{"gene":"ANKS1B","run_date":"2026-04-28T17:12:37","timeline":{"discoveries":[{"year":2004,"finding":"AIDA-1 proteins (isoforms AIDA-1a, AIDA-1b, AIDA-1bΔAnk) interact with the amyloid precursor protein (AbetaPP) intracellular domain in vitro, in living cells, and endogenously in leukemia cell lines; overexpression of AbetaPP alters the intracellular distribution of AIDA-1a, and different isoforms localize to distinct subcellular compartments.","method":"Co-immunoprecipitation, in vitro binding assay, transfection/overexpression with confocal imaging","journal":"Journal of Alzheimer's disease : JAD","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP in multiple systems, single lab","pmids":["15004329"],"is_preprint":false},{"year":2005,"finding":"A novel ANKS1B/EB-1 isoform, AIDA-1c, interacts with the Cajal body marker protein coilin and competes with SmB' for coilin binding sites but does not bind SMN; knockdown of EB-1/AIDA-1 isoforms by siRNA alters Cajal body organization and reduces cell viability.","method":"Co-immunoprecipitation, competition binding assay, siRNA knockdown, fluorescence microscopy","journal":"BMC cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple binding assays and KD phenotype, single lab","pmids":["15862129"],"is_preprint":false},{"year":2007,"finding":"AIDA-1d is a postsynaptic density component that binds the first two PDZ domains of PSD-95 via its C-terminal three amino acids; NMDA receptor stimulation induces Ca2+-independent translocation of AIDA-1d to the nucleus where it couples to Cajal bodies and induces Cajal body-nucleolar association, leading to increased nucleolar numbers and protein synthesis.","method":"Co-immunoprecipitation, live-cell imaging, NMDA stimulation, siRNA knockdown with protein synthesis assay","journal":"Nature neuroscience","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (biochemistry, imaging, functional assay), replicated across conditions","pmids":["17334360"],"is_preprint":false},{"year":2009,"finding":"NMR structure of the tandem SAM domain of AIDA-1 reveals a head-to-tail orientation with the nuclear localization signal buried at the SAM-SAM domain interface; differential thermal stability of the two SAM domains suggests a mechanism whereby the second SAM domain decouples from the first to expose the NLS and facilitate nuclear import.","method":"NMR structure determination, thermal stability assay","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 — NMR structure with mechanistic functional interpretation","pmids":["19666031"],"is_preprint":false},{"year":2015,"finding":"AIDA-1 preferentially associates with GluN2B and with CASK and KIF17 (adaptors regulating GluN2B-containing NMDAR transport from ER to synapses); conditional forebrain knockout of AIDA-1 reduces GluN2B-mediated and increases GluN2A-mediated synaptic transmission, with GluN2B accumulating in ER-enriched fractions, indicating AIDA-1 facilitates ER-to-synapse transport of GluN2B.","method":"Conditional knockout, co-immunoprecipitation, subcellular fractionation, electrophysiology, lentiviral shRNA knockdown, immunocytochemistry","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (KO, biochemistry, electrophysiology, imaging), strong mechanistic evidence","pmids":["26085624"],"is_preprint":false},{"year":2015,"finding":"Under basal conditions, AIDA-1 is located within the dense core of the PSD (~30 nm from postsynaptic membrane); under excitatory conditions (high K+ or NMDA), AIDA-1 label density at the PSD core is reduced to 40% of controls and median distance increases to ~55 nm, with the effect reversible within 30 minutes.","method":"Immunogold electron microscopy with two distinct antibodies in cultured hippocampal neurons","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization with functional context using two antibodies, single lab","pmids":["26356309"],"is_preprint":false},{"year":2015,"finding":"ANKS1B was identified as a novel binding partner of KRIT1 (CCM1) by yeast two-hybrid screen; silencing of ANKS1B in primary human endothelial cells increases permeability, and forced ANKS1B expression reduces permeability, independently of Rho kinase activity and KRIT1 presence.","method":"Yeast two-hybrid screen, siRNA knockdown, overexpression, endothelial permeability assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 — binding identified by Y2H, functional phenotype by KD/OE, single lab","pmids":["26698571"],"is_preprint":false},{"year":2016,"finding":"CaMKII activation phosphorylates AIDA-1 in PSD fractions from brain, and NMDA treatment causes an ~30 nm shift in AIDA-1 median distance from the postsynaptic membrane in hippocampal neurons; this redistribution is blocked by the CaMKII inhibitor tatCN21, establishing CaMKII-mediated phosphorylation as the mechanism for activity-induced displacement of AIDA-1 from the PSD core.","method":"Biochemical phosphorylation assay of PSD fractions, immuno-electron microscopy, CaMKII inhibitor treatment","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 2 — biochemical phosphorylation assay plus immuno-EM with pharmacological inhibition, multiple orthogonal methods","pmids":["27477489"],"is_preprint":false},{"year":2019,"finding":"Quantitative proteomics of the AIDA-1 interactome in neurons identifies protein networks involved in synaptic function; haploinsufficiency of ANKS1B in a transgenic mouse model recapitulates social deficits, hyperactivity, and