{"gene":"GATAD2B","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2006,"finding":"p66beta (GATAD2B) interacts physically and functionally with MBD2 within the Mi-2/NuRD complex; mutation of a conserved residue abolishes MBD2 binding and disrupts MBD2-mediated transcriptional repression. p66beta also binds histone tails of all octamer histones in vitro, and this interaction is abolished by acetylation of histone tails. The conserved region 2 (CR2) of p66beta is required for histone tail interaction and wild-type subnuclear distribution.","method":"In vitro binding assays (histone tail pull-down), site-directed mutagenesis, knockdown experiments, subnuclear localization by fluorescence microscopy","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro binding assays with mutagenesis plus functional repression assays and live-cell localization, single lab but multiple orthogonal methods","pmids":["16415179"],"is_preprint":false},{"year":2006,"finding":"p66alpha and p66beta function synergistically in the NuRD complex: knockdown of p66alpha impairs the repressive function of p66beta and vice versa, indicating cooperative activity within the complex.","method":"siRNA knockdown with transcriptional repression assays","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal knockdown with functional readout, single lab","pmids":["16415179"],"is_preprint":false},{"year":2014,"finding":"p66beta (GATAD2B) physically interacts with Suppressor of Fused (Sufu) and is recruited by Sufu to promoters of Hedgehog (Hh) target genes to block Gli-mediated transcriptional activation; p66beta negatively regulates Hh signaling downstream of Patched, Smoothened, and the primary cilium.","method":"Proteomic (mass spectrometry) identification of Sufu-interacting proteins, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), cell-based Hh signaling assays, zebrafish in vivo validation","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — proteomic identification confirmed by Co-IP and ChIP, plus zebrafish functional validation, multiple orthogonal methods in one study","pmids":["25403183"],"is_preprint":false},{"year":2014,"finding":"p66beta (GATAD2B) interacts with the catalytic domain of lysyl oxidase (LOX) through its CR2-containing domain, and co-expression of p66beta with LOX promotes nuclear accumulation of LOX in tumor cells.","method":"Yeast two-hybrid library screening, in vitro binding confirmation, co-expression localization in tumor cells","journal":"Cell and tissue research","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — yeast two-hybrid plus co-expression localization, single lab, limited mechanistic follow-up","pmids":["25118846"],"is_preprint":false},{"year":2018,"finding":"GATAD2B promotes both pro-tumorigenic and pro-metastatic activities in KRAS-mutant lung cancer through interaction with c-MYC and hyperactivation of the c-MYC pathway.","method":"In vivo functional screen in mouse KRAS-mutant lung adenocarcinoma model, regulatable mutant KRAS human cell model, lentiviral co-expression system, mechanistic evaluation of c-MYC pathway activity","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo screen plus mechanistic evaluation with two independent KRAS model systems, single lab","pmids":["30013058"],"is_preprint":false},{"year":2020,"finding":"Missense variants in the CR1 and CR2 conserved domains of GATAD2B disrupt its interactions with NuRD complex binding partners, establishing these domains as critical for NuRD complex assembly.","method":"Immunoprecipitation assays using in vitro transcription-translation products of wild-type and mutant GATAD2B","journal":"Genetics in medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay with multiple disease-associated mutants tested, single lab","pmids":["31949314"],"is_preprint":false},{"year":2021,"finding":"MAP2K6 (MKK6) phosphorylates GATAD2B, and this phosphorylation is required for MKK6-mediated heterochromatin loosening and elevated histone acetylation levels during somatic cell reprogramming; this activity does not depend on the canonical MKK6 target P38.","method":"Kinase phosphorylation assays identifying GATAD2B as MKK6 substrate, genetic epistasis (kinase-dead MKK6 mutant), ChIP for Sox2/Klf4 binding, histone acetylation assays","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — kinase substrate identification with functional epistasis and chromatin readout, single lab","pmids":["34815549"],"is_preprint":false},{"year":2023,"finding":"p66beta (GATAD2B) acts as a co-activator of the transcription factor Snail in breast cancer cells: Snail interacts with p66beta, and p66beta enhances Snail binding affinity to G-box (5'-GGGAGG-3') cis-elements in promoters of migration-promoting genes, thereby inducing their transcription and promoting cell migration and lung metastasis.","method":"Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), gene knockdown, luciferase reporter assays, in vivo metastasis assay in BALB/c mice","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, ChIP, reporter assays, and in vivo validation, single lab with multiple orthogonal methods","pmids":["37380643"],"is_preprint":false},{"year":2024,"finding":"The GATAD2B-NuRD complex is recruited to DNA double-strand breaks (DSBs) in a transcription- and DNA:RNA hybrid (R-loop)-dependent manner, promotes histone deacetylation and chromatin condensation at DSBs, establishes a spatial boundary between open and closed chromatin, and is required for correct termination