ21230","DIF-3","DIF3"],"prev_symbol":["ZNF403"]},"alphafold":{"accession":"Q9H3C7","domains":[{"cath_id":"-","chopping":"1-350","consensus_level":"medium","plddt":89.9723,"start":1,"end":350}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H3C7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H3C7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H3C7-F1-predicted_aligned_error_v6.png","plddt_mean":68.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GGNBP2","jax_strain_url":"https://www.jax.org/strain/search?query=GGNBP2"},"sequence":{"accession":"Q9H3C7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H3C7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H3C7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H3C7"}},"corpus_meta":[{"pmid":"3355503","id":"PMC_3355503","title":"Structure elucidation of two differentiation inducing factors (DIF-2 and DIF-3) from the cellular slime mould Dictyostelium discoideum.","date":"1988","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/3355503","citation_count":91,"is_preprint":false},{"pmid":"10528134","id":"PMC_10528134","title":"Effects of differentiation-inducing factors of Dictyostelium discoideum on human leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent.","date":"1999","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/10528134","citation_count":63,"is_preprint":false},{"pmid":"15642376","id":"PMC_15642376","title":"Yeast two-hybrid screens imply that GGNBP1, GGNBP2 and OAZ3 are potential interaction partners of testicular germ cell-specific protein GGN1.","date":"2005","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/15642376","citation_count":45,"is_preprint":false},{"pmid":"36127399","id":"PMC_36127399","title":"Fbxo45 promotes the malignant development of esophageal squamous cell carcinoma by targeting GGNBP2 for ubiquitination and degradation.","date":"2022","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/36127399","citation_count":31,"is_preprint":false},{"pmid":"11728448","id":"PMC_11728448","title":"Dioxin induces a novel nuclear factor, DIF-3, that is implicated in spermatogenesis.","date":"2001","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/11728448","citation_count":29,"is_preprint":false},{"pmid":"28592902","id":"PMC_28592902","title":"GGNBP2 is necessary for testis morphology and sperm development.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28592902","citation_count":19,"is_preprint":false},{"pmid":"27357812","id":"PMC_27357812","title":"GGNBP2 acts as a tumor suppressor by inhibiting estrogen receptor α activity in breast cancer cells.","date":"2016","source":"Breast cancer research and 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sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38395516","citation_count":2,"is_preprint":false},{"pmid":"39221224","id":"PMC_39221224","title":"HNF1β, LHX1, and GGNBP2 deletion contributed to kidney and reproductive dysfunction in 17q12 deletion syndrome: evidence from a case report.","date":"2024","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39221224","citation_count":2,"is_preprint":false},{"pmid":"40944974","id":"PMC_40944974","title":"Circ-0008536 inhibits doxorubicin resistance in triple-negative breast cancer via the miR-382-5p/GGNBP2 axis.","date":"2025","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40944974","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10466,"output_tokens":3481,"usd":0.041807,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10968,"output_tokens":4151,"usd":0.079308,"stage2_stop_reason":"end_turn"},"total_usd":0.121115,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"GGNBP2 physically interacts with testicular germ cell-specific protein GGN1; yeast two-hybrid identified the interaction, and colocalization and co-immunoprecipitation in mammalian cells confirmed it. The interacting regions on both proteins were mapped.\",\n      \"method\": \"Yeast two-hybrid, colocalization, co-immunoprecipitation\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus yeast two-hybrid plus colocalization, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"15642376\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"GGNBP2 (DIF-3/ZFP403) protein localizes to the nucleus and possesses a zinc-finger motif at its N-terminus; it is highly expressed in the testes during spermatogenesis and is induced by TCDD (dioxin).