{"gene":"KIF21B","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":1999,"finding":"KIF21B is a plus end-directed kinesin motor protein highly enriched in dendrites (not axons) of neurons, and contains a WD-40 repeat domain potentially involved in cargo binding. Its dendritic enrichment despite plus-end directionality indicated a novel kinesin sorting mechanism beyond minus-end-directed motor activity.","method":"Immunolocalization in neurons, motor domain analysis, identification of WD-40 domain","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional interpretation, single lab, multiple cell biological methods","pmids":["10225949"],"is_preprint":false},{"year":2013,"finding":"The ubiquitin E3 ligase TRIM3 interacts with KIF21B via its RBCC domain, co-localizes with KIF21B at intracellular and Golgi-derived vesicles in neurons, and positively regulates KIF21B motor motility (TRIM3 depletion reduces KIF21B motility) without targeting KIF21B for degradation.","method":"Co-immunoprecipitation, co-localization in neurons, Trim3 knockout mice, TRIM3 overexpression in cultured neurons, motility assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction demonstrated, loss-of-function with defined motility phenotype, single lab","pmids":["24086586"],"is_preprint":false},{"year":2014,"finding":"KIF21B interacts with (co-precipitates and co-localizes with) the GABAA receptor γ2 subunit in hippocampal neurons, and KIF21B knockdown reduces γ2-subunit-containing GABAAR clusters in neurites and at the cell surface, indicating KIF21B mediates dendritic delivery of GABAAR transport vesicles.","method":"Co-immunoprecipitation, co-localization, shRNA knockdown, surface receptor quantification in cultured neurons","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional knockdown phenotype, single lab, two orthogonal methods","pmids":["25172774"],"is_preprint":false},{"year":2016,"finding":"KIF21B is a processive motor protein that also regulates microtubule dynamics: in Kif21b knockout neurons, microtubules grow more slowly and persistently, leading to tighter packing in dendrites, decreased dendritic arbor complexity, reduced spine density, and deficits in synaptic transmission. Kif21b-null mice show learning and memory deficits.","method":"Kif21b knockout mice, live cell microtubule dynamics imaging, dendritic morphology quantification, electrophysiology, behavioral assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — complete knockout model with multiple orthogonal cellular and in vivo readouts, replicated across assays","pmids":["27117409"],"is_preprint":false},{"year":2017,"finding":"KIF21B is a processive kinesin-4 motor that accumulates at microtubule plus ends and induces pausing. Even a few KIF21B molecules are sufficient to strongly inhibit microtubule plus-end growth in vitro. The pause-inducing activity depends on non-motor microtubule-binding domains in the stalk region and the C-terminal WD40 domain. The WD40 tail preferentially binds GTP-type over GDP-type microtubule lattice, contributing to plus-end association. KIF21B also contains a motor-inhibiting (autoinhibitory) domain that, rather than blocking microtubule interaction, enhances pause induction by preventing KIF21B detachment from microtubule tips.","method":"In vitro reconstitution with purified KIF21B, TIRF microscopy, domain deletion/mutation analysis, microtubule lattice-binding assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified protein, mutagenesis of multiple domains, multiple orthogonal methods in single rigorous study","pmids":["28290984"],"is_preprint":false},{"year":2018,"finding":"KIF21B interacts with the Rac1GEF subunit ELMO1 in an NMDAR-LTD stimulus-dependent manner, leading to ELMO1 translocation out of dendritic spines into endosomes. This KIF21B-mediated sequestration terminates Rac1 activation, causes spine shrinkage, facilitates AMPAR endocytosis, and reduces postsynaptic strength, constituting a mechanism for NMDAR-dependent LTD underlying fear extinction.","method":"Kif21b knockout mice, co-immunoprecipitation, live imaging of ELMO1 in spines, fear extinction behavioral assays, pharmacological rescue with CPYPP","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — knockout model, Co-IP, live imaging, pharmacological rescue, multiple orthogonal methods establishing pathway","pmids":["29949770"],"is_preprint":false},{"year":2018,"finding":"KIF21B constrains the dynamics of neurobeachin (NBEA) and is present in the NBEA–recycling endosome–GluN2B-NMDAR complex. Kif21b knockout decreases GluN2B-NMDAR surface expression and alters social behavior in mice, indicating KIF21B regulates endocytic recycling and local re-insertion of GluN2B-NMDARs at synapses.","method":"Kif21b knockout mice, co-immunoprecipitation, live imaging of NBEA in spines, surface receptor quantification, social behavior assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — knockout model with Co-IP, live imaging, surface receptor assays, and behavioral readout; multiple orthogonal methods","pmids":["29847800"],"is_preprint":false},{"year":2018,"finding":"KIF21B knockdown in hippocampal neurons increases excitatory post-synaptic current frequency and amplitude, indicating KIF21B functions as an inhibitory constraint on excitatory synaptic transmission through a mechanism distinct from pre-synaptic NMDAR activity (unlike Kif11).","method":"RNAi knockdown, whole-cell patch-clamp electrophysiology in primary hippocampal neurons","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean knockdown with defined electrophysiological readout, single lab, single method","pmids":["30479371"],"