of DNA end resection; loss of GATAD2B-NuRD leads to chromatin hyperrelaxation, extended DNA end resection, and homologous recombination repair failure.","method":"ChIP, DNA damage assays, R-loop detection, chromatin fractionation, end resection assays, HR repair assays, genetic loss-of-function experiments","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (ChIP, chromatin fractionation, end resection, HR assays) establishing mechanistic pathway, single lab rigorous study","pmids":["38719994"],"is_preprint":false},{"year":2024,"finding":"GATAD2B shows specific nuclear localization from the late 2-cell stage to the 8-cell stage in mouse embryos; depletion of GATAD2B impairs zygotic genome activation (ZGA), inhibits cell cycle G2/M phase transition, increases DNA damage at the morula stage, and reduces blastocyst formation, indicating GATAD2B is required for pre-implantation embryonic development.","method":"Immunofluorescence localization, siRNA knockdown, transcriptome analysis, proteomic analysis, live-embryo imaging, MERVL expression as ZGA marker","journal":"Cell proliferation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined transcriptomic and developmental phenotype plus localization, single lab with multiple readouts","pmids":["38605678"],"is_preprint":false},{"year":2025,"finding":"GATAD2B is O-GlcNAcylated by OGT at its C-terminus; this modification protects GATAD2B from ubiquitination and proteasomal degradation. ITCH was identified as a novel E3 ubiquitin ligase for GATAD2B. O-GlcNAcylation-dependent stabilization of GATAD2B promotes breast cancer stem-like cell (CSC) maintenance, mammosphere formation, and drug resistance.","method":"Proteomics/O-GlcNAcome analysis identifying GATAD2B as OGT substrate, site-directed mutagenesis of O-GlcNAc sites, ubiquitination assays, genetic knockdown/overexpression, mammosphere formation assays","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — substrate identification by proteomics confirmed by mutagenesis and functional assays, E3 ligase identification, single lab with multiple orthogonal methods","pmids":["40136647"],"is_preprint":false},{"year":2025,"finding":"GATAD2B regulates spindle assembly during oocyte meiosis: GATAD2B protein is stably expressed during oocyte meiosis with increased levels at MII; knockdown causes abnormal spindle assembly, chromosome misalignment, MI block, abnormal microtubule organizing center distribution, and aneuploidy, associated with downregulation of deacetylation-related genes and abnormal accumulation of acetylated proteins.","method":"Western blot, immunofluorescence, siRNA microinjection knockdown, live-cell imaging, spindle/DNA staining, RNA-seq reanalysis","journal":"Animal bioscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined meiotic phenotype and mechanistic link to histone deacetylation, single lab with multiple orthogonal methods","pmids":["40468728"],"is_preprint":false}],"current_model":"GATAD2B (p66beta) is a core subunit of the NuRD chromatin remodeling/histone deacetylase complex that binds MBD2 and unmodified histone tails via its CR2 domain to mediate transcriptional repression at methylated chromatin; it is recruited by Sufu to repress Hedgehog target genes in the nucleus; it is phosphorylated by MAP2K6 to regulate heterochromatin loosening; it is O-GlcNAcylated at its C-terminus by OGT (with ITCH as its E3 ubiquitin ligase), stabilizing it and promoting cancer stem-cell maintenance; it acts as a co-activator of Snail at G-box promoter elements to drive cell migration; it is recruited to DNA double-strand breaks in an R-loop-dependent manner to promote histone deacetylation and establish chromatin boundaries required for proper HR repair; and it is required for zygotic genome activation and meiotic spindle assembly during early development."},"narrative":{"mechanistic_narrative":"GATAD2B (p66beta) is a core subunit of the Mi-2/NuRD chromatin remodeling and histone deacetylase complex that mediates transcriptional repression at chromatin: it binds MBD2 within NuRD and engages the tails of all octamer histones in vitro through its conserved region 2 (CR2), an interaction abolished by histone tail acetylation, while a conserved-residue mutation disrupts MBD2-dependent repression and proper subnuclear distribution [PMID:16415179]. Its CR1 and CR2 domains are required for assembly into NuRD, and disease-associated missense variants in these domains disrupt binding to NuRD partners [PMID:31949314]; p66beta and its paralog p66alpha act cooperatively to enforce repression [PMID:16415179]. Beyond constitutive repression, GATAD2B is recruited to Hedgehog target gene promoters by Suppressor of Fused to block Gli-mediated activation downstream of the primary cilium [PMID:25403183], and the GATAD2B-NuRD complex is recruited to DNA double-strand breaks in a transcription- and R-loop-dependent manner, where it drives histone deacetylation and chromatin condensation to establish a boundary that terminates DNA end resection and enables homologous recombination repair [PMID:38719994]. GATAD2B is required in early development for zygotic genome activation, the G2/M transition, and genome integrity during pre-implantation embryogenesis [PMID:38605678], and for spindle assembly and chromosome alignment during oocyte meiosis, where its loss causes accumulation of acetylated proteins and aneuploidy [PMID:40468728]. GATAD2B activity is tuned by post-translational modification—phosphorylation by MAP2K6 