{"gene":"ANKRD11","run_date":"2026-06-09T22:02:43","timeline":{"discoveries":[{"year":2011,"finding":"ANKRD11 localizes mainly to the nuclei of neurons and accumulates in discrete nuclear inclusions when neurons are depolarized, suggesting activity-dependent nuclear redistribution linked to neural plasticity.","method":"Subcellular localization by direct imaging in neurons; depolarization experiment","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment in neurons with functional context, single lab, single method","pmids":["21782149"],"is_preprint":false},{"year":2008,"finding":"ANKRD11 is a p53 coactivator: it physically interacts with p53 and with p53 acetyltransferases P/CAF and hADA3, enhances p53 acetylation, increases p53 DNA-binding to the CDKN1A promoter, and elevates CDKN1A (p21) expression; shRNA knockdown of ANKRD11 reduces p53-dependent CDKN1A activation.","method":"Co-immunoprecipitation, shRNA knockdown, luciferase/promoter reporter assay, chromatin immunoprecipitation, western blot for acetylated p53","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP with multiple partners, ChIP, KD phenotype with specific transcriptional readout, multiple orthogonal methods in one study","pmids":["18840648"],"is_preprint":false},{"year":2011,"finding":"ANKRD11 suppresses oncogenic properties of mutant p53 by restoring a native conformation to mutant p53 protein and causing dissociation of the mutant p53–p63 complex, thereby alleviating centrosome abnormalities, mitotic defects, multinucleation, and mesenchymal-like invasion driven by mutant p53.","method":"Inducible expression system, immunoprecipitation to detect p53–p63 complex dissociation, conformational antibody assay, invasion assay, mitosis/centrosome analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP showing complex dissociation, functional cellular phenotype rescue, single lab with multiple orthogonal methods","pmids":["21986947"],"is_preprint":false},{"year":2014,"finding":"Ankrd11 acts as a chromatin regulator controlling histone acetylation during neural development: it associates with chromatin and co-localizes with HDAC3; a point mutation in its HDAC-binding domain (Yoda mouse) alters histone acetylation and expression of Ankrd11 target genes; knockdown-mediated decrease in neural precursor proliferation is rescued by inhibiting histone acetyltransferase activity or by expressing HDAC3.","method":"Chromatin association assay, co-localization with HDAC3, ENU point mutant mouse (Yoda), genetic rescue by HDAC3 overexpression or HAT inhibitor, gene expression analysis in neural precursors","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — chromatin association, co-localization, genetic epistasis via rescue experiments, point mutant mouse model, multiple orthogonal methods, replicated in murine and human systems","pmids":["25556659"],"is_preprint":false},{"year":2014,"finding":"The ANKRD11 C-terminus is required for proteasome-mediated degradation of the protein; wild-type ANKRD11 abundance is tightly regulated during the cell cycle, and pathogenic mutations (all affecting C-terminal regions) cause aberrant accumulation of mutant protein. In silico analysis identifies D-box sequences at the C-terminus as degradation signals.","method":"Cell-cycle analysis of protein abundance, in silico D-box identification, analysis of 11 pathogenic variants in human cells and Yoda mouse","journal":"Human genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — cell-based protein stability experiments across multiple variants, in silico support; no in vitro reconstitution of proteasome degradation","pmids":["25413698"],"is_preprint":false},{"year":2017,"finding":"ANKRD11 regulates pyramidal neuron radial migration and dendritic differentiation in the developing cerebral cortex via epigenetic modification: knockdown suppresses acetylation of p53 and Histone H3, reduces TrkB/BDNF pathway mRNA, and causes the TrkB promoter to be occupied by MeCP2/DNMT1 instead of acetylated H3 and p53; overexpression of TrkB rescues abnormal dendrite growth.","method":"In utero electroporation knockdown, immunofluorescence, ChIP for histone acetylation and promoter occupancy, RT-PCR, TrkB overexpression rescue","journal":"Neurobiology of disease","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo loss-of-function with defined cellular phenotype, ChIP mechanistic data, genetic rescue by TrkB, multiple orthogonal methods","pmids":["29274743"],"is_preprint":false},{"year":2007,"finding":"A missense mutation in a highly conserved region of Ankrd11 (Yoda mouse) causes reduced bone mineral density and craniofacial abnormalities, identifying Ankrd11 as a novel genetic regulator of bone homeostasis; homozygosity is embryonic lethal.","method":"ENU mutagenesis screen, positional cloning, heterozygous and homozygous phenotype analysis (bone mineral density, skull morphology)","journal":"Physiological genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo genetic model with defined skeletal phenotype, positional cloning; mechanism downstream of bone regulation not fully characterized","pmids":["17986521"],"is_preprint":false},{"year":2019,"finding":"ANKRD11/ANCO1 mediates AIB1-YAP-dependent transcriptional repression at the 1q21.3 locus in breast epithelial cells: sequential ChIP and ChIP-seq show that ANCO1 is recruited by AIB1 at TEAD-bound genomic sites and represses a subset of YAP-activated genes; loss of ANCO1 reverts this repression, increases cell size, and enhances YAP-driven aberrant 3D growth.","method":"Sequential ChIP, ChIP-seq, gene expression analysis, 3D growth assay, ANCO1 knockdown","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal ChIP-seq with sequential ChIP validation, loss-of-function with defined transcriptional and cellular phenotype, multiple orthogonal methods in one study","pmids":["31788936"],"is_preprint":false},{"year":2021,"finding":"Conditional deletion of Ankrd11 in neural crest cells causes cleft palate, midfacial hypoplasia, retrognathia, and impaired intramembranous ossification, with reduced proliferation of palatal shelf cells and failure of calvarial ossification centers to expand/fuse, establishing Ankrd11 as a critical regulator of craniofacial bone and palate development.","method":"Neural crest-specific conditional knockout mouse (Ankrd11nchet and Ankrd11ncko), 3D micro-CT imaging, histology, BrdU/EdU proliferation assay","journal":"Frontiers in cell and developmental biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with graded alleles, multiple defined cellular and structural phenotypes, orthogonal imaging and histological methods","pmids":["33996804"],"is_preprint":false},{"year":2023,"finding":"ANKRD11 interacts with HDAC3, and this interaction promotes HDAC3 activity; in a breast cancer model, downregulation of SERPINA3 leads to upregulation of ANKRD11, which binds and activates HDAC3 to confer aromatase inhibitor resistance; HDAC3 inhibition reverses this resistance.","method":"Co-immunoprecipitation, HDAC3 activity assay, gene knockdown/overexpression, drug resistance assays","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP showing ANKRD11-HDAC3 interaction, functional rescue by HDAC3 inhibitor, single lab","pmids":["37414914"],"is_preprint":false},{"year":2023,"finding":"ANKRD11 loss globally increases H3K27Ac at breast-cancer-specific enhancers enriched for AP-1, TEAD, STAT3, and NFκB motifs, activating genes in PI3K-AKT, EMT, and senescence pathways; ChIP-seq in ANCO1-depleted early-stage TNBC cells identifies ANCO1 as a broad chromatin repressor.","method":"ChIP-seq for H3K27Ac, shRNA knockdown of ANCO1, 3D invasion assay, xenograft model","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq with defined chromatin phenotype, in vivo xenograft, single lab","pmids":["37511268"],"is_preprint":false},{"year":2022,"finding":"Pathogenic ANKRD11 missense variants cause loss-of-function via two independent mechanisms: reduced protein stability (proteolytic degradation) or decreased transcriptional repression activity; missense variants significantly cluster in repression domain 2 at the ANKRD11 C-terminus.","method":"Cell-based protein stability assays, transcriptional activity reporter assays, proteasome inhibition experiments, clustering analysis of variant locations","journal":"Genetics in medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-based functional assays for 10 variants