sensorimotor dysfunction, demonstrating AIDA-1 loss-of-function drives specific neurodevelopmental phenotypes.","method":"Quantitative mass spectrometry-based proteomics (interactome), transgenic mouse model with behavioral analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — MS-based interactome plus in vivo KO with defined phenotypes, multiple orthogonal methods","pmids":["31388001"],"is_preprint":false},{"year":2023,"finding":"Anks1b-deficient mice display deficits in oligodendrocyte maturation, myelination, and Rac1 function; selective loss of Anks1b from the oligodendrocyte lineage (but not from neurons) recapitulates social preference and sensory reactivity deficits, and clemastine rescues social deficits in these mice, establishing an oligodendroglial role for AIDA-1 mediated by Rac1 activity.","method":"Conditional cell-type-specific knockout, MRI white matter imaging, oligodendrocyte maturation assays, Rac1 activity assay, pharmacological rescue","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — cell-type-specific KO with epistatic rescue and multiple mechanistic readouts, strong evidence","pmids":["38129387"],"is_preprint":false},{"year":2024,"finding":"The PTB domain of AIDA-1 binds to an extended NPx[F/Y]-motif of SynGAP family Ras-GTPase activating proteins with high affinity; crystal structure of the AIDA-1 PTB domain in complex with the SynGAP NPxF-motif reveals the molecular basis for this specific interaction.","method":"Affinity purification, biochemical binding assay, X-ray crystallography","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 — crystal structure plus biochemical binding characterization","pmids":["38759928"],"is_preprint":false},{"year":2026,"finding":"Ischemia induces lactylation of ANKS1B at K1222, targeting it for ubiquitin-proteasome-mediated degradation; loss of ANKS1B causes GluN2B retention in the ER, while a lactylation-resistant mutant (K1222R) restores GluN2B surface trafficking but exacerbates Ca2+ overload and neuronal death, indicating lactylation-driven ANKS1B degradation is a neuroprotective feedback mechanism limiting excitotoxicity.","method":"Proteomics, OGD/R cell model, ubiquitin-proteasome pathway assay, site-directed mutagenesis (K1222R), Ca2+ imaging, surface trafficking assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — mutagenesis plus functional trafficking and cell death assays, single lab","pmids":["41564684"],"is_preprint":false}],"current_model":"ANKS1B encodes AIDA-1, a postsynaptic scaffold protein whose PTB domain binds NPxF-motifs of SynGAP family proteins and whose C-terminus anchors it to PSD-95; CaMKII-mediated phosphorylation displaces AIDA-1 from the PSD core upon synaptic activity, releasing it to translocate to the nucleus (facilitated by SAM-domain uncoupling that exposes a buried NLS) where it regulates nucleolar assembly and protein synthesis; at synapses, AIDA-1 facilitates ER-to-synapse trafficking of GluN2B-containing NMDARs via association with CASK and KIF17, thereby controlling NMDAR subunit composition and plasticity; in oligodendrocytes, AIDA-1 regulates Rac1 activity to control myelination; and in ischemia, lactylation at K1222 targets ANKS1B for proteasomal degradation as a neuroprotective brake on GluN2B surface expression."},"narrative":{"teleology":[{"year":2004,"claim":"Identification of AIDA-1 as an intracellular binding partner of amyloid precursor protein established the gene product as a multi-isoform PTB-domain protein with isoform-specific subcellular distributions.","evidence":"Co-immunoprecipitation and in vitro binding in leukemia cell lines and transfected cells","pmids":["15004329"],"confidence":"Medium","gaps":["Physiological significance of APP interaction in neurons not demonstrated","No in vivo validation"]},{"year":2005,"claim":"Discovery that the AIDA-1c isoform binds the Cajal body marker coilin and competes with SmB' for coilin binding revealed a nuclear role for ANKS1B in snRNP body organization, with knockdown altering Cajal body integrity and reducing cell viability.","evidence":"Co-immunoprecipitation, competition binding, siRNA knockdown with fluorescence microscopy","pmids":["15862129"],"confidence":"Medium","gaps":["Mechanism by which AIDA-1c reaches the nucleus was unknown","Cajal body phenotype not confirmed in neurons"]},{"year":2007,"claim":"Demonstration that AIDA-1d resides in the PSD via PSD-95 binding and translocates to the nucleus upon NMDA stimulation — where it drives Cajal body–nucleolar association and increases protein synthesis — established the first activity-dependent synapse-to-nucleus signaling function for this protein.","evidence":"Co-IP, live-cell imaging, NMDA stimulation, siRNA knockdown with protein synthesis assay in cultured neurons","pmids":["17334360"],"confidence":"High","gaps":["Ca²⁺-independent translocation mechanism was not resolved","In vivo relevance of nucleolar regulation not tested"]},{"year":2009,"claim":"NMR structure of the tandem SAM domains revealed that the NLS is buried at the SAM–SAM interface and that differential thermal stability of the two domains provides a structural mechanism for NLS exposure, explaining how AIDA-1 can switch between synaptic retention and nuclear import.","evidence":"NMR structure determination and thermal stability analysis","pmids":["19666031"],"confidence":"High","gaps":["No direct demonstration that SAM uncoupling occurs in living neurons upon stimulation","Upstream