promotes heterochromatin loosening independent of p38 [PMID:34815549], and O-GlcNAcylation by OGT at its C-terminus protects it from ITCH-mediated ubiquitination and degradation [PMID:40136647]. In cancer it acts beyond canonical repression, serving as a co-activator of Snail at G-box promoter elements to drive migration and metastasis [PMID:37380643] and supporting KRAS-mutant tumorigenesis through c-MYC pathway hyperactivation [PMID:30013058].","teleology":[{"year":2006,"claim":"Established GATAD2B as a histone- and MBD2-binding subunit of NuRD that reads unmodified histone tails to mediate repression, defining its core molecular function.","evidence":"In vitro histone tail pull-downs, site-directed mutagenesis, knockdown repression assays, and subnuclear localization in cells","pmids":["16415179"],"confidence":"High","gaps":["Structural basis of CR2-histone tail recognition not resolved","In vitro histone binding not shown at native chromatin","Genome-wide repression targets not mapped"]},{"year":2006,"claim":"Showed p66alpha and p66beta act cooperatively within NuRD, indicating functional interdependence of paralogous subunits rather than redundancy.","evidence":"Reciprocal siRNA knockdown with transcriptional repression readouts","pmids":["16415179"],"confidence":"Medium","gaps":["Single-lab functional assay without biochemical reconstitution","Quantitative stoichiometry of p66alpha/p66beta in NuRD unknown"]},{"year":2014,"claim":"Connected GATAD2B to developmental signaling by showing Sufu recruits it to Hedgehog target promoters to repress Gli activation, placing NuRD repression downstream of cilium-dependent Hh signaling.","evidence":"Mass spectrometry, Co-IP, ChIP, cell-based Hh assays, and zebrafish validation","pmids":["25403183"],"confidence":"High","gaps":["Whether full NuRD complex is recruited with GATAD2B at Hh genes not defined","Direct Sufu-binding interface on GATAD2B unmapped"]},{"year":2014,"claim":"Identified a LOX interaction via the CR2-containing domain promoting nuclear LOX accumulation, hinting at a non-canonical chaperone/localization role.","evidence":"Yeast two-hybrid screen, in vitro binding, and co-expression localization in tumor cells","pmids":["25118846"],"confidence":"Medium","gaps":["Y2H plus co-localization without functional consequence established","No endogenous interaction or mechanism validated"]},{"year":2018,"claim":"Linked GATAD2B to oncogenic signaling by showing it drives KRAS-mutant lung cancer through c-MYC pathway hyperactivation, broadening its role beyond chromatin repression.","evidence":"In vivo functional screen, regulatable KRAS cell models, and c-MYC pathway evaluation","pmids":["30013058"],"confidence":"Medium","gaps":["Molecular basis of GATAD2B-c-MYC interaction not detailed","Whether effect requires NuRD unknown"]},{"year":2020,"claim":"Defined CR1 and CR2 as the domains required for NuRD assembly by showing disease-associated missense variants disrupt partner binding, providing a molecular basis for GATAD2B-related pathology.","evidence":"Immunoprecipitation of in vitro-translated wild-type and mutant GATAD2B","pmids":["31949314"],"confidence":"Medium","gaps":["Cellular and developmental consequences of variants not tested here","Which specific NuRD subunits each domain contacts not resolved"]},{"year":2021,"claim":"Revealed phosphoregulation of GATAD2B by MAP2K6 driving heterochromatin loosening during reprogramming, independent of canonical p38 signaling.","evidence":"Kinase substrate assays, kinase-dead epistasis, ChIP, and histone acetylation assays","pmids":["34815549"],"confidence":"Medium","gaps":["Phosphosites on GATAD2B not pinpointed","Mechanism linking phosphorylation to reduced repression unclear"]},{"year":2023,"claim":"Showed GATAD2B can act as a transcriptional co-activator, enhancing Snail binding to G-box elements to promote migration genes, reversing its expected repressive role in a context-specific manner.","evidence":"Reciprocal Co-IP, ChIP, luciferase reporters, knockdown, and in vivo mouse metastasis","pmids":["37380643"],"confidence":"Medium","gaps":["How a NuRD subunit switches to co-activation not mechanistically explained","Whether NuRD complex participates unknown"]},{"year":2024,"claim":"Established GATAD2B-NuRD as an R-loop-dependent responder at DNA double-strand breaks that condenses chromatin to bound DNA end resection and enable HR repair, defining a genome-stability function.","evidence":"ChIP, R-loop detection, chromatin fractionation, end resection and HR assays, and loss-of-function","pmids":["38719994"],"confidence":"High","gaps":["Recruitment factor reading R-loops not identified","Connection to GATAD2B histone-binding CR2 not directly tested"]},{"year":2024,"claim":"Demonstrated GATAD2B is required for zygotic genome activation and pre-implantation development, extending its chromatin role into embryonic genome reprogramming.","evidence":"Immunofluorescence, siRNA knockdown, transcriptomics, proteomics, and live embryo imaging in mouse","pmids":["38605678"],"confidence":"Medium","gaps":["Direct target genes at ZGA not defined","Whether DNA damage phenotype reflects the HR role unclear"]},{"year":2025,"claim":"Identified O-GlcNAcylation by OGT and ITCH-mediated ubiquitination as opposing modifications controlling GATAD2B stability, linking its abundance to cancer stem-cell maintenance.","evidence":"O-GlcNAcome proteomics, site mutagenesis, ubiquitination assays, and mammosphere