with two orthogonal functional readouts; single lab","pmids":["35833929"],"is_preprint":false},{"year":2024,"finding":"The minor spliceosomal protein 65K/RNPC3 interacts with ANKRD11, which acts as a bridging factor facilitating co-occupancy of HDAC3 and 65K on chromatin; ANKRD11 knockdown simultaneously reduces HDAC3 and 65K chromatin binding and decreases H3K9 deacetylation at their common target loci, altering gene expression; the interaction is conserved in both Drosophila and human cells, and the middle uncharacterized domain of HsANKRD11 mediates the Hs65K–HDAC3 association.","method":"Affinity purification in Drosophila lysates, CRISPR/Cas9 deletion mutants, CUT&Tag chromatin profiling, Co-IP in human cells, domain mapping, histone modification analysis","journal":"Advanced science","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — affinity purification, CUT&Tag, Co-IP, genetic deletion strains, domain mutagenesis, conserved in two organisms, multiple orthogonal methods","pmids":["38837887"],"is_preprint":false},{"year":2025,"finding":"ANKRD11 binds the cohesin complex via a short N-terminal peptide fragment with high affinity; the crystal structure of this peptide in complex with cohesin shows ANKRD11 competes with CTCF for cohesin binding; a single point mutation Y347A specifically disrupts ANKRD11–cohesin interaction, perturbs gene expression in mouse embryonic stem cells, and causes neural and craniofacial anomalies in Y347A knock-in mice.","method":"Crystal structure determination, biochemical binding assays, site-directed mutagenesis (Y347A), gene expression analysis in mESCs, knock-in mouse model","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure, in vitro binding competition assay, mutagenesis, knock-in mouse phenotype; multiple orthogonal methods in one study","pmids":["39847329"],"is_preprint":false},{"year":2023,"finding":"A bipartite nuclear localization signal (bNLS) between residues 53–87 of ANKRD11 mediates nuclear import via two binding sites for Importin α1; this bNLS is sufficient to drive nuclear import of GFP in HeLa cells and necessary for endogenous ANKRD11 nuclear localization; clinical variants within the bNLS provide a pathogenic mechanism for some KBG mutations.","method":"Site-directed mutagenesis, GFP-fusion nuclear import assay in HeLa cells, biochemical binding to Importin α1, immunofluorescence","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis + functional import assay + Importin binding, single lab, multiple orthogonal methods","pmids":["37290286"],"is_preprint":false},{"year":2024,"finding":"Conditional knockout of Ankrd11 in murine embryonic neural crest cells causes persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility due to aberrant cardiac neural crest cell organization and outflow tract septation failure; knockout impairs expression of transcription factors, chromatin remodelers, and mTOR/BMP/TGF-β signaling pathways in cardiac neural crest cells.","method":"Neural crest-specific conditional knockout mouse, echocardiography, histology, transcriptome analysis of cardiac neural crest cells","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined cardiac structural and functional phenotypes, pathway analysis in sorted cell population, multiple readouts in one study","pmids":["38951500"],"is_preprint":false},{"year":2025,"finding":"ANKRD11 promotes rRNA expression and translation by upregulating SETD5 expression: ANKRD11 interacts with the Setd5 promoter and recruits WDR5 (a component of the H3K4 methyltransferase complex), increasing H3K4 methylation at the Setd5 promoter; ANKRD11 deficiency reduces H3K4me at Setd5, decreases SETD5 and rRNA levels, and impairs translation; overexpression of ANKRD11 or SETD5 rescues rRNA levels and translation.","method":"ChIP for H3K4 methylation at Setd5 promoter, Co-IP (ANKRD11–WDR5), rRNA quantification, polysome profiling/translation assay, overexpression rescue","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP, Co-IP, functional rescue; single lab, mechanistic pathway placement via genetic rescue","pmids":["40520101"],"is_preprint":false},{"year":2020,"finding":"ANKRD11 loss-of-function variants reduce CDKN1A/p21 promoter-driven luciferase activity; re-introduction of wild-type ANKRD11 but not pathogenic variants (p.Lys1347del or p.Leu2143Val) restores p21 promoter activity and endogenous p21 mRNA levels, confirming the transcriptional activation function of ANKRD11 toward CDKN1A.","method":"p21-promoter luciferase reporter assay, RT-PCR for endogenous CDKN1A mRNA, re-expression of wild-type vs. mutant ANKRD11","journal":"American journal of medical genetics. Part A","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay with isogenic mutant rescue, single lab, two orthogonal readouts","pmids":["33354850"],"is_preprint":false},{"year":2024,"finding":"A truncating frameshift ANKRD11 variant (p.Y761Qfs*20) escapes nonsense-mediated mRNA decay and produces a truncated protein that accumulates at higher levels than full-length ANKRD11 and localizes predominantly to the nucleus (unlike wild-type which distributes in both nucleus and cytoplasm); the truncated protein significantly reduces CDKN1A/p21-promoter luciferase activity and endogenous p21 mRNA, consistent with dominant-negative loss of transcriptional activation.","method":"NMD escape assay, immunofluorescence localization, p21-promoter luciferase reporter assay, RT-PCR, western blot for protein levels","journal":"Heliyon","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal cell-based assays, single lab, single variant studied","pmids":["38515699"],"is_preprint":false},{"year":2012,"finding":"The ANKRD11 promoter is specifically methylated at three CpG sites in a 19 bp region in breast tumors compared to normal tissue; treatment of breast cancer cell lines with DNA demethylating agents upregulates ANKRD11 expression, linking promoter methylation to transcriptional silencing of ANKRD11.","method":"SEQUENOM Epityper methylation analysis, dual-luciferase reporter assay for promoter activity, demethylating agent treatment with expression measurement","journal":"European journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative methylation mapping, luciferase reporter, pharmacological demethylation rescue; single lab","pmids":["22538187"],"is_preprint":false}],"current_model":"ANKRD11 is a large nuclear chromatin regulator that controls gene expression by (1) acting as a p53 coactivator through association with acetyltransferases P/CAF and hADA3 to enhance p53 acetylation and CDKN1A transcription, (2) modulating histone acetylation via HDAC3, with which it forms a complex that also recruits the minor spliceosomal factor 65K/RNPC3 to co-regulate chromatin deacetylation, (3) binding the cohesin complex through an N-terminal peptide to compete with CTCF and regulate developmental gene expression, (4) promoting SETD5 expression via WDR5/H3K4 methylation to sustain rRNA production and translation, and (5) suppressing oncogenic mutant p53 by restoring its native conformation and disrupting mutant p53–p63 complexes; nuclear localization depends on a bipartite NLS (residues 53–87) that binds Importin α1, protein abundance is regulated by C-terminal D-box-mediated proteasomal degradation, and in vivo loss-of-function in neural crest cells causes craniofacial, skeletal, palatal, and cardiac outflow tract defects, while in neurons it governs histone acetylation-dependent dendrite growth and migration through the BDNF/TrkB pathway."