signal triggering SAM uncoupling not identified"]},{"year":2015,"claim":"Conditional forebrain knockout and biochemical studies showed AIDA-1 associates with CASK and KIF17 to facilitate ER-to-synapse transport of GluN2B-containing NMDARs; loss of AIDA-1 shifted synaptic NMDAR composition from GluN2B- to GluN2A-mediated transmission, defining AIDA-1 as a key determinant of NMDAR subunit composition.","evidence":"Conditional knockout, co-IP, subcellular fractionation, electrophysiology, shRNA knockdown in cultured neurons","pmids":["26085624"],"confidence":"High","gaps":["Direct interaction surface between AIDA-1 and CASK/KIF17 not mapped","Whether AIDA-1 rides with the transport vesicle or acts at the ER exit site was unclear"]},{"year":2015,"claim":"Immuno-electron microscopy placed AIDA-1 within the PSD dense core (~30 nm from the membrane) under basal conditions and showed reversible activity-dependent redistribution to ~55 nm, providing ultrastructural evidence for stimulus-driven PSD reorganization of this scaffold.","evidence":"Immunogold EM with two distinct antibodies in cultured hippocampal neurons","pmids":["26356309"],"confidence":"Medium","gaps":["The kinase responsible for the displacement was not yet identified","Nuclear translocation was not tracked at the EM level"]},{"year":2016,"claim":"Identification of CaMKII as the kinase that phosphorylates AIDA-1 in PSD fractions, with pharmacological inhibition blocking activity-induced displacement, resolved the signaling mechanism coupling synaptic activity to AIDA-1 release from the PSD core.","evidence":"Biochemical phosphorylation assay of brain PSD fractions, immuno-EM with CaMKII inhibitor tatCN21","pmids":["27477489"],"confidence":"High","gaps":["Specific phosphorylation site(s) on AIDA-1 not identified","Whether phosphorylation is necessary for nuclear translocation versus merely PSD release was not tested"]},{"year":2019,"claim":"Haploinsufficiency in mice reproduced social deficits, hyperactivity, and sensorimotor dysfunction, and quantitative interactome profiling placed AIDA-1 at the hub of synaptic protein networks, establishing ANKS1B as a neurodevelopmental disease gene.","evidence":"Quantitative MS-based interactome in neurons, heterozygous knockout mouse with behavioral phenotyping","pmids":["31388001"],"confidence":"High","gaps":["Specific interactors driving each behavioral phenotype not dissected","Human genetic validation for neurodevelopmental disorder not shown in this study"]},{"year":2023,"claim":"Cell-type-specific knockout from the oligodendrocyte lineage — but not neurons — recapitulated social and sensory deficits, and these were rescued by clemastine, revealing a previously unsuspected oligodendroglial function of AIDA-1 mediated by Rac1 activity control of myelination.","evidence":"Conditional oligodendrocyte-lineage knockout, MRI white matter imaging, Rac1 activity assay, pharmacological rescue with clemastine","pmids":["38129387"],"confidence":"High","gaps":["Direct molecular link between AIDA-1 and Rac1 activation not defined","Whether neuronal and oligodendroglial AIDA-1 functions are independent or synergistic in vivo is unclear"]},{"year":2024,"claim":"Crystal structure of the AIDA-1 PTB domain bound to the SynGAP NPxF motif provided the atomic-resolution basis for how AIDA-1 recognizes and anchors SynGAP family Ras-GAPs at the PSD.","evidence":"X-ray crystallography, affinity purification, and biochemical binding assays","pmids":["38759928"],"confidence":"High","gaps":["Functional consequence of disrupting the AIDA-1–SynGAP interaction on synaptic Ras signaling not tested in neurons","Whether other PTB-binding partners compete with SynGAP at the PSD is unknown"]},{"year":2026,"claim":"Discovery that ischemia-induced lactylation at K1222 triggers ubiquitin-proteasome-mediated AIDA-1 degradation, causing GluN2B ER retention, established a metabolic post-translational mechanism that limits excitotoxicity by reducing surface NMDAR expression.","evidence":"OGD/R cell model, proteomics, K1222R mutagenesis, Ca²⁺ imaging, surface trafficking assay","pmids":["41564684"],"confidence":"Medium","gaps":["Lactylation-driven degradation not validated in vivo in ischemia models","The E3 ubiquitin ligase mediating AIDA-1 ubiquitination is unidentified","Single lab finding"]},{"year":null,"claim":"Key unresolved questions include the specific CaMKII phosphorylation site(s) on AIDA-1, whether SAM-domain uncoupling is triggered by phosphorylation or an independent signal, the molecular basis of AIDA-1's regulation of Rac1 in oligodendrocytes, and how the PTB-mediated SynGAP interaction coordinates with GluN2B trafficking functions.","evidence":"","pmids":[],"confidence":"Low","gaps":["CaMKII phosphorylation site(s) unmapped","SAM uncoupling trigger unresolved","AIDA-1–Rac1 mechanism in oligodendrocytes undefined","No integrative structural model of full-length AIDA-1 in the PSD"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,4,10]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,5,8]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,2,3]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[2]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2,5,7]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[4,11]}],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[2,4,5,7,8,10]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[7,9,11]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[4,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[8,9]}],"complexes":["PSD-95/AIDA-1 