assays","pmids":["40136647"],"confidence":"Medium","gaps":["Specific O-GlcNAc and ubiquitination residues' interplay not fully mapped","Whether stabilization alters NuRD function not tested"]},{"year":2025,"claim":"Showed GATAD2B controls meiotic spindle assembly and chromosome alignment in oocytes via deacetylation-related gene regulation, connecting its repressive function to faithful chromosome segregation.","evidence":"Western blot, immunofluorescence, siRNA microinjection, live imaging, and RNA-seq reanalysis","pmids":["40468728"],"confidence":"Medium","gaps":["Direct spindle-associated mechanism vs transcriptional effect not separated","Targets driving acetylated-protein accumulation not identified"]},{"year":null,"claim":"How GATAD2B's single biochemical identity as a NuRD histone-reader is reconciled with its context-specific co-activator role and its non-chromatin functions (LOX, c-MYC) remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of GATAD2B within NuRD","No unified mechanism explaining repressor-to-activator switching","Whether developmental and DNA-repair roles share the same complex composition unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,2,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,5]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,9]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0,8]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,8]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[8]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,2,7]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2]}],"complexes":["Mi-2/NuRD complex"],"partners":["MBD2","GATAD2A","SUFU","MAP2K6","OGT","ITCH","SNAI1","MYC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WXI9","full_name":"Transcriptional repressor p66-beta","aliases":["GATA zinc finger domain-containing protein 2B","p66/p68"],"length_aa":593,"mass_kda":65.3,"function":"Transcriptional repressor (PubMed:12183469, PubMed:16415179). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, PubMed:16415179). Efficient repression requires the presence of GATAD2A (PubMed:16415179). Targets MBD3 to discrete loci in the nucleus (PubMed:11756549). May play a role in synapse development (PubMed:23644463)","subcellular_location":"Nucleus speckle; Nucleus; Chromosome","url":"https://www.uniprot.org/uniprotkb/Q8WXI9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GATAD2B","classification":"Not Classified","n_dependent_lines":38,"n_total_lines":1208,"dependency_fraction":0.03145695364238411},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HDAC1","stoichiometry":10.0},{"gene":"HDAC2","stoichiometry":10.0},{"gene":"ACTG1","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"CTBP2","stoichiometry":0.2},{"gene":"EMC9","stoichiometry":0.2},{"gene":"H2AFZ","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"KPNA4","stoichiometry":0.2},{"gene":"RBBP4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/GATAD2B","total_profiled":1310},"omim":[{"mim_id":"620896","title":"LEUCINE-RICH REPEAT-CONTAINING PROTEIN 42; LRRC42","url":"https://www.omim.org/entry/620896"},{"mim_id":"615074","title":"GAND SYNDROME; GAND","url":"https://www.omim.org/entry/615074"},{"mim_id":"614998","title":"GATA ZINC FINGER DOMAIN-CONTAINING PROTEIN 2B; GATAD2B","url":"https://www.omim.org/entry/614998"},{"mim_id":"614997","title":"GATA ZINC FINGER DOMAIN-CONTAINING PROTEIN 2A; GATAD2A","url":"https://www.omim.org/entry/614997"},{"mim_id":"603573","title":"METHYL-CpG-BINDING DOMAIN PROTEIN 3; MBD3","url":"https://www.omim.org/entry/603573"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GATAD2B"},"hgnc":{"alias_symbol":["P66beta"],"prev_symbol":[]},"alphafold":{"accession":"Q8WXI9","domains":[{"cath_id":"3.30.50","chopping":"417-481","consensus_level":"medium","plddt":89.1303,"start":417,"end":481}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WXI9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WXI9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WXI9-F1-predicted_aligned_error_v6.png","plddt_mean":58.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GATAD2B","jax_strain_url":"https://www.jax.org/strain/search?query=GATAD2B"},"sequence":{"accession":"Q8WXI9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WXI9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WXI9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WXI9"}},"corpus_meta":[{"pmid":"16415179","id":"PMC_16415179","title":"p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction.","date":"2006","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/16415179","citation_count":67,"is_preprint":false},{"pmid":"23644463","id":"PMC_23644463","title":"GATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila.","date":"2013","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23644463","citation_count":58,"is_preprint":false},{"pmid":"30013058","id":"PMC_30013058","title":"In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30013058","citation_count":42,"is_preprint":false},{"pmid":"25403183","id":"PMC_25403183","title":"Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling.","date":"2014","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/25403183","citation_count":39,"is_preprint":false},{"pmid":"31949314","id":"PMC_31949314","title":"GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder.","date":"2020","source":"Genetics in medicine : official journal of the American College of