},"narrative":{"mechanistic_narrative":"ANKRD11 is a large nuclear chromatin regulator that controls developmental gene expression by coupling transcription factors to histone-modifying and chromatin-architecture machinery [PMID:25556659, PMID:31788936, PMID:39847329]. It functions as a p53 coactivator, physically associating with p53 and the acetyltransferases P/CAF and hADA3 to enhance p53 acetylation, p53 occupancy of the CDKN1A promoter, and p21 expression [PMID:18840648]; loss-of-function and dominant-negative pathogenic variants reduce CDKN1A promoter activity and p21 transcription [PMID:33354850, PMID:38515699]. Through its HDAC-binding domain it associates with chromatin and HDAC3 to set histone acetylation levels at target genes during neural development [PMID:25556659], and it bridges HDAC3 with the minor spliceosomal protein 65K/RNPC3 to drive their co-occupancy and H3K9 deacetylation at shared loci [PMID:38837887]. ANKRD11 also acts as a broad enhancer repressor, recruited by AIB1 to TEAD-bound sites to restrain YAP-activated transcription, and its loss globally elevates H3K27 acetylation at oncogenic enhancers [PMID:31788936, PMID:37511268]. Independently, a short N-terminal peptide binds the cohesin complex and competes with CTCF, linking ANKRD11 to genome architecture, while at the Setd5 promoter it recruits WDR5 to deposit H3K4 methylation and sustain rRNA production and translation [PMID:39847329, PMID:40520101]. Nuclear import depends on a bipartite NLS (residues 53–87) that binds Importin α1, and protein abundance is controlled by C-terminal proteasomal degradation signals [PMID:37290286, PMID:25413698]. In vivo, loss of Ankrd11 in neural crest cells produces craniofacial, palatal, skeletal, and cardiac outflow-tract defects, and in cortical neurons it governs histone-acetylation-dependent dendrite growth and radial migration via the BDNF/TrkB pathway [PMID:33996804, PMID:38951500, PMID:29274743]; pathogenic ANKRD11 variants cause KBG syndrome through reduced protein stability or impaired transcriptional repression [PMID:35833929, PMID:37290286].","teleology":[{"year":2007,"claim":"Established Ankrd11 as a genetic regulator of skeletal and craniofacial development in vivo, before any molecular mechanism was known.","evidence":"ENU mutagenesis screen and positional cloning of the Yoda missense mouse with bone density and skull phenotypes","pmids":["17986521"],"confidence":"Medium","gaps":["Molecular pathway downstream of bone regulation not defined","Homozygous lethality precluded analysis of full loss of function"]},{"year":2008,"claim":"Defined a first molecular function — that ANKRD11 coactivates p53-dependent transcription — by linking it to acetyltransferases and a defined transcriptional readout.","evidence":"Reciprocal Co-IP with p53/P/CAF/hADA3, ChIP at CDKN1A, shRNA knockdown, acetyl-p53 western blot","pmids":["18840648"],"confidence":"High","gaps":["Direct enzymatic versus scaffolding contribution to acetylation not separated","Structural basis of p53/P/CAF binding unknown"]},{"year":2011,"claim":"Extended the p53 link to oncogenic mutant p53, showing ANKRD11 can restore native conformation and dissociate mutant p53–p63 complexes to suppress malignant phenotypes.","evidence":"Inducible expression, conformational antibody and Co-IP assays, invasion and centrosome/mitosis analysis","pmids":["21986947"],"confidence":"Medium","gaps":["Mechanism of conformational restoration not biochemically resolved","Single-lab cellular study"]},{"year":2011,"claim":"Showed ANKRD11 is predominantly nuclear in neurons and redistributes into nuclear inclusions on depolarization, hinting at activity-dependent regulation relevant to neural plasticity.","evidence":"Direct imaging and depolarization in neurons","pmids":["21782149"],"confidence":"Medium","gaps":["Functional significance of nuclear inclusions not established","Single method, single lab"]},{"year":2012,"claim":"Linked ANKRD11 silencing to cancer by showing its promoter is methylated in breast tumors and reactivated by demethylation.","evidence":"Epityper methylation mapping, luciferase promoter assay, demethylating-agent treatment","pmids":["22538187"],"confidence":"Medium","gaps":["Causal role of silencing in tumorigenesis not tested","Downstream consequences of loss not addressed in this study"]},{"year":2014,"claim":"Identified the chromatin/HDAC3 axis as ANKRD11's developmental mechanism, with genetic epistasis showing histone acetylation control drives neural precursor proliferation.","evidence":"Chromatin association, HDAC3 co-localization, Yoda HDAC-binding-domain point mutant, rescue by HDAC3 or HAT inhibition","pmids":["25556659"],"confidence":"High","gaps":["Direct target gene set incompletely defined","How ANKRD11 selects loci not resolved"]},{"year":2014,"claim":"Defined how ANKRD11 abundance is controlled, attributing pathogenic accumulation to disruption of C-terminal D-box degradation signals.","evidence":"Cell-cycle protein abundance analysis, in silico D-box identification, analysis of 11 pathogenic variants","pmids":["25413698"],"confidence":"Medium","gaps":["No in vitro reconstitution of proteasomal degradation","Responsible E3 ligase not identified"]},{"year":2017,"claim":"Placed ANKRD11 in a neuronal epigenetic circuit, showing it maintains acetylated H3/p53 at the TrkB promoter to drive BDNF/TrkB-dependent migration and dendrite growth.","evidence":"In utero electroporation knockdown, ChIP for acetylation and MeCP2/DNMT1 occupancy, TrkB overexpression rescue","pmids":["29274743"],"confidence":"High","gaps":["Direct versus indirect occupancy of the TrkB promoter not separated","Link to human neurodevelopmental phenotypes inferred from mouse"]},{"year":2019,"claim":"Revealed a repressive chromatin function: ANKRD11/ANCO1 is recruited by AIB1 to TEAD sites to repress YAP-activated genes and restrain aberrant growth.","evidence":"Sequential ChIP, ChIP-seq, knockdown, 3D growth assay in breast epithelial cells","pmids":["31788936"],"confidence":"High","gaps":["Mechanism of repression at TEAD sites not defined","Relationship to HDAC3-based repression not integrated"]},{"year":2020,"claim":"Confirmed clinically that pathogenic ANKRD11 variants abolish its CDKN1A transcriptional activation, validating the p53/p21 readout as disease-relevant.","evidence":"p21-promoter luciferase and endogenous p21 RT-PCR with wild-type versus mutant re-expression","pmids":["33354850"],"confidence":"Medium","gaps":["Only two variants tested","In vivo consequence of impaired p21 activation not shown"]},{"year":2021,"claim":"Demonstrated a cell-autonomous requirement for Ankrd11 in neural crest for craniofacial bone and palate formation, with reduced precursor proliferation.","evidence":"Neural crest-specific conditional knockout, micro-CT, histology, BrdU/EdU proliferation assays","pmids":["33996804"],"confidence":"High","gaps":["Molecular targets mediating the proliferation defect not identified","Chromatin mechanism not directly tested in this model"]},{"year":2022,"claim":"Resolved the genotype–mechanism relationship for KBG syndrome, showing missense variants act by either reduced stability or impaired repression and cluster in C-terminal repression domain 2.","evidence":"Cell-based stability and transcriptional-repression assays for 10 variants, variant clustering analysis","pmids":["35833929"],"confidence":"Medium","gaps":["Two mechanisms not linked to distinct clinical outcomes","Single-lab functional assays"]},{"year":2023,"claim":"Mapped the nuclear import determinant, identifying a bipartite NLS that binds Importin α1 and is required for endogenous nuclear localization.","evidence":"Site-directed mutagenesis, GFP nuclear-import assay, Importin α1 binding, immunofluorescence in HeLa","pmids":["37290286"],"confidence":"Medium","gaps":["Regulation of import not addressed","Single-lab study"]},{"year":2023,"claim":"Connected ANKRD11–HDAC3 activation to therapy resistance, showing a SERPINA3–ANKRD11–HDAC3 axis drives aromatase inhibitor resistance.","evidence":"Co-IP, HDAC3 activity assay, knockdown/overexpression, drug resistance assays","pmids":["37414914"],"confidence":"Medium","gaps":["How ANKRD11 binding stimulates HDAC3 activity not defined","Single-lab cancer model"]},{"year":2023,"claim":"Defined ANKRD11/ANCO1 as a broad enhancer repressor, with loss elevating H3K27Ac at oncogenic enhancers enriched for AP-1, TEAD, STAT3 and NFκB motifs.","evidence":"H3K27Ac ChIP-seq in ANCO1-depleted TNBC cells, 3D invasion, xenograft","pmids":["37511268"],"confidence":"Medium","gaps":["Direct recruitment mechanism to each enhancer class unresolved","Single-lab study"]},{"year":2024,"claim":"Established ANKRD11 as a conserved bridging factor coupling HDAC3 to the minor spliceosomal protein 65K/RNPC3 for chromatin co-occupancy and H3K9 deacetylation.","evidence":"Affinity purification in Drosophila, CRISPR deletions, Co-IP and CUT&Tag in human cells, domain mapping","pmids":["38837887"],"confidence":"High","gaps":["Functional consequence of linking splicing factor to chromatin deacetylation unclear","Target gene network incompletely defined"]},{"year":2024,"claim":"Showed a truncating frameshift variant escapes NMD, over-accumulates as a nuclear-restricted protein, and dominant-negatively impairs p21 activation.","evidence":"NMD escape