\",\n      \"method\": \"Northern blot, protein detection, cDNA representational difference analysis\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — nuclear localization established by direct protein detection, replicated in testes context across multiple papers\",\n      \"pmids\": [\"11728448\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"GGNBP2 protein physically interacts with estrogen receptor α (ERα) and functions as a nuclear receptor corepressor, inhibiting E2-induced activation of estrogen response element-driven transcription and attenuating ER target gene expression in breast cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, estrogen response element reporter assay, overexpression and knockdown in T47D and MCF-7 cells, xenograft tumor growth assay\",\n      \"journal\": \"Breast cancer research and treatment\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, functional reporter assay, in vitro and in vivo experiments, multiple orthogonal methods in single study\",\n      \"pmids\": [\"27357812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"GGNBP2 loss in trophoblast stem cells (TSCs) aberrantly overactivates c-Met–Stat3 signaling, promoting TSC proliferation and delaying differentiation; Ggnbp2 null embryos die in utero with dysmorphic placentae.\",\n      \"method\": \"Ggnbp2 null mouse model, TSC knockdown and overexpression in vitro, western blot for c-Met phosphorylation and Stat3 activation\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO phenotype plus in vitro knockdown/overexpression rescue, western blot pathway analysis, multiple orthogonal methods\",\n      \"pmids\": [\"26764350\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"GGNBP2 is critically required for maintenance of adhesion integrity of the adlumenal germ epithelium during spermiogenesis; Ggnbp2-null male mice are sterile with azoospermia and dramatic spermatid morphological defects (irregular acrosomes, cytoplasmic remnant, ectopic manchette). Western blot showed increases in α-E-catenin, β-catenin, N-cadherin and decreases in E-cadherin, afadin, and nectin-3 in null testes.\",\n      \"method\": \"Ggnbp2 null mouse model (B6/129 background), histopathology, ultrastructural analysis, western blot for cell adhesion proteins\",\n      \"journal\": \"The American journal of pathology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with detailed ultrastructural and molecular phenotype, multiple adhesion molecule changes quantified, single rigorous study\",\n      \"pmids\": [\"28823874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"GGNBP2 knockout in mice causes absence of SOX9-positive Sertoli cells from seminiferous tubules and abnormal testis morphology, demonstrating a role in Sertoli cell maintenance during spermatogenesis.\",\n      \"method\": \"Heterozygous and homozygous GGNBP2 KO mouse model, SOX9 immunostaining, PCNA staining, apoptosis assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with specific cellular marker staining showing Sertoli cell loss, independent replication of male infertility phenotype across two KO studies\",\n      \"pmids\": [\"28592902\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"GGNBP2 suppresses TNBC aggressiveness by inhibiting IL-6/STAT3 signaling activation; overexpression of GGNBP2 in MDA-MB-231 and Cal51 cells decreases activation of IL-6/STAT3 pathway, suppresses proliferation, migration, invasion, reduces cancer stem cell subpopulation, and inhibits tumor growth in vivo.\",\n      \"method\": \"Overexpression in TNBC cell lines, western blot for STAT3 pathway, in vitro functional assays (proliferation, migration, invasion), in vivo xenograft\",\n      \"journal\": \"Breast cancer research and treatment\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple in vitro and in vivo methods, single lab, pathway identification by western blot without direct binding evidence\",\n      \"pmids\": [\"30450530\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"GGNBP2 co-immunoprecipitates with GGN1 in spermatocytes and has the same subcellular localization (spermatocyte, spermatid, spermatozoa). Ggnbp2 loss increases meiotic DNA double-strand breaks, compromises DSB repair, reduces crossovers, suppresses Ggn expression and nuclear accumulation. Overexpression of Ggnbp2 in Ggnbp2-null (but not Ggn-null) GC-2spd cells partially rescues haploid cell differentiation coinciding with restoration of Ggn expression, placing GGNBP2 upstream of GGN1 in the DSB repair pathway.