Medical Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31949314","citation_count":23,"is_preprint":false},{"pmid":"25118846","id":"PMC_25118846","title":"Nuclear translocation of lysyl oxidase is promoted by interaction with transcription repressor p66β.","date":"2014","source":"Cell and tissue research","url":"https://pubmed.ncbi.nlm.nih.gov/25118846","citation_count":15,"is_preprint":false},{"pmid":"28077840","id":"PMC_28077840","title":"Novel GATAD2B loss-of-function mutations cause intellectual disability in two unrelated cases.","date":"2017","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28077840","citation_count":15,"is_preprint":false},{"pmid":"28211977","id":"PMC_28211977","title":"1q21.3 deletion involving GATAD2B: An emerging recurrent microdeletion syndrome.","date":"2017","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/28211977","citation_count":13,"is_preprint":false},{"pmid":"30482549","id":"PMC_30482549","title":"A novel mutation in the GATAD2B gene associated with severe intellectual disability.","date":"2018","source":"Brain & development","url":"https://pubmed.ncbi.nlm.nih.gov/30482549","citation_count":13,"is_preprint":false},{"pmid":"32688057","id":"PMC_32688057","title":"Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND).","date":"2020","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32688057","citation_count":12,"is_preprint":false},{"pmid":"38719994","id":"PMC_38719994","title":"The GATAD2B-NuRD complex drives DNA:RNA hybrid-dependent chromatin boundary formation upon DNA damage.","date":"2024","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/38719994","citation_count":11,"is_preprint":false},{"pmid":"34815549","id":"PMC_34815549","title":"MAP2K6 remodels chromatin and facilitates reprogramming by activating Gatad2b-phosphorylation dependent heterochromatin loosening.","date":"2021","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/34815549","citation_count":11,"is_preprint":false},{"pmid":"30346093","id":"PMC_30346093","title":"Intellectual disability due to monoallelic variant in GATAD2B and mosaicism in unaffected parent.","date":"2018","source":"American journal of medical genetics. 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Part A","url":"https://pubmed.ncbi.nlm.nih.gov/40770973","citation_count":1,"is_preprint":false},{"pmid":"40468728","id":"PMC_40468728","title":"GATAD2B regulates spindle assembly by affecting protein deacetylation during oocyte meiotic maturation.","date":"2025","source":"Animal bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/40468728","citation_count":0,"is_preprint":false},{"pmid":"37818386","id":"PMC_37818386","title":"Uterine tumor resembling high-grade endometrial mesenchymal sarcoma with GATAD2B-MMRN1 fusion.","date":"2023","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/37818386","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15413,"output_tokens":3114,"usd":0.046475,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10517,"output_tokens":3976,"usd":0.075993,"stage2_stop_reason":"end_turn"},"total_usd":0.122468,"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\": 2006,\n      \"finding\": \"p66beta (GATAD2B) interacts physically and functionally with MBD2 within the Mi-2/NuRD complex; mutation of a conserved residue abolishes MBD2 binding and disrupts MBD2-mediated transcriptional repression. p66beta also binds histone tails of all octamer histones in vitro, and this interaction is abolished by acetylation of histone tails. The conserved region 2 (CR2) of p66beta is required for histone tail interaction and wild-type subnuclear distribution.\",\n      \"method\": \"In vitro binding assays (histone tail pull-down), site-directed mutagenesis, knockdown experiments, subnuclear localization by fluorescence microscopy\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro binding assays with mutagenesis plus functional repression assays and live-cell localization, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"16415179\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"p66alpha and p66beta function synergistically in the NuRD complex: knockdown of p66alpha impairs the repressive function of p66beta and vice versa, indicating cooperative activity within the complex.\",\n      \"method\": \"siRNA knockdown with transcriptional repression assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal knockdown with functional readout, single lab\",\n      \"pmids\": [\"16415179\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"p66beta (GATAD2B) physically interacts with Suppressor of Fused (Sufu) and is recruited by Sufu to promoters of Hedgehog (Hh) target genes to block Gli-mediated transcriptional activation; p66beta negatively regulates Hh signaling downstream of Patched, Smoothened, and the primary cilium.\",\n      \"method\": \"Proteomic (mass spectrometry) identification of Sufu-interacting proteins, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), cell-based Hh signaling assays, zebrafish in vivo validation\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — proteomic identification confirmed by Co-IP and ChIP, plus zebrafish functional validation, multiple orthogonal methods in one study\",\n      \"pmids\": [\"25403183\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"p66beta (GATAD2B) interacts with the catalytic domain of lysyl oxidase (LOX) through its CR2-containing domain, and co-expression of p66beta with LOX promotes nuclear accumulation of LOX in tumor cells.