assay, localization, p21 luciferase, RT-PCR, western blot","pmids":["38515699"],"confidence":"Medium","gaps":["Single variant studied","Dominant-negative mechanism inferred, not structurally shown"]},{"year":2024,"claim":"Extended the neural crest requirement to the heart, showing Ankrd11 controls cardiac outflow tract septation through transcription/chromatin and mTOR/BMP/TGF-β programs.","evidence":"Neural crest conditional knockout, echocardiography, histology, cardiac neural crest transcriptomics","pmids":["38951500"],"confidence":"High","gaps":["Direct ANKRD11 targets in cardiac neural crest not pinpointed","Connection to specific chromatin complexes not tested in this model"]},{"year":2025,"claim":"Provided structural and genetic proof that ANKRD11 binds cohesin via an N-terminal peptide and competes with CTCF, with a single Y347A mutation perturbing gene expression and causing developmental anomalies.","evidence":"Crystal structure, biochemical binding/competition, Y347A knock-in mouse, mESC expression analysis","pmids":["39847329"],"confidence":"High","gaps":["Genome-wide map of ANKRD11-dependent cohesin/CTCF sites not reported","Relationship between cohesin binding and HDAC3/repression functions not integrated"]},{"year":2025,"claim":"Identified a ribosome-biogenesis function in which ANKRD11 recruits WDR5 to the Setd5 promoter to drive H3K4 methylation, SETD5 expression, rRNA production and translation.","evidence":"ChIP for H3K4me at Setd5, ANKRD11–WDR5 Co-IP, rRNA quantification, polysome profiling, rescue","pmids":["40520101"],"confidence":"Medium","gaps":["Direct versus scaffolded WDR5 recruitment not resolved","Tissue specificity of this axis not defined"]},{"year":null,"claim":"How ANKRD11's distinct activities — p53 coactivation, HDAC3/65K-mediated deacetylation, WDR5/H3K4 activation, ANCO1 enhancer repression, and cohesin/CTCF competition — are coordinated at the genome and which dominate in each developmental context remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model integrating activating and repressive chromatin functions","No single study mapping all ANKRD11 partners on shared loci","Domain-level partitioning of the multiple interactions only partially mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,7,10,17]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[12,16,1]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1,7,13]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[3,12]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,14,18]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[3,12,13]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[3,10,12,13]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,7,16,17]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[8,15,5,6]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[16]}],"complexes":["cohesin complex","ANKRD11–HDAC3–65K/RNPC3 complex"],"partners":["TP53","PCAF","TADA3","HDAC3","RNPC3","WDR5","NCOA3","KPNA"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6UB99","full_name":"Ankyrin repeat domain-containing protein 11","aliases":["Ankyrin repeat-containing cofactor 1"],"length_aa":2663,"mass_kda":297.9,"function":"Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (By similarity). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (PubMed:15184363). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). 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A second example.","date":"1989","source":"Annales de genetique","url":"https://pubmed.ncbi.nlm.nih.gov/2486064","citation_count":9,"is_preprint":false},{"pmid":"38951500","id":"PMC_38951500","title":"The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38951500","citation_count":8,"is_preprint":false},{"pmid":"39135054","id":"PMC_39135054","title":"Insights into the ANKRD11 variants and short-stature phenotype through literature review and ClinVar database search.","date":"2024","source":"Orphanet journal of rare diseases","url":"https://pubmed.ncbi.nlm.nih.gov/39135054","citation_count":8,"is_preprint":false},{"pmid":"12688594","id":"PMC_12688594","title":"Higher degree of chromosome mosaicism in preimplantation embryos from carriers of robertsonian translocation t(13;14) in comparison with embryos from karyotypically normal IVF patients.","date":"2003","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12688594","citation_count":7,"is_preprint":false},{"pmid":"37511268","id":"PMC_37511268","title":"Loss of ANCO1 Expression Regulates Chromatin Accessibility and Drives Progression of Early-Stage Triple-Negative Breast Cancer.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37511268","citation_count":6,"is_preprint":false},{"pmid":"36628575","id":"PMC_36628575","title":"Deletion of first noncoding exon in ANKRD11 leads to KBG syndrome.","date":"2023","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/36628575","citation_count":6,"is_preprint":false},{"pmid":"32820523","id":"PMC_32820523","title":"[Analysis of ANKRD11 gene variant in a family affected with KBG syndrome].","date":"2020","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32820523","citation_count":6,"is_preprint":false},{"pmid":"37064352","id":"PMC_37064352","title":"The clinical significance of computed tomography texture features of renal cell carcinoma in predicting pathological T1-3 staging.","date":"2023","source":"Quantitative imaging in medicine and surgery","url":"https://pubmed.ncbi.nlm.nih.gov/37064352","citation_count":6,"is_preprint":false},{"pmid":"22527900","id":"PMC_22527900","title":"Sperm meiotic segregation, aneuploidy and high risk of delivering an affected offspring in carriers of non-Robertsonian translocation t(13;15).","date":"2012","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22527900","citation_count":6,"is_preprint":false},{"pmid":"34247373","id":"PMC_34247373","title":"[Gender difference in clinical manifestations of KBG syndrome due to variants of ANKRD11 gene].","date":"2021","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34247373","citation_count":5,"is_preprint":false},{"pmid":"33653342","id":"PMC_33653342","title":"A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome.","date":"2021","source":"BMC medical genomics","url":"https://pubmed.ncbi.nlm.nih.gov/33653342","citation_count":5,"is_preprint":false},{"pmid":"29375862","id":"PMC_29375862","title":"The first antenatal diagnosis of KBG syndrome: a microdeletion at chromosome 16q24.2q24.3 containing multiple genes including ANKRD11 associated with the disorder.","date":"2017","source":"Clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/29375862","citation_count":5,"is_preprint":false},{"pmid":"7327568","id":"PMC_7327568","title":"Proximal trisomy 13. A family with balanced reciprocal translocation t(8;13) in seven members and Robertsonian translocation t(13;14) in three members.","date":"1981","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/7327568","citation_count":5,"is_preprint":false},{"pmid":"32575463","id":"PMC_32575463","title":"Transcriptome Analysis of High-NUE (T29) and Low-NUE (T13) Genotypes Identified Different Responsive Patterns Involved in Nitrogen Stress in Ramie (Boehmeria nivea (L.) Gaudich).","date":"2020","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/32575463","citation_count":4,"is_preprint":false},{"pmid":"39847329","id":"PMC_39847329","title":"ANKRD11 binding to cohesin suggests a connection between KBG syndrome and Cornelia de Lange syndrome.