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, flow cytometry, spread spermatocyte nuclei analysis, genetic rescue experiment in GC-2spd cells\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP for interaction, epistasis rescue experiment placing GGNBP2 upstream of GGN1, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"30055035\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Fbxo45, a substrate recognition subunit of an E3 ubiquitin ligase, binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and proteasomal degradation, thereby destabilizing GGNBP2 and promoting ESCC tumorigenesis.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, overexpression and knockdown in ESCC cell lines, in vivo xenograft, domain mapping\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding domain mapped, ubiquitination assay, in vitro and in vivo rescue experiments, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"36127399\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GGNBP2 acts between dsRNA transcription and cytoplasmic sensing by MDA5; GGNBP2 loss prevents induction of type I IFN and autoinflammation after ADAR1 editing loss by modifying the subcellular distribution of endogenous A-to-I editing substrates and reducing cytoplasmic dsRNA load. GGNBP2 interacts with CNOT10 and CNOT11 in this pathway.\",\n      \"method\": \"Genome-wide CRISPR screen, subcellular fractionation, dsRNA localization assay, IFN signaling assays, interaction studies\",\n      \"journal\": \"Science immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — unbiased genome-wide CRISPR screen followed by mechanistic characterization with subcellular fractionation, dsRNA load measurement, multiple orthogonal methods\",\n      \"pmids\": [\"39576872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GGNBP2 regulates histone ubiquitination and methylation during spermatogenesis: it binds BRCC36 and RAD51 as a complex for DSB repair. GGNBP2 induces ASXL1 to activate the deubiquitinase BAP1 for H2A deubiquitination (H2AK119ubi); Ggnbp2 KO disrupts the ASXL1-BAP1 interaction and changes BAP1 localization. GGNBP2 KO also reduces H2B ubiquitination (H2BK120ubi) by affecting E2 enzyme and E3 ligase binding, and alters PRC2-mediated H3K27me3 and H3K79me2 levels.\",\n      \"method\": \"Co-immunoprecipitation, knockout in GC-2 cells and mouse testes, western blot for histone modifications, localization studies\",\n      \"journal\": \"Epigenetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for complex formation, histone modification western blots, single lab, multiple pathways examined but some mechanistic links inferred\",\n      \"pmids\": [\"39109527\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"GGNBP2 overexpression suppresses PI3K/Akt and Wnt/β-catenin signaling in glioma cells; knockdown has the opposite effect. This was established by overexpression and knockdown with western blot readout of pathway components.\",\n      \"method\": \"Overexpression and knockdown in glioma cell lines, western blot for PI3K/Akt and Wnt/β-catenin pathway components\",\n      \"journal\": \"Oncology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, functional overexpression/KD with western blot pathway readout, no direct binding evidence for pathway components\",\n      \"pmids\": [\"28244851\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"miR-382-5p directly binds the GGNBP2 3'UTR to repress GGNBP2 expression; circ-0008536 acts as a competitive endogenous RNA by sequestering miR-382-5p, thereby derepressing GGNBP2 and restoring chemosensitivity in DOX-resistant TNBC cells.\",\n      \"method\": \"Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), miR-382-5p mimic intervention, GGNBP2 shRNA, xenograft\",\n      \"journal\": \"Translational oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dual-luciferase and RIP establish direct miR-382-5p/GGNBP2 3'UTR interaction, functional rescue confirms pathway, single lab\",\n      \"pmids\": [\"40944974\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GGNBP2 is an evolutionarily conserved nuclear zinc-finger protein that functions as a tumor suppressor and spermatogenesis factor: it physically interacts with GGN1 to promote meiotic DSB repair (acting upstream of GGN1), interacts with ERα as a corepressor to inhibit estrogen signaling, inhibits IL-6/STAT3 and PI3K/Akt/Wnt signaling in cancer cells, is targeted for ubiquitination and proteasomal degradation by the E3 ligase subunit Fbxo45 (via its SPRY domain), regulates histone ubiquitination (H2A, H2B) and methylation (H3K27, H3K79) through ASXL1-BAP1 and related complexes during spermatogenesis, controls trophoblast stem cell proliferation/differentiation via suppression of c-Met–Stat3 signaling, and modulates cytoplasmic dsRNA load to regulate MDA5-mediated innate immune sensing downstream of ADAR1 editing.