\",\n      \"method\": \"Yeast two-hybrid library screening, in vitro binding confirmation, co-expression localization in tumor cells\",\n      \"journal\": \"Cell and tissue research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — yeast two-hybrid plus co-expression localization, single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"25118846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"GATAD2B promotes both pro-tumorigenic and pro-metastatic activities in KRAS-mutant lung cancer through interaction with c-MYC and hyperactivation of the c-MYC pathway.\",\n      \"method\": \"In vivo functional screen in mouse KRAS-mutant lung adenocarcinoma model, regulatable mutant KRAS human cell model, lentiviral co-expression system, mechanistic evaluation of c-MYC pathway activity\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo screen plus mechanistic evaluation with two independent KRAS model systems, single lab\",\n      \"pmids\": [\"30013058\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Missense variants in the CR1 and CR2 conserved domains of GATAD2B disrupt its interactions with NuRD complex binding partners, establishing these domains as critical for NuRD complex assembly.\",\n      \"method\": \"Immunoprecipitation assays using in vitro transcription-translation products of wild-type and mutant GATAD2B\",\n      \"journal\": \"Genetics in medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay with multiple disease-associated mutants tested, single lab\",\n      \"pmids\": [\"31949314\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MAP2K6 (MKK6) phosphorylates GATAD2B, and this phosphorylation is required for MKK6-mediated heterochromatin loosening and elevated histone acetylation levels during somatic cell reprogramming; this activity does not depend on the canonical MKK6 target P38.\",\n      \"method\": \"Kinase phosphorylation assays identifying GATAD2B as MKK6 substrate, genetic epistasis (kinase-dead MKK6 mutant), ChIP for Sox2/Klf4 binding, histone acetylation assays\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — kinase substrate identification with functional epistasis and chromatin readout, single lab\",\n      \"pmids\": [\"34815549\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"p66beta (GATAD2B) acts as a co-activator of the transcription factor Snail in breast cancer cells: Snail interacts with p66beta, and p66beta enhances Snail binding affinity to G-box (5'-GGGAGG-3') cis-elements in promoters of migration-promoting genes, thereby inducing their transcription and promoting cell migration and lung metastasis.\",\n      \"method\": \"Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), gene knockdown, luciferase reporter assays, in vivo metastasis assay in BALB/c mice\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, ChIP, reporter assays, and in vivo validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"37380643\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The GATAD2B-NuRD complex is recruited to DNA double-strand breaks (DSBs) in a transcription- and DNA:RNA hybrid (R-loop)-dependent manner, promotes histone deacetylation and chromatin condensation at DSBs, establishes a spatial boundary between open and closed chromatin, and is required for correct termination of DNA end resection; loss of GATAD2B-NuRD leads to chromatin hyperrelaxation, extended DNA end resection, and homologous recombination repair failure.\",\n      \"method\": \"ChIP, DNA damage assays, R-loop detection, chromatin fractionation, end resection assays, HR repair assays, genetic loss-of-function experiments\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (ChIP, chromatin fractionation, end resection, HR assays) establishing mechanistic pathway, single lab rigorous study\",\n      \"pmids\": [\"38719994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GATAD2B shows specific nuclear localization from the late 2-cell stage to the 8-cell stage in mouse embryos; depletion of GATAD2B impairs zygotic genome activation (ZGA), inhibits cell cycle G2/M phase transition, increases DNA damage at the morula stage, and reduces blastocyst formation, indicating GATAD2B is required for pre-implantation embryonic development.\",\n      \"method\": \"Immunofluorescence localization, siRNA knockdown, transcriptome analysis, proteomic analysis, live-embryo imaging, MERVL expression as ZGA marker\",\n      \"journal\": \"Cell proliferation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined transcriptomic and developmental phenotype plus localization, single lab with multiple readouts\",\n      \"pmids\": [\"38605678\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GATAD2B is O-GlcNAcylated by OGT at its C-terminus; this modification protects GATAD2B from ubiquitination and proteasomal degradation. ITCH was identified as a novel E3 ubiquitin ligase for GATAD2B. O-GlcNAcylation-dependent stabilization of GATAD2B promotes breast cancer stem-like cell (CSC) maintenance, mammosphere formation, and drug resistance.\",\n      \"method\": \"Proteomics/O-GlcNAcome analysis identifying GATAD2B as OGT substrate, site-directed mutagenesis of O-GlcNAc sites, ubiquitination assays, genetic knockdown/overexpression, mammosphere formation assays\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — substrate identification by proteomics confirmed by mutagenesis and functional assays, E3 ligase identification, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"40136647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GATAD2B regulates spindle assembly during oocyte meiosis: GATAD2B protein is stably expressed during oocyte meiosis with increased levels at MII; knockdown causes abnormal spindle assembly, chromosome misalignment, MI block, abnormal microtubule organizing center distribution, and aneuploidy, associated with downregulation of deacetylation-related genes and abnormal accumulation of acetylated proteins.