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/39847329","citation_count":3,"is_preprint":false},{"pmid":"37290286","id":"PMC_37290286","title":"Identification and functional characterization of a bipartite nuclear localization signal in ANKRD11.","date":"2023","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/37290286","citation_count":3,"is_preprint":false},{"pmid":"38689824","id":"PMC_38689824","title":"Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center.","date":"2024","source":"Pathology oncology research : POR","url":"https://pubmed.ncbi.nlm.nih.gov/38689824","citation_count":3,"is_preprint":false},{"pmid":"33052080","id":"PMC_33052080","title":"Cryptic t(15;17) acute promyelocytic leukemia with a karyotype of add(11)(p15) and t(13,20)- A case report with a literature review.","date":"2021","source":"Bosnian journal of basic medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33052080","citation_count":3,"is_preprint":false},{"pmid":"27698593","id":"PMC_27698593","title":"Hypofractionated accelerated radiotherapy in T1-3 N0 cancer of the larynx: A prospective cohort study with historical controls.","date":"2016","source":"Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/27698593","citation_count":3,"is_preprint":false},{"pmid":"8908170","id":"PMC_8908170","title":"Unusual chromosome aberration, t(13;14)(q32;q32.3), in a case of essential thrombocythemia with extreme thrombocytosis.","date":"1996","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/8908170","citation_count":3,"is_preprint":false},{"pmid":"40520101","id":"PMC_40520101","title":"KBG syndrome-associated protein ANKRD11 regulates SETD5 expression to modulate rRNA levels and translation.","date":"2025","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/40520101","citation_count":2,"is_preprint":false},{"pmid":"40248734","id":"PMC_40248734","title":"ANKRD11 as a potential biomarker for brain metastasis from lung adenocarcinoma via cerebrospinal fluid liquid biopsy.","date":"2025","source":"Translational lung cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/40248734","citation_count":2,"is_preprint":false},{"pmid":"38515699","id":"PMC_38515699","title":"Functional investigation of a novel ANKRD11 frameshift variant identified in a Chinese family with KBG syndrome.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38515699","citation_count":2,"is_preprint":false},{"pmid":"37534006","id":"PMC_37534006","title":"Urothelial bladder afferents selectively project to L6/S1 levels and are more peptidergic than those projecting to the T13/L1 levels in female rats.","date":"2023","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/37534006","citation_count":2,"is_preprint":false},{"pmid":"32081942","id":"PMC_32081942","title":"T-13 and T-26, the novel taxanes with improved oral bioavailability in rats.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32081942","citation_count":2,"is_preprint":false},{"pmid":"27382241","id":"PMC_27382241","title":"A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15)(p11.2;q22.1).","date":"2016","source":"Journal of human reproductive sciences","url":"https://pubmed.ncbi.nlm.nih.gov/27382241","citation_count":2,"is_preprint":false},{"pmid":"10494096","id":"PMC_10494096","title":"Detection of a cryptic translocation t(13;20)(q34;p13) in an unexplained case of MCA/MR: value of FISH over high resolution banding.","date":"1999","source":"American journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10494096","citation_count":2,"is_preprint":false},{"pmid":"40004465","id":"PMC_40004465","title":"16q24.3 Microdeletions Disrupting Upstream Non-Coding Region of ANKRD11 Cause KBG Syndrome.","date":"2025","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/40004465","citation_count":1,"is_preprint":false},{"pmid":"40574944","id":"PMC_40574944","title":"A novel heterozygous mutation of ANKRD11 causes KBG syndrome in a preterm neonate: a case report and literature review.","date":"2025","source":"Frontiers in pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/40574944","citation_count":1,"is_preprint":false},{"pmid":"36584991","id":"PMC_36584991","title":"[Clinical and genetic analysis of three children with KBG syndrome due to novel variants of ANKRD11 gene].","date":"2023","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36584991","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":45288,"output_tokens":5306,"usd":0.107727,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13751,"output_tokens":5718,"usd":0.105853,"stage2_stop_reason":"end_turn"},"total_usd":0.21358,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"ANKRD11 localizes mainly to the nuclei of neurons and accumulates in discrete nuclear inclusions when neurons are depolarized, suggesting activity-dependent nuclear redistribution linked to neural plasticity.\",\n      \"method\": \"Subcellular localization by direct imaging in neurons; depolarization experiment\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment in neurons with functional context, single lab, single method\",\n      \"pmids\": [\"21782149\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"ANKRD11 is a p53 coactivator: it physically interacts with p53 and with p53 acetyltransferases P/CAF and hADA3, enhances p53 acetylation, increases p53 DNA-binding to the CDKN1A promoter, and elevates CDKN1A (p21) expression; shRNA knockdown of ANKRD11 reduces p53-dependent CDKN1A activation.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown, luciferase/promoter reporter assay, chromatin immunoprecipitation, western blot for acetylated p53\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP with multiple partners, ChIP, KD phenotype with specific transcriptional readout, multiple orthogonal methods in one study\",\n      \"pmids\": [\"18840648\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ANKRD11 suppresses oncogenic properties of mutant p53 by restoring a native conformation to mutant p53 protein and causing dissociation of the mutant p53–p63 complex, thereby alleviating centrosome abnormalities, mitotic defects, multinucleation, and mesenchymal-like invasion driven by mutant p53.\",\n      \"method\": \"Inducible expression system, immunoprecipitation to detect p53–p63 complex dissociation, conformational antibody assay, invasion assay, mitosis/centrosome analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP showing complex dissociation, functional cellular phenotype rescue, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"21986947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Ankrd11 acts as a chromatin regulator controlling histone acetylation during neural development: it associates with chromatin and co-localizes with HDAC3; a point mutation in its HDAC-binding domain (Yoda mouse) alters histone acetylation and expression of Ankrd11 target genes; knockdown-mediated decrease in neural precursor proliferation is rescued by inhibiting histone acetyltransferase activity or by expressing HDAC3.\",\n      \"method\": \"Chromatin association assay, co-localization with HDAC3, ENU point mutant mouse (Yoda), genetic rescue by HDAC3 overexpression or HAT inhibitor, gene expression analysis in neural precursors\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — chromatin association, co-localization, genetic epistasis via rescue experiments, point mutant mouse model, multiple orthogonal methods, replicated in murine and human systems\",\n      \"pmids\": [\"25556659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The ANKRD11 C-terminus is required for proteasome-mediated degradation of the protein; wild-type ANKRD11 abundance is tightly regulated during the cell cycle, and pathogenic mutations (all affecting C-terminal regions) cause aberrant accumulation of mutant protein. In silico analysis identifies D-box sequences at the C-terminus as degradation signals.\",\n      \"method\": \"Cell-cycle analysis of protein abundance, in silico D-box identification, analysis of 11 pathogenic variants in human cells and Yoda mouse\",\n      \"journal\": \"Human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — cell-based protein stability experiments across multiple variants, in silico support; no in vitro reconstitution of proteasome degradation\",\n      \"pmids\": [\"25413698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"ANKRD11 regulates pyramidal neuron radial migration and dendritic differentiation in the developing cerebral cortex via epigenetic modification: knockdown suppresses acetylation of p53 and Histone H3, reduces TrkB/BDNF pathway mRNA, and causes the TrkB promoter to be occupied by MeCP2/DNMT1 instead of acetylated H3 and p53; overexpression of TrkB rescues abnormal dendrite growth.\",\n      \"method\": \"In utero electroporation knockdown, immunofluorescence, ChIP for histone acetylation and promoter occupancy, RT-PCR, TrkB overexpression rescue\",\n      \"journal\": \"Neurobiology of disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo loss-of-function with defined cellular phenotype, ChIP mechanistic data, genetic rescue by TrkB, multiple orthogonal methods\",\n      \"pmids\": [\"29274743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"A missense mutation in a highly conserved region of Ankrd11 (Yoda mouse) causes reduced bone mineral density and craniofacial abnormalities, identifying Ankrd11 as a novel genetic regulator of bone homeostasis; homozygosity is embryonic lethal.