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GGNBP2 is an evolutionarily conserved nuclear zinc-finger protein that operates in two principal arenas: spermatogenesis and tumor suppression [#1, #5]. In the male germline it physically associates with the germ-cell-specific protein GGN1, and epistasis places GGNBP2 upstream of GGN1 to drive meiotic double-strand-break repair, support crossover formation, and enable haploid cell differentiation [#0, #7]. Genetic ablation in mice causes azoospermia with loss of SOX9-positive Sertoli cells, breakdown of adlumenal germ-epithelium adhesion, and severe spermatid defects [#4, #5], while in trophoblast stem cells GGNBP2 loss overactivates c-Met–Stat3 signaling and produces embryonic lethality with dysmorphic placentae [#3]. Mechanistically, GGNBP2 shapes the germline chromatin landscape by organizing histone-modifying activities—nucleating an ASXL1–BAP1 axis for H2AK119 deubiquitination and influencing H2BK120 ubiquitination and PRC2-dependent H3K27/H3K79 methylation—and by partnering with BRCC36 and RAD51 in DSB repair [#10]. In cancer, GGNBP2 acts as a suppressor by binding estrogen receptor α as a corepressor of estrogen-responsive transcription [#2] and by restraining IL-6/STAT3, PI3K/Akt, and Wnt/β-catenin signaling [#6, #11]; its abundance is set by Fbxo45-mediated, SPRY-domain-dependent ubiquitination and proteasomal degradation and by miR-382-5p targeting of its 3'UTR [#8, #12]. Beyond these roles, GGNBP2 governs the subcellular distribution of A-to-I-edited endogenous substrates and cytoplasmic dsRNA load, positioning it between ADAR1 editing and MDA5-mediated innate immune sensing, where it associates with CNOT10 and CNOT11 [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established the basic identity of GGNBP2 as a nuclear zinc-finger protein expressed in testis, defining its candidate compartment and biological context.\",\n      \"evidence\": \"cDNA representational difference analysis, Northern blot, and protein detection of nuclear localization in testis induced by TCDD\",\n      \"pmids\": [\"11728448\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Zinc-finger DNA/protein-binding targets not defined\", \"Functional role not yet tested\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified GGN1 as the first physical partner of GGNBP2, anchoring it to germ-cell biology before its function was known.\",\n      \"evidence\": \"Yeast two-hybrid, colocalization, and reciprocal co-immunoprecipitation with interacting-region mapping in mammalian cells\",\n      \"pmids\": [\"15642376\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the GGN1 interaction not established at this stage\", \"Directionality of the GGNBP2–GGN1 relationship unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined GGNBP2 as a transcriptional corepressor of ERα, providing a molecular mechanism for tumor suppression in hormone-responsive breast cancer.\",\n      \"evidence\": \"Reciprocal Co-IP, estrogen response element reporter assays, knockdown/overexpression in T47D and MCF-7, and xenografts\",\n      \"pmids\": [\"27357812\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether corepression requires the zinc-finger or recruits additional chromatin machinery not resolved\", \"Direct DNA occupancy not shown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed GGNBP2 restrains c-Met–Stat3 signaling to control trophoblast stem cell proliferation, revealing an essential developmental role beyond the germline.\",\n      \"evidence\": \"Ggnbp2-null mouse model with embryonic lethality, TSC knockdown/overexpression, and western blot for c-Met phosphorylation and Stat3 activation\",\n      \"pmids\": [\"26764350\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular link between GGNBP2 and c-Met not defined\", \"Whether nuclear corepressor activity underlies this effect unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extended GGNBP2 tumor suppression to glioma by linking it to PI3K/Akt and Wnt/β-catenin pathway attenuation.\",\n      \"evidence\": \"Overexpression and knockdown in glioma cell lines with western blot pathway readouts\",\n      \"pmids\": [\"28244851\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct binding evidence for any pathway component\", \"Mechanism connecting GGNBP2 to these kinases not identified\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Genetic knockout established GGNBP2 as essential for spermatogenesis, causing Sertoli cell loss and breakdown of germ-epithelium adhesion integrity.