postsynaptic complex"],"partners":["DLG4","SYNGAP1","CASK","KIF17","GRIN2B","COIL","KRIT1"],"other_free_text":[]},"mechanistic_narrative":"ANKS1B encodes AIDA-1, a multidomain postsynaptic scaffold protein that orchestrates NMDA receptor trafficking, synaptic signaling, and nuclear functions in neurons and oligodendrocytes. At synapses, AIDA-1 anchors to PSD-95 via its C-terminus and binds SynGAP family proteins through its PTB domain; it facilitates ER-to-synapse transport of GluN2B-containing NMDARs through association with CASK and KIF17, and CaMKII-mediated phosphorylation displaces AIDA-1 from the PSD core upon synaptic activity, enabling its translocation to the nucleus where SAM-domain uncoupling exposes a buried NLS and AIDA-1 promotes nucleolar assembly and protein synthesis [PMID:26085624, PMID:27477489, PMID:17334360, PMID:19666031, PMID:38759928]. In oligodendrocytes, AIDA-1 regulates Rac1 activity to control myelination and maturation, and cell-type-specific loss from the oligodendrocyte lineage causes social and sensory deficits rescuable by clemastine [PMID:38129387]. Haploinsufficiency of ANKS1B in mice produces neurodevelopmental phenotypes including social deficits and hyperactivity, and under ischemic conditions, lactylation at K1222 targets AIDA-1 for proteasomal degradation as a neuroprotective brake on GluN2B surface expression and excitotoxic calcium overload [PMID:31388001, PMID:41564684]."},"prefetch_data":{"uniprot":{"accession":"Q7Z6G8","full_name":"Ankyrin repeat and sterile alpha motif domain-containing protein 1B","aliases":["Amyloid-beta protein intracellular domain-associated protein 1","AIDA-1","E2A-PBX1-associated protein","EB-1"],"length_aa":1248,"mass_kda":138.1,"function":"Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells Isoform 3 can regulate global protein synthesis by altering nucleolar numbers Isoform 4 may play a role as a modulator of APP processing. Overexpression can down-regulate APP processing","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q7Z6G8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ANKS1B","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ANKS1B","total_profiled":1310},"omim":[{"mim_id":"607815","title":"ANKYRIN REPEAT AND STERILE ALPHA MOTIF DOMAINS-CONTAINING PROTEIN 1B; ANKS1B","url":"https://www.omim.org/entry/607815"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Plasma membrane","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":66.3}],"url":"https://www.proteinatlas.org/search/ANKS1B"},"hgnc":{"alias_symbol":["EB-1","AIDA-1","cajalin-2","ANKS2"],"prev_symbol":[]},"alphafold":{"accession":"Q7Z6G8","domains":[{"cath_id":"1.25.40.20","chopping":"214-288","consensus_level":"medium","plddt":87.9396,"start":214,"end":288},{"cath_id":"1.10.150.50","chopping":"814-876","consensus_level":"medium","plddt":84.3648,"start":814,"end":876},{"cath_id":"1.10.150.50","chopping":"880-946","consensus_level":"medium","plddt":81.2381,"start":880,"end":946},{"cath_id":"2.30.29.30","chopping":"1052-1192","consensus_level":"high","plddt":86.6952,"start":1052,"end":1192}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z6G8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z6G8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z6G8-F1-predicted_aligned_error_v6.png","plddt_mean":56.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ANKS1B","jax_strain_url":"https://www.jax.org/strain/search?query=ANKS1B"},"sequence":{"accession":"Q7Z6G8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z6G8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z6G8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z6G8"}},"corpus_meta":[{"pmid":"9348288","id":"PMC_9348288","title":"Mal3, the fission yeast homologue of the human APC-interacting protein EB-1 is required for microtubule integrity and the maintenance of cell form.","date":"1997","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9348288","citation_count":191,"is_preprint":false},{"pmid":"17334360","id":"PMC_17334360","title":"Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons.","date":"2007","source":"Nature neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/17334360","citation_count":96,"is_preprint":false},{"pmid":"24479813","id":"PMC_24479813","title":"ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.","date":"2014","source":"BMC urology","url":"https://pubmed.ncbi.nlm.nih.gov/24479813","citation_count":50,"is_preprint":false},{"pmid":"15082872","id":"PMC_15082872","title":"The anxiolytic-like activity of AIDA (1-aminoindan-1,5-dicarboxylic acid), an mGLu 1 receptor antagonist.","date":"2004","source":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society","url":"https://pubmed.ncbi.nlm.nih.gov/15082872","citation_count":37,"is_preprint":false},{"pmid":"28468915","id":"PMC_28468915","title":"Combining DNA Vaccine and AIDA-1 in Attenuated Salmonella Activates Tumor-Specific CD4+ and CD8+ T-cell Responses.","date":"2017","source":"Cancer immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/28468915","citation_count":35,"is_preprint":false},{"pmid":"26085624","id":"PMC_26085624","title":"ANKS1B Gene Product AIDA-1 Controls Hippocampal Synaptic Transmission by Regulating GluN2B Subunit Localization.","date":"2015","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/26085624","citation_count":34,"is_preprint":false},{"pmid":"19666031","id":"PMC_19666031","title":"A