\",\n      \"method\": \"ENU mutagenesis screen, positional cloning, heterozygous and homozygous phenotype analysis (bone mineral density, skull morphology)\",\n      \"journal\": \"Physiological genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo genetic model with defined skeletal phenotype, positional cloning; mechanism downstream of bone regulation not fully characterized\",\n      \"pmids\": [\"17986521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ANKRD11/ANCO1 mediates AIB1-YAP-dependent transcriptional repression at the 1q21.3 locus in breast epithelial cells: sequential ChIP and ChIP-seq show that ANCO1 is recruited by AIB1 at TEAD-bound genomic sites and represses a subset of YAP-activated genes; loss of ANCO1 reverts this repression, increases cell size, and enhances YAP-driven aberrant 3D growth.\",\n      \"method\": \"Sequential ChIP, ChIP-seq, gene expression analysis, 3D growth assay, ANCO1 knockdown\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal ChIP-seq with sequential ChIP validation, loss-of-function with defined transcriptional and cellular phenotype, multiple orthogonal methods in one study\",\n      \"pmids\": [\"31788936\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Conditional deletion of Ankrd11 in neural crest cells causes cleft palate, midfacial hypoplasia, retrognathia, and impaired intramembranous ossification, with reduced proliferation of palatal shelf cells and failure of calvarial ossification centers to expand/fuse, establishing Ankrd11 as a critical regulator of craniofacial bone and palate development.\",\n      \"method\": \"Neural crest-specific conditional knockout mouse (Ankrd11nchet and Ankrd11ncko), 3D micro-CT imaging, histology, BrdU/EdU proliferation assay\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with graded alleles, multiple defined cellular and structural phenotypes, orthogonal imaging and histological methods\",\n      \"pmids\": [\"33996804\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ANKRD11 interacts with HDAC3, and this interaction promotes HDAC3 activity; in a breast cancer model, downregulation of SERPINA3 leads to upregulation of ANKRD11, which binds and activates HDAC3 to confer aromatase inhibitor resistance; HDAC3 inhibition reverses this resistance.\",\n      \"method\": \"Co-immunoprecipitation, HDAC3 activity assay, gene knockdown/overexpression, drug resistance assays\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP showing ANKRD11-HDAC3 interaction, functional rescue by HDAC3 inhibitor, single lab\",\n      \"pmids\": [\"37414914\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ANKRD11 loss globally increases H3K27Ac at breast-cancer-specific enhancers enriched for AP-1, TEAD, STAT3, and NFκB motifs, activating genes in PI3K-AKT, EMT, and senescence pathways; ChIP-seq in ANCO1-depleted early-stage TNBC cells identifies ANCO1 as a broad chromatin repressor.\",\n      \"method\": \"ChIP-seq for H3K27Ac, shRNA knockdown of ANCO1, 3D invasion assay, xenograft model\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq with defined chromatin phenotype, in vivo xenograft, single lab\",\n      \"pmids\": [\"37511268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Pathogenic ANKRD11 missense variants cause loss-of-function via two independent mechanisms: reduced protein stability (proteolytic degradation) or decreased transcriptional repression activity; missense variants significantly cluster in repression domain 2 at the ANKRD11 C-terminus.\",\n      \"method\": \"Cell-based protein stability assays, transcriptional activity reporter assays, proteasome inhibition experiments, clustering analysis of variant locations\",\n      \"journal\": \"Genetics in medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-based functional assays for 10 variants with two orthogonal functional readouts; single lab\",\n      \"pmids\": [\"35833929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The minor spliceosomal protein 65K/RNPC3 interacts with ANKRD11, which acts as a bridging factor facilitating co-occupancy of HDAC3 and 65K on chromatin; ANKRD11 knockdown simultaneously reduces HDAC3 and 65K chromatin binding and decreases H3K9 deacetylation at their common target loci, altering gene expression; the interaction is conserved in both Drosophila and human cells, and the middle uncharacterized domain of HsANKRD11 mediates the Hs65K–HDAC3 association.\",\n      \"method\": \"Affinity purification in Drosophila lysates, CRISPR/Cas9 deletion mutants, CUT&Tag chromatin profiling, Co-IP in human cells, domain mapping, histone modification analysis\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — affinity purification, CUT&Tag, Co-IP, genetic deletion strains, domain mutagenesis, conserved in two organisms, multiple orthogonal methods\",\n      \"pmids\": [\"38837887\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ANKRD11 binds the cohesin complex via a short N-terminal peptide fragment with high affinity; the crystal structure of this peptide in complex with cohesin shows ANKRD11 competes with CTCF for cohesin binding; a single point mutation Y347A specifically disrupts ANKRD11–cohesin interaction, perturbs gene expression in mouse embryonic stem cells, and causes neural and craniofacial anomalies in Y347A knock-in mice.\",\n      \"method\": \"Crystal structure determination, biochemical binding assays, site-directed mutagenesis (Y347A), gene expression analysis in mESCs, knock-in mouse model\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure, in vitro binding competition assay, mutagenesis, knock-in mouse phenotype; multiple orthogonal methods in one study\",\n      \"pmids\": [\"39847329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"A bipartite nuclear localization signal (bNLS) between residues 53–87 of ANKRD11 mediates nuclear import via two binding sites for Importin α1; this bNLS is sufficient to drive nuclear import of GFP in HeLa cells and necessary for endogenous ANKRD11 nuclear localization; clinical variants within the bNLS provide a pathogenic mechanism for some KBG mutations.\",\n      \"method\": \"Site-directed mutagenesis, GFP-fusion nuclear import assay in HeLa cells, biochemical binding to Importin α1, immunofluorescence\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis + functional import assay + Importin binding, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"37290286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Conditional knockout of Ankrd11 in murine embryonic neural crest cells causes persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility due to aberrant cardiac neural crest cell organization and outflow tract septation failure; knockout impairs expression of transcription factors, chromatin remodelers, and mTOR/BMP/TGF-β signaling pathways in cardiac neural crest cells.\",\n      \"method\": \"Neural crest-specific conditional knockout mouse, echocardiography, histology, transcriptome analysis of cardiac neural crest cells\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined cardiac structural and functional phenotypes, pathway analysis in sorted cell population, multiple readouts in one study\",\n      \"pmids\": [\"38951500\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ANKRD11 promotes rRNA expression and translation by upregulating SETD5 expression: ANKRD11 interacts with the Setd5 promoter and recruits WDR5 (a component of the H3K4 methyltransferase complex), increasing H3K4 methylation at the Setd5 promoter; ANKRD11 deficiency reduces H3K4me at Setd5, decreases SETD5 and rRNA levels, and impairs translation; overexpression of ANKRD11 or SETD5 rescues rRNA levels and translation.\",\n      \"method\": \"ChIP for H3K4 methylation at Setd5 promoter, Co-IP (ANKRD11–WDR5), rRNA quantification, polysome profiling/translation assay, overexpression rescue\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP, Co-IP, functional rescue; single lab, mechanistic pathway placement via genetic rescue\",\n      \"pmids\": [\"40520101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ANKRD11 loss-of-function variants reduce CDKN1A/p21 promoter-driven luciferase activity; re-introduction of wild-type ANKRD11 but not pathogenic variants (p.Lys1347del or p.Leu2143Val) restores p21 promoter activity and endogenous p21 mRNA levels, confirming the transcriptional activation function of ANKRD11 toward CDKN1A.