\",\n      \"evidence\": \"Two independent Ggnbp2 KO mouse studies with SOX9 immunostaining, histopathology, ultrastructure, and western blot for adhesion proteins\",\n      \"pmids\": [\"28592902\", \"28823874\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether adhesion and Sertoli phenotypes are cell-autonomous or secondary not resolved\", \"Transcriptional vs structural mechanism of adhesion regulation unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placed GGNBP2 upstream of GGN1 in meiotic DSB repair via an epistasis rescue, converting the earlier physical interaction into a defined pathway order.\",\n      \"evidence\": \"Co-IP, immunofluorescence, spread spermatocyte nuclei analysis, and genetic rescue in Ggnbp2-null versus Ggn-null GC-2spd cells\",\n      \"pmids\": [\"30055035\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Biochemical mechanism by which GGNBP2 promotes DSB repair not defined\", \"How GGNBP2 controls Ggn expression unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided a signaling mechanism for GGNBP2 tumor suppression in triple-negative breast cancer through inhibition of IL-6/STAT3.\",\n      \"evidence\": \"Overexpression in MDA-MB-231 and Cal51, western blot for STAT3, functional assays, and xenografts\",\n      \"pmids\": [\"30450530\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct binding evidence to IL-6/STAT3 components\", \"Single lab; mechanism of STAT3 suppression undefined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified Fbxo45 as the E3 ligase subunit that controls GGNBP2 abundance, explaining how its tumor-suppressor levels are post-translationally set.\",\n      \"evidence\": \"Co-IP, SPRY-domain mapping, ubiquitination assay, knockdown/overexpression in ESCC cells, and xenografts\",\n      \"pmids\": [\"36127399\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signals regulating Fbxo45–GGNBP2 engagement not defined\", \"Ubiquitination site on GGNBP2 not mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed an unexpected innate-immunity role: GGNBP2 controls cytoplasmic dsRNA load and MDA5 sensing downstream of ADAR1 editing.\",\n      \"evidence\": \"Genome-wide CRISPR screen, subcellular fractionation, dsRNA localization, IFN assays, and interaction studies identifying CNOT10/CNOT11\",\n      \"pmids\": [\"39576872\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How GGNBP2 redistributes edited dsRNA substrates mechanistically unclear\", \"Relationship of this role to its nuclear zinc-finger function unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected GGNBP2 to germline chromatin regulation by organizing histone ubiquitination and methylation through ASXL1-BAP1 and DSB-repair partners.\",\n      \"evidence\": \"Co-IP with BRCC36/RAD51 and ASXL1-BAP1, KO in GC-2 cells and testes, western blots for H2AK119ubi/H2BK120ubi/H3K27me3/H3K79me2, and localization studies\",\n      \"pmids\": [\"39109527\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Some mechanistic links inferred rather than directly shown\", \"Whether GGNBP2 acts catalytically or as a scaffold not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined an upstream non-coding RNA circuit (circ-0008536/miR-382-5p) that tunes GGNBP2 expression and chemosensitivity in resistant TNBC.\",\n      \"evidence\": \"Dual-luciferase reporter, RNA immunoprecipitation, miR-382-5p mimics, GGNBP2 shRNA, and xenografts\",\n      \"pmids\": [\"40944974\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Generality of this ceRNA axis beyond DOX-resistant TNBC unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how GGNBP2's nuclear zinc-finger/corepressor activity, its cytoplasmic dsRNA-distribution role, and its germline chromatin functions are unified by a single biochemical activity.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct DNA/RNA target of the zinc finger defined\", \"No structural model linking the molecular activities\", \"Whether the cancer and germline roles share a common molecular mechanism unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [6, 11, 3]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [4, 5, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 3, 6, 11]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"complexes\": [\n      \"ASXL1-BAP1 complex\",\n      \"BRCC36-RAD51 DSB repair complex\"\n    ],\n    \"partners\": [\n      \"GGN1\",\n      \"ESR1\",\n      \"FBXO45\",\n      \"ASXL1\",\n      \"BAP1\",\n      \"BRCC36\",\n      \"RAD51\",\n      \"CNOT10\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":6,"faith_total":6,"faith_pct":100.0}}