nuclear localization signal at the SAM-SAM domain interface of AIDA-1 suggests a requirement for domain uncoupling prior to nuclear import.","date":"2009","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19666031","citation_count":32,"is_preprint":false},{"pmid":"15004329","id":"PMC_15004329","title":"The intracellular localization of amyloid beta protein precursor (AbetaPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AbetaPP and alternative splicing.","date":"2004","source":"Journal of Alzheimer's disease : JAD","url":"https://pubmed.ncbi.nlm.nih.gov/15004329","citation_count":31,"is_preprint":false},{"pmid":"31388001","id":"PMC_31388001","title":"Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31388001","citation_count":28,"is_preprint":false},{"pmid":"16769578","id":"PMC_16769578","title":"The effects of siRNA-mediated inhibition of E2A-PBX1 on EB-1 and Wnt16b expression in the 697 pre-B leukemia cell line.","date":"2006","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/16769578","citation_count":27,"is_preprint":false},{"pmid":"10490826","id":"PMC_10490826","title":"EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1.","date":"1999","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/10490826","citation_count":25,"is_preprint":false},{"pmid":"15862129","id":"PMC_15862129","title":"A novel EB-1/AIDA-1 isoform, AIDA-1c, interacts with the Cajal body protein coilin.","date":"2005","source":"BMC cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15862129","citation_count":17,"is_preprint":false},{"pmid":"11831388","id":"PMC_11831388","title":"EB 1 immunofluorescence reveals an increase in growing astral microtubule length and number during anaphase in NRK-52E cells.","date":"2001","source":"European journal of cell 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biology","url":"https://pubmed.ncbi.nlm.nih.gov/38759928","citation_count":2,"is_preprint":false},{"pmid":"37597021","id":"PMC_37597021","title":"Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells.","date":"2023","source":"Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology","url":"https://pubmed.ncbi.nlm.nih.gov/37597021","citation_count":2,"is_preprint":false},{"pmid":"41564684","id":"PMC_41564684","title":"Lactylation-mediated degradation of ANKS1B mitigates ischemic excitotoxicity by impairing GluN2B trafficking.","date":"2026","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/41564684","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13409,"output_tokens":2991,"usd":0.042546},"stage2":{"model":"claude-opus-4-6","input_tokens":6338,"output_tokens":3113,"usd":0.164272},"total_usd":0.206818,"stage1_batch_id":"msgbatch_01TqNM6p6FsoMBT2jzQTwKBr","stage2_batch_id":"msgbatch_01Ya473eco8sTHbvRymQaU8o","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"AIDA-1 proteins (isoforms AIDA-1a, AIDA-1b, AIDA-1bΔAnk) interact with the amyloid precursor protein (AbetaPP) intracellular domain in vitro, in living cells, and endogenously in leukemia cell lines; overexpression of AbetaPP alters the intracellular distribution of AIDA-1a, and different isoforms localize to distinct subcellular compartments.\",\n      \"method\": \"Co-immunoprecipitation, in vitro binding assay, transfection/overexpression with confocal imaging\",\n      \"journal\": \"Journal of Alzheimer's disease : JAD\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP in multiple systems, single lab\",\n      \"pmids\": [\"15004329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"A novel ANKS1B/EB-1 isoform, AIDA-1c, interacts with the Cajal body marker protein coilin and competes with SmB' for coilin binding sites but does not bind SMN; knockdown of EB-1/AIDA-1 isoforms by siRNA alters Cajal body organization and reduces cell viability.\",\n      \"method\": \"Co-immunoprecipitation, competition binding assay, siRNA knockdown, fluorescence microscopy\",\n      \"journal\": \"BMC cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple binding assays and KD phenotype, single lab\",\n      \"pmids\": [\"15862129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"AIDA-1d is a postsynaptic density component that binds the first two PDZ domains of PSD-95 via its C-terminal three amino acids; NMDA receptor stimulation induces Ca2+-independent translocation of AIDA-1d to the nucleus where it couples to Cajal bodies and induces Cajal body-nucleolar association, leading to increased nucleolar numbers and protein synthesis.\",\n      \"method\": \"Co-immunoprecipitation, live-cell imaging, NMDA stimulation, siRNA knockdown with protein synthesis assay\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (biochemistry, imaging, functional assay), replicated across conditions\",\n      \"pmids\": [\"17334360\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"NMR structure of the tandem SAM domain of AIDA-1 reveals a head-to-tail orientation with the nuclear localization signal buried at the SAM-SAM domain interface; differential thermal stability of the two SAM domains suggests a mechanism whereby the second SAM domain decouples from the first to expose the NLS and facilitate nuclear import.