\",\n      \"method\": \"p21-promoter luciferase reporter assay, RT-PCR for endogenous CDKN1A mRNA, re-expression of wild-type vs. mutant ANKRD11\",\n      \"journal\": \"American journal of medical genetics. Part A\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay with isogenic mutant rescue, single lab, two orthogonal readouts\",\n      \"pmids\": [\"33354850\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A truncating frameshift ANKRD11 variant (p.Y761Qfs*20) escapes nonsense-mediated mRNA decay and produces a truncated protein that accumulates at higher levels than full-length ANKRD11 and localizes predominantly to the nucleus (unlike wild-type which distributes in both nucleus and cytoplasm); the truncated protein significantly reduces CDKN1A/p21-promoter luciferase activity and endogenous p21 mRNA, consistent with dominant-negative loss of transcriptional activation.\",\n      \"method\": \"NMD escape assay, immunofluorescence localization, p21-promoter luciferase reporter assay, RT-PCR, western blot for protein levels\",\n      \"journal\": \"Heliyon\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal cell-based assays, single lab, single variant studied\",\n      \"pmids\": [\"38515699\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The ANKRD11 promoter is specifically methylated at three CpG sites in a 19 bp region in breast tumors compared to normal tissue; treatment of breast cancer cell lines with DNA demethylating agents upregulates ANKRD11 expression, linking promoter methylation to transcriptional silencing of ANKRD11.\",\n      \"method\": \"SEQUENOM Epityper methylation analysis, dual-luciferase reporter assay for promoter activity, demethylating agent treatment with expression measurement\",\n      \"journal\": \"European journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative methylation mapping, luciferase reporter, pharmacological demethylation rescue; single lab\",\n      \"pmids\": [\"22538187\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANKRD11 is a large nuclear chromatin regulator that controls gene expression by (1) acting as a p53 coactivator through association with acetyltransferases P/CAF and hADA3 to enhance p53 acetylation and CDKN1A transcription, (2) modulating histone acetylation via HDAC3, with which it forms a complex that also recruits the minor spliceosomal factor 65K/RNPC3 to co-regulate chromatin deacetylation, (3) binding the cohesin complex through an N-terminal peptide to compete with CTCF and regulate developmental gene expression, (4) promoting SETD5 expression via WDR5/H3K4 methylation to sustain rRNA production and translation, and (5) suppressing oncogenic mutant p53 by restoring its native conformation and disrupting mutant p53–p63 complexes; nuclear localization depends on a bipartite NLS (residues 53–87) that binds Importin α1, protein abundance is regulated by C-terminal D-box-mediated proteasomal degradation, and in vivo loss-of-function in neural crest cells causes craniofacial, skeletal, palatal, and cardiac outflow tract defects, while in neurons it governs histone acetylation-dependent dendrite growth and migration through the BDNF/TrkB pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ANKRD11 is a large nuclear chromatin regulator that controls developmental gene expression by coupling transcription factors to histone-modifying and chromatin-architecture machinery [#3, #7, #13]. It functions as a p53 coactivator, physically associating with p53 and the acetyltransferases P/CAF and hADA3 to enhance p53 acetylation, p53 occupancy of the CDKN1A promoter, and p21 expression [#1]; loss-of-function and dominant-negative pathogenic variants reduce CDKN1A promoter activity and p21 transcription [#17, #18]. Through its HDAC-binding domain it associates with chromatin and HDAC3 to set histone acetylation levels at target genes during neural development [#3], and it bridges HDAC3 with the minor spliceosomal protein 65K/RNPC3 to drive their co-occupancy and H3K9 deacetylation at shared loci [#12]. ANKRD11 also acts as a broad enhancer repressor, recruited by AIB1 to TEAD-bound sites to restrain YAP-activated transcription, and its loss globally elevates H3K27 acetylation at oncogenic enhancers [#7, #10]. Independently, a short N-terminal peptide binds the cohesin complex and competes with CTCF, linking ANKRD11 to genome architecture, while at the Setd5 promoter it recruits WDR5 to deposit H3K4 methylation and sustain rRNA production and translation [#13, #16]. Nuclear import depends on a bipartite NLS (residues 53–87) that binds Importin α1, and protein abundance is controlled by C-terminal proteasomal degradation signals [#14, #4]. In vivo, loss of Ankrd11 in neural crest cells produces craniofacial, palatal, skeletal, and cardiac outflow-tract defects, and in cortical neurons it governs histone-acetylation-dependent dendrite growth and radial migration via the BDNF/TrkB pathway [#8, #15, #5]; pathogenic ANKRD11 variants cause KBG syndrome through reduced protein stability or impaired transcriptional repression [#11, #14].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established Ankrd11 as a genetic regulator of skeletal and craniofacial development in vivo, before any molecular mechanism was known.\",\n      \"evidence\": \"ENU mutagenesis screen and positional cloning of the Yoda missense mouse with bone density and skull phenotypes\",\n      \"pmids\": [\"17986521\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular pathway downstream of bone regulation not defined\", \"Homozygous lethality precluded analysis of full loss of function\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defined a first molecular function — that ANKRD11 coactivates p53-dependent transcription — by linking it to acetyltransferases and a defined transcriptional readout.\",\n      \"evidence\": \"Reciprocal Co-IP with p53/P/CAF/hADA3, ChIP at CDKN1A, shRNA knockdown, acetyl-p53 western blot\",\n      \"pmids\": [\"18840648\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct enzymatic versus scaffolding contribution to acetylation not separated\", \"Structural basis of p53/P/CAF binding unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Extended the p53 link to oncogenic mutant p53, showing ANKRD11 can restore native conformation and dissociate mutant p53–p63 complexes to suppress malignant phenotypes.\",\n      \"evidence\": \"Inducible expression, conformational antibody and Co-IP assays, invasion and centrosome/mitosis analysis\",\n      \"pmids\": [\"21986947\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of conformational restoration not biochemically resolved\", \"Single-lab cellular study\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed ANKRD11 is predominantly nuclear in neurons and redistributes into nuclear inclusions on depolarization, hinting at activity-dependent regulation relevant to neural plasticity.\",\n      \"evidence\": \"Direct imaging and depolarization in neurons\",\n      \"pmids\": [\"21782149\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional significance of nuclear inclusions not established\", \"Single method, single lab\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linked ANKRD11 silencing to cancer by showing its promoter is methylated in breast tumors and reactivated by demethylation.\",\n      \"evidence\": \"Epityper methylation mapping, luciferase promoter assay, demethylating-agent treatment\",\n      \"pmids\": [\"22538187\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal role of silencing in tumorigenesis not tested\", \"Downstream consequences of loss not addressed in this study\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified the chromatin/HDAC3 axis as ANKRD11's developmental mechanism, with genetic epistasis showing histone acetylation control drives neural precursor proliferation.\",\n      \"evidence\": \"Chromatin association, HDAC3 co-localization, Yoda HDAC-binding-domain point mutant, rescue by HDAC3 or HAT inhibition\",\n      \"pmids\": [\"25556659\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct target gene set incompletely defined\", \"How ANKRD11 selects loci not resolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined how ANKRD11 abundance is controlled, attributing pathogenic accumulation to disruption of C-terminal D-box degradation signals.