\",\n      \"method\": \"Western blot, immunofluorescence, siRNA microinjection knockdown, live-cell imaging, spindle/DNA staining, RNA-seq reanalysis\",\n      \"journal\": \"Animal bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined meiotic phenotype and mechanistic link to histone deacetylation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"40468728\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GATAD2B (p66beta) is a core subunit of the NuRD chromatin remodeling/histone deacetylase complex that binds MBD2 and unmodified histone tails via its CR2 domain to mediate transcriptional repression at methylated chromatin; it is recruited by Sufu to repress Hedgehog target genes in the nucleus; it is phosphorylated by MAP2K6 to regulate heterochromatin loosening; it is O-GlcNAcylated at its C-terminus by OGT (with ITCH as its E3 ubiquitin ligase), stabilizing it and promoting cancer stem-cell maintenance; it acts as a co-activator of Snail at G-box promoter elements to drive cell migration; it is recruited to DNA double-strand breaks in an R-loop-dependent manner to promote histone deacetylation and establish chromatin boundaries required for proper HR repair; and it is required for zygotic genome activation and meiotic spindle assembly during early development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GATAD2B (p66beta) is a core subunit of the Mi-2/NuRD chromatin remodeling and histone deacetylase complex that mediates transcriptional repression at chromatin: it binds MBD2 within NuRD and engages the tails of all octamer histones in vitro through its conserved region 2 (CR2), an interaction abolished by histone tail acetylation, while a conserved-residue mutation disrupts MBD2-dependent repression and proper subnuclear distribution [#0]. Its CR1 and CR2 domains are required for assembly into NuRD, and disease-associated missense variants in these domains disrupt binding to NuRD partners [#5]; p66beta and its paralog p66alpha act cooperatively to enforce repression [#1]. Beyond constitutive repression, GATAD2B is recruited to Hedgehog target gene promoters by Suppressor of Fused to block Gli-mediated activation downstream of the primary cilium [#2], and the GATAD2B-NuRD complex is recruited to DNA double-strand breaks in a transcription- and R-loop-dependent manner, where it drives histone deacetylation and chromatin condensation to establish a boundary that terminates DNA end resection and enables homologous recombination repair [#8]. GATAD2B is required in early development for zygotic genome activation, the G2/M transition, and genome integrity during pre-implantation embryogenesis [#9], and for spindle assembly and chromosome alignment during oocyte meiosis, where its loss causes accumulation of acetylated proteins and aneuploidy [#11]. GATAD2B activity is tuned by post-translational modification\\u2014phosphorylation by MAP2K6 promotes heterochromatin loosening independent of p38 [#6], and O-GlcNAcylation by OGT at its C-terminus protects it from ITCH-mediated ubiquitination and degradation [#10]. In cancer it acts beyond canonical repression, serving as a co-activator of Snail at G-box promoter elements to drive migration and metastasis [#7] and supporting KRAS-mutant tumorigenesis through c-MYC pathway hyperactivation [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established GATAD2B as a histone- and MBD2-binding subunit of NuRD that reads unmodified histone tails to mediate repression, defining its core molecular function.\",\n      \"evidence\": \"In vitro histone tail pull-downs, site-directed mutagenesis, knockdown repression assays, and subnuclear localization in cells\",\n      \"pmids\": [\"16415179\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of CR2-histone tail recognition not resolved\", \"In vitro histone binding not shown at native chromatin\", \"Genome-wide repression targets not mapped\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Showed p66alpha and p66beta act cooperatively within NuRD, indicating functional interdependence of paralogous subunits rather than redundancy.\",\n      \"evidence\": \"Reciprocal siRNA knockdown with transcriptional repression readouts\",\n      \"pmids\": [\"16415179\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab functional assay without biochemical reconstitution\", \"Quantitative stoichiometry of p66alpha/p66beta in NuRD unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected GATAD2B to developmental signaling by showing Sufu recruits it to Hedgehog target promoters to repress Gli activation, placing NuRD repression downstream of cilium-dependent Hh signaling.\",\n      \"evidence\": \"Mass spectrometry, Co-IP, ChIP, cell-based Hh assays, and zebrafish validation\",\n      \"pmids\": [\"25403183\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether full NuRD complex is recruited with GATAD2B at Hh genes not defined\", \"Direct Sufu-binding interface on GATAD2B unmapped\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified a LOX interaction via the CR2-containing domain promoting nuclear LOX accumulation, hinting at a non-canonical chaperone/localization role.