\",\n      \"method\": \"NMR structure determination, thermal stability assay\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — NMR structure with mechanistic functional interpretation\",\n      \"pmids\": [\"19666031\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"AIDA-1 preferentially associates with GluN2B and with CASK and KIF17 (adaptors regulating GluN2B-containing NMDAR transport from ER to synapses); conditional forebrain knockout of AIDA-1 reduces GluN2B-mediated and increases GluN2A-mediated synaptic transmission, with GluN2B accumulating in ER-enriched fractions, indicating AIDA-1 facilitates ER-to-synapse transport of GluN2B.\",\n      \"method\": \"Conditional knockout, co-immunoprecipitation, subcellular fractionation, electrophysiology, lentiviral shRNA knockdown, immunocytochemistry\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (KO, biochemistry, electrophysiology, imaging), strong mechanistic evidence\",\n      \"pmids\": [\"26085624\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Under basal conditions, AIDA-1 is located within the dense core of the PSD (~30 nm from postsynaptic membrane); under excitatory conditions (high K+ or NMDA), AIDA-1 label density at the PSD core is reduced to 40% of controls and median distance increases to ~55 nm, with the effect reversible within 30 minutes.\",\n      \"method\": \"Immunogold electron microscopy with two distinct antibodies in cultured hippocampal neurons\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization with functional context using two antibodies, single lab\",\n      \"pmids\": [\"26356309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"ANKS1B was identified as a novel binding partner of KRIT1 (CCM1) by yeast two-hybrid screen; silencing of ANKS1B in primary human endothelial cells increases permeability, and forced ANKS1B expression reduces permeability, independently of Rho kinase activity and KRIT1 presence.\",\n      \"method\": \"Yeast two-hybrid screen, siRNA knockdown, overexpression, endothelial permeability assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — binding identified by Y2H, functional phenotype by KD/OE, single lab\",\n      \"pmids\": [\"26698571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CaMKII activation phosphorylates AIDA-1 in PSD fractions from brain, and NMDA treatment causes an ~30 nm shift in AIDA-1 median distance from the postsynaptic membrane in hippocampal neurons; this redistribution is blocked by the CaMKII inhibitor tatCN21, establishing CaMKII-mediated phosphorylation as the mechanism for activity-induced displacement of AIDA-1 from the PSD core.\",\n      \"method\": \"Biochemical phosphorylation assay of PSD fractions, immuno-electron microscopy, CaMKII inhibitor treatment\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — biochemical phosphorylation assay plus immuno-EM with pharmacological inhibition, multiple orthogonal methods\",\n      \"pmids\": [\"27477489\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Quantitative proteomics of the AIDA-1 interactome in neurons identifies protein networks involved in synaptic function; haploinsufficiency of ANKS1B in a transgenic mouse model recapitulates social deficits, hyperactivity, and sensorimotor dysfunction, demonstrating AIDA-1 loss-of-function drives specific neurodevelopmental phenotypes.\",\n      \"method\": \"Quantitative mass spectrometry-based proteomics (interactome), transgenic mouse model with behavioral analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — MS-based interactome plus in vivo KO with defined phenotypes, multiple orthogonal methods\",\n      \"pmids\": [\"31388001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Anks1b-deficient mice display deficits in oligodendrocyte maturation, myelination, and Rac1 function; selective loss of Anks1b from the oligodendrocyte lineage (but not from neurons) recapitulates social preference and sensory reactivity deficits, and clemastine rescues social deficits in these mice, establishing an oligodendroglial role for AIDA-1 mediated by Rac1 activity.\",\n      \"method\": \"Conditional cell-type-specific knockout, MRI white matter imaging, oligodendrocyte maturation assays, Rac1 activity assay, pharmacological rescue\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — cell-type-specific KO with epistatic rescue and multiple mechanistic readouts, strong evidence\",\n      \"pmids\": [\"38129387\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The PTB domain of AIDA-1 binds to an extended NPx[F/Y]-motif of SynGAP family Ras-GTPase activating proteins with high affinity; crystal structure of the AIDA-1 PTB domain in complex with the SynGAP NPxF-motif reveals the molecular basis for this specific interaction.\",\n      \"method\": \"Affinity purification, biochemical binding assay, X-ray crystallography\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure plus biochemical binding characterization\",\n      \"pmids\": [\"38759928\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Ischemia induces lactylation of ANKS1B at K1222, targeting it for ubiquitin-proteasome-mediated degradation; loss of ANKS1B causes GluN2B retention in the ER, while a lactylation-resistant mutant (K1222R) restores GluN2B surface trafficking but exacerbates Ca2+ overload and neuronal death, indicating lactylation-driven ANKS1B degradation is a neuroprotective feedback mechanism limiting excitotoxicity.