\",\n      \"evidence\": \"Cell-cycle protein abundance analysis, in silico D-box identification, analysis of 11 pathogenic variants\",\n      \"pmids\": [\"25413698\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro reconstitution of proteasomal degradation\", \"Responsible E3 ligase not identified\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed ANKRD11 in a neuronal epigenetic circuit, showing it maintains acetylated H3/p53 at the TrkB promoter to drive BDNF/TrkB-dependent migration and dendrite growth.\",\n      \"evidence\": \"In utero electroporation knockdown, ChIP for acetylation and MeCP2/DNMT1 occupancy, TrkB overexpression rescue\",\n      \"pmids\": [\"29274743\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct versus indirect occupancy of the TrkB promoter not separated\", \"Link to human neurodevelopmental phenotypes inferred from mouse\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed a repressive chromatin function: ANKRD11/ANCO1 is recruited by AIB1 to TEAD sites to repress YAP-activated genes and restrain aberrant growth.\",\n      \"evidence\": \"Sequential ChIP, ChIP-seq, knockdown, 3D growth assay in breast epithelial cells\",\n      \"pmids\": [\"31788936\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of repression at TEAD sites not defined\", \"Relationship to HDAC3-based repression not integrated\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Confirmed clinically that pathogenic ANKRD11 variants abolish its CDKN1A transcriptional activation, validating the p53/p21 readout as disease-relevant.\",\n      \"evidence\": \"p21-promoter luciferase and endogenous p21 RT-PCR with wild-type versus mutant re-expression\",\n      \"pmids\": [\"33354850\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Only two variants tested\", \"In vivo consequence of impaired p21 activation not shown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated a cell-autonomous requirement for Ankrd11 in neural crest for craniofacial bone and palate formation, with reduced precursor proliferation.\",\n      \"evidence\": \"Neural crest-specific conditional knockout, micro-CT, histology, BrdU/EdU proliferation assays\",\n      \"pmids\": [\"33996804\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular targets mediating the proliferation defect not identified\", \"Chromatin mechanism not directly tested in this model\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Resolved the genotype–mechanism relationship for KBG syndrome, showing missense variants act by either reduced stability or impaired repression and cluster in C-terminal repression domain 2.\",\n      \"evidence\": \"Cell-based stability and transcriptional-repression assays for 10 variants, variant clustering analysis\",\n      \"pmids\": [\"35833929\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Two mechanisms not linked to distinct clinical outcomes\", \"Single-lab functional assays\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapped the nuclear import determinant, identifying a bipartite NLS that binds Importin α1 and is required for endogenous nuclear localization.\",\n      \"evidence\": \"Site-directed mutagenesis, GFP nuclear-import assay, Importin α1 binding, immunofluorescence in HeLa\",\n      \"pmids\": [\"37290286\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regulation of import not addressed\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Connected ANKRD11–HDAC3 activation to therapy resistance, showing a SERPINA3–ANKRD11–HDAC3 axis drives aromatase inhibitor resistance.\",\n      \"evidence\": \"Co-IP, HDAC3 activity assay, knockdown/overexpression, drug resistance assays\",\n      \"pmids\": [\"37414914\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How ANKRD11 binding stimulates HDAC3 activity not defined\", \"Single-lab cancer model\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined ANKRD11/ANCO1 as a broad enhancer repressor, with loss elevating H3K27Ac at oncogenic enhancers enriched for AP-1, TEAD, STAT3 and NFκB motifs.\",\n      \"evidence\": \"H3K27Ac ChIP-seq in ANCO1-depleted TNBC cells, 3D invasion, xenograft\",\n      \"pmids\": [\"37511268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct recruitment mechanism to each enhancer class unresolved\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established ANKRD11 as a conserved bridging factor coupling HDAC3 to the minor spliceosomal protein 65K/RNPC3 for chromatin co-occupancy and H3K9 deacetylation.\",\n      \"evidence\": \"Affinity purification in Drosophila, CRISPR deletions, Co-IP and CUT&Tag in human cells, domain mapping\",\n      \"pmids\": [\"38837887\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of linking splicing factor to chromatin deacetylation unclear\", \"Target gene network incompletely defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed a truncating frameshift variant escapes NMD, over-accumulates as a nuclear-restricted protein, and dominant-negatively impairs p21 activation.\",\n      \"evidence\": \"NMD escape assay, localization, p21 luciferase, RT-PCR, western blot\",\n      \"pmids\": [\"38515699\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single variant studied\", \"Dominant-negative mechanism inferred, not structurally shown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended the neural crest requirement to the heart, showing Ankrd11 controls cardiac outflow tract septation through transcription/chromatin and mTOR/BMP/TGF-β programs.\",\n      \"evidence\": \"Neural crest conditional knockout, echocardiography, histology, cardiac neural crest transcriptomics\",\n      \"pmids\": [\"38951500\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct ANKRD11 targets in cardiac neural crest not pinpointed\", \"Connection to specific chromatin complexes not tested in this model\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Provided structural and genetic proof that ANKRD11 binds cohesin via an N-terminal peptide and competes with CTCF, with a single Y347A mutation perturbing gene expression and causing developmental anomalies.\",\n      \"evidence\": \"Crystal structure, biochemical binding/competition, Y347A knock-in mouse, mESC expression analysis\",\n      \"pmids\": [\"39847329\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide map of ANKRD11-dependent cohesin/CTCF sites not reported\", \"Relationship between cohesin binding and HDAC3/repression functions not integrated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified a ribosome-biogenesis function in which ANKRD11 recruits WDR5 to the Setd5 promoter to drive H3K4 methylation, SETD5 expression, rRNA production and translation.\",\n      \"evidence\": \"ChIP for H3K4me at Setd5, ANKRD11–WDR5 Co-IP, rRNA quantification, polysome profiling, rescue\",\n      \"pmids\": [\"40520101\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus scaffolded WDR5 recruitment not resolved\", \"Tissue specificity of this axis not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ANKRD11's distinct activities — p53 coactivation, HDAC3/65K-mediated deacetylation, WDR5/H3K4 activation, ANCO1 enhancer repression, and cohesin/CTCF competition — are coordinated at the genome and which dominate in each developmental context remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model integrating activating and repressive chromatin functions\", \"No single study mapping all ANKRD11 partners on shared loci\", \"Domain-level partitioning of the multiple interactions only partially mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 7, 10, 17]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [12, 16, 1]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1, 7, 13]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [3, 12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 14, 18]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [3, 12, 13]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [3, 10, 12, 13]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 7, 16, 17]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [8, 15, 5, 6]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [16]}\n    ],\n    \"complexes\": [\n      \"cohesin complex\",\n      \"ANKRD11–HDAC3–65K/RNPC3 complex\"\n    ],\n    \"partners\": [\n      \"TP53\",\n      \"PCAF\",\n      \"TADA3\",\n      \"HDAC3\",\n      \"RNPC3\",\n      \"WDR5\",\n      \"NCOA3\",\n      \"KPNA\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}