\",\n      \"evidence\": \"Yeast two-hybrid screen, in vitro binding, and co-expression localization in tumor cells\",\n      \"pmids\": [\"25118846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Y2H plus co-localization without functional consequence established\", \"No endogenous interaction or mechanism validated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linked GATAD2B to oncogenic signaling by showing it drives KRAS-mutant lung cancer through c-MYC pathway hyperactivation, broadening its role beyond chromatin repression.\",\n      \"evidence\": \"In vivo functional screen, regulatable KRAS cell models, and c-MYC pathway evaluation\",\n      \"pmids\": [\"30013058\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of GATAD2B-c-MYC interaction not detailed\", \"Whether effect requires NuRD unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined CR1 and CR2 as the domains required for NuRD assembly by showing disease-associated missense variants disrupt partner binding, providing a molecular basis for GATAD2B-related pathology.\",\n      \"evidence\": \"Immunoprecipitation of in vitro-translated wild-type and mutant GATAD2B\",\n      \"pmids\": [\"31949314\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cellular and developmental consequences of variants not tested here\", \"Which specific NuRD subunits each domain contacts not resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed phosphoregulation of GATAD2B by MAP2K6 driving heterochromatin loosening during reprogramming, independent of canonical p38 signaling.\",\n      \"evidence\": \"Kinase substrate assays, kinase-dead epistasis, ChIP, and histone acetylation assays\",\n      \"pmids\": [\"34815549\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphosites on GATAD2B not pinpointed\", \"Mechanism linking phosphorylation to reduced repression unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed GATAD2B can act as a transcriptional co-activator, enhancing Snail binding to G-box elements to promote migration genes, reversing its expected repressive role in a context-specific manner.\",\n      \"evidence\": \"Reciprocal Co-IP, ChIP, luciferase reporters, knockdown, and in vivo mouse metastasis\",\n      \"pmids\": [\"37380643\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How a NuRD subunit switches to co-activation not mechanistically explained\", \"Whether NuRD complex participates unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established GATAD2B-NuRD as an R-loop-dependent responder at DNA double-strand breaks that condenses chromatin to bound DNA end resection and enable HR repair, defining a genome-stability function.\",\n      \"evidence\": \"ChIP, R-loop detection, chromatin fractionation, end resection and HR assays, and loss-of-function\",\n      \"pmids\": [\"38719994\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Recruitment factor reading R-loops not identified\", \"Connection to GATAD2B histone-binding CR2 not directly tested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated GATAD2B is required for zygotic genome activation and pre-implantation development, extending its chromatin role into embryonic genome reprogramming.\",\n      \"evidence\": \"Immunofluorescence, siRNA knockdown, transcriptomics, proteomics, and live embryo imaging in mouse\",\n      \"pmids\": [\"38605678\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct target genes at ZGA not defined\", \"Whether DNA damage phenotype reflects the HR role unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified O-GlcNAcylation by OGT and ITCH-mediated ubiquitination as opposing modifications controlling GATAD2B stability, linking its abundance to cancer stem-cell maintenance.\",\n      \"evidence\": \"O-GlcNAcome proteomics, site mutagenesis, ubiquitination assays, and mammosphere assays\",\n      \"pmids\": [\"40136647\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific O-GlcNAc and ubiquitination residues' interplay not fully mapped\", \"Whether stabilization alters NuRD function not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed GATAD2B controls meiotic spindle assembly and chromosome alignment in oocytes via deacetylation-related gene regulation, connecting its repressive function to faithful chromosome segregation.\",\n      \"evidence\": \"Western blot, immunofluorescence, siRNA microinjection, live imaging, and RNA-seq reanalysis\",\n      \"pmids\": [\"40468728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct spindle-associated mechanism vs transcriptional effect not separated\", \"Targets driving acetylated-protein accumulation not identified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GATAD2B's single biochemical identity as a NuRD histone-reader is reconciled with its context-specific co-activator role and its non-chromatin functions (LOX, c-MYC) remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of GATAD2B within NuRD\", \"No unified mechanism explaining repressor-to-activator switching\", \"Whether developmental and DNA-repair roles share the same complex composition unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 2, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 9]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"Mi-2/NuRD complex\"],\n    \"partners\": [\"MBD2\", \"GATAD2A\", \"SUFU\", \"MAP2K6\", \"OGT\", \"ITCH\", \"SNAI1\", \"MYC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}