\",\n      \"method\": \"Proteomics, OGD/R cell model, ubiquitin-proteasome pathway assay, site-directed mutagenesis (K1222R), Ca2+ imaging, surface trafficking assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — mutagenesis plus functional trafficking and cell death assays, single lab\",\n      \"pmids\": [\"41564684\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANKS1B encodes AIDA-1, a postsynaptic scaffold protein whose PTB domain binds NPxF-motifs of SynGAP family proteins and whose C-terminus anchors it to PSD-95; CaMKII-mediated phosphorylation displaces AIDA-1 from the PSD core upon synaptic activity, releasing it to translocate to the nucleus (facilitated by SAM-domain uncoupling that exposes a buried NLS) where it regulates nucleolar assembly and protein synthesis; at synapses, AIDA-1 facilitates ER-to-synapse trafficking of GluN2B-containing NMDARs via association with CASK and KIF17, thereby controlling NMDAR subunit composition and plasticity; in oligodendrocytes, AIDA-1 regulates Rac1 activity to control myelination; and in ischemia, lactylation at K1222 targets ANKS1B for proteasomal degradation as a neuroprotective brake on GluN2B surface expression.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ANKS1B encodes AIDA-1, a multidomain postsynaptic scaffold protein that orchestrates NMDA receptor trafficking, synaptic signaling, and nuclear functions in neurons and oligodendrocytes. At synapses, AIDA-1 anchors to PSD-95 via its C-terminus and binds SynGAP family proteins through its PTB domain; it facilitates ER-to-synapse transport of GluN2B-containing NMDARs through association with CASK and KIF17, and CaMKII-mediated phosphorylation displaces AIDA-1 from the PSD core upon synaptic activity, enabling its translocation to the nucleus where SAM-domain uncoupling exposes a buried NLS and AIDA-1 promotes nucleolar assembly and protein synthesis [PMID:26085624, PMID:27477489, PMID:17334360, PMID:19666031, PMID:38759928]. In oligodendrocytes, AIDA-1 regulates Rac1 activity to control myelination and maturation, and cell-type-specific loss from the oligodendrocyte lineage causes social and sensory deficits rescuable by clemastine [PMID:38129387]. Haploinsufficiency of ANKS1B in mice produces neurodevelopmental phenotypes including social deficits and hyperactivity, and under ischemic conditions, lactylation at K1222 targets AIDA-1 for proteasomal degradation as a neuroprotective brake on GluN2B surface expression and excitotoxic calcium overload [PMID:31388001, PMID:41564684].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Identification of AIDA-1 as an intracellular binding partner of amyloid precursor protein established the gene product as a multi-isoform PTB-domain protein with isoform-specific subcellular distributions.\",\n      \"evidence\": \"Co-immunoprecipitation and in vitro binding in leukemia cell lines and transfected cells\",\n      \"pmids\": [\"15004329\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological significance of APP interaction in neurons not demonstrated\", \"No in vivo validation\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Discovery that the AIDA-1c isoform binds the Cajal body marker coilin and competes with SmB' for coilin binding revealed a nuclear role for ANKS1B in snRNP body organization, with knockdown altering Cajal body integrity and reducing cell viability.\",\n      \"evidence\": \"Co-immunoprecipitation, competition binding, siRNA knockdown with fluorescence microscopy\",\n      \"pmids\": [\"15862129\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which AIDA-1c reaches the nucleus was unknown\", \"Cajal body phenotype not confirmed in neurons\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstration that AIDA-1d resides in the PSD via PSD-95 binding and translocates to the nucleus upon NMDA stimulation — where it drives Cajal body–nucleolar association and increases protein synthesis — established the first activity-dependent synapse-to-nucleus signaling function for this protein.\",\n      \"evidence\": \"Co-IP, live-cell imaging, NMDA stimulation, siRNA knockdown with protein synthesis assay in cultured neurons\",\n      \"pmids\": [\"17334360\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ca²⁺-independent translocation mechanism was not resolved\", \"In vivo relevance of nucleolar regulation not tested\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"NMR structure of the tandem SAM domains revealed that the NLS is buried at the SAM–SAM interface and that differential thermal stability of the two domains provides a structural mechanism for NLS exposure, explaining how AIDA-1 can switch between synaptic retention and nuclear import.\",\n      \"evidence\": \"NMR structure determination and thermal stability analysis\",\n      \"pmids\": [\"19666031\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No direct demonstration that SAM uncoupling occurs in living neurons upon stimulation\", \"Upstream signal triggering SAM uncoupling not identified\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Conditional forebrain knockout and biochemical studies showed AIDA-1 associates with CASK and KIF17 to facilitate ER-to-synapse transport of GluN2B-containing NMDARs; loss of AIDA-1 shifted synaptic NMDAR composition from GluN2B- to GluN2A-mediated transmission, defining AIDA-1 as a key determinant of NMDAR subunit composition.\",\n      \"evidence\": \"Conditional knockout, co-IP, subcellular fractionation, electrophysiology, shRNA knockdown in cultured neurons\",\n      \"pmids\": [\"26085624\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct interaction surface between AIDA-1 and CASK/KIF17 not mapped\", \"Whether AIDA-1 rides with the transport vesicle or acts at the ER exit site was unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Immuno-electron microscopy placed AIDA-1 within the PSD dense core (~30 nm from the membrane) under basal conditions and showed reversible activity-dependent redistribution to ~55 nm, providing ultrastructural evidence for stimulus-driven PSD reorganization of this scaffold.\",\n      \"evidence\": \"Immunogold EM with two distinct antibodies in cultured hippocampal neurons\",\n      \"pmids\": [\"26356309\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The kinase responsible for the displacement was not yet identified\", \"Nuclear translocation was not tracked at the EM level\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identification of CaMKII as the kinase that phosphorylates AIDA-1 in PSD fractions, with pharmacological inhibition blocking activity-induced displacement, resolved the signaling mechanism coupling synaptic activity to AIDA-1 release from the PSD core.\",\n      \"evidence\": \"Biochemical phosphorylation assay of brain PSD fractions, immuno-EM with CaMKII inhibitor tatCN21\",\n      \"pmids\": [\"27477489\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific phosphorylation site(s) on AIDA-1 not identified\", \"Whether phosphorylation is necessary for nuclear translocation versus merely PSD release was not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Haploinsufficiency in mice reproduced social deficits, hyperactivity, and sensorimotor dysfunction, and quantitative interactome profiling placed AIDA-1 at the hub of synaptic protein networks, establishing ANKS1B as a neurodevelopmental disease gene.\",\n      \"evidence\": \"Quantitative MS-based interactome in neurons, heterozygous knockout mouse with behavioral phenotyping\",\n      \"pmids\": [\"31388001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific interactors driving each behavioral phenotype not dissected\", \"Human genetic validation for neurodevelopmental disorder not shown in this study\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Cell-type-specific knockout from the oligodendrocyte lineage — but not neurons — recapitulated social and sensory deficits, and these were rescued by clemastine, revealing a previously unsuspected oligodendroglial function of AIDA-1 mediated by Rac1 activity control of myelination.\",\n      \"evidence\": \"Conditional oligodendrocyte-lineage knockout, MRI white matter imaging, Rac1 activity assay, pharmacological rescue with clemastine\",\n      \"pmids\": [\"38129387\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular link between AIDA-1 and Rac1 activation not defined\", \"Whether neuronal and oligodendroglial AIDA-1 functions are independent or synergistic in vivo is unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Crystal structure of the AIDA-1 PTB domain bound to the SynGAP NPxF motif provided the atomic-resolution basis for how AIDA-1 recognizes and anchors SynGAP family Ras-GAPs at the PSD.\",\n      \"evidence\": \"X-ray crystallography, affinity purification, and biochemical binding assays\",\n      \"pmids\": [\"38759928\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of disrupting the AIDA-1–SynGAP interaction on synaptic Ras signaling not tested in neurons\", \"Whether other PTB-binding partners compete with SynGAP at the PSD is unknown\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Discovery that ischemia-induced lactylation at K1222 triggers ubiquitin-proteasome-mediated AIDA-1 degradation, causing GluN2B ER retention, established a metabolic post-translational mechanism that limits excitotoxicity by reducing surface NMDAR expression.\",\n      \"evidence\": \"OGD/R cell model, proteomics, K1222R mutagenesis, Ca²⁺ imaging, surface trafficking assay\",\n      \"pmids\": [\"41564684\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Lactylation-driven degradation not validated in vivo in ischemia models\", \"The E3 ubiquitin ligase mediating AIDA-1 ubiquitination is unidentified\", \"Single lab finding\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the specific CaMKII phosphorylation site(s) on AIDA-1, whether SAM-domain uncoupling is triggered by phosphorylation or an independent signal, the molecular basis of AIDA-1's regulation of Rac1 in oligodendrocytes, and how the PTB-mediated SynGAP interaction coordinates with GluN2B trafficking functions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"CaMKII phosphorylation site(s) unmapped\", \"SAM uncoupling trigger unresolved\", \"AIDA-1–Rac1 mechanism in oligodendrocytes undefined\", \"No integrative structural model of full-length AIDA-1 in the PSD\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 4, 10]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 5, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 5, 7]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [4, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [2, 4, 5, 7, 8, 10]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7, 9, 11]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [4, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [8, 9]}\n    ],\n    \"complexes\": [\n      \"PSD-95/AIDA-1 postsynaptic complex\"\n    ],\n    \"partners\": [\n      \"DLG4\",\n      \"SYNGAP1\",\n      \"CASK\",\n      \"KIF17\",\n      \"GRIN2B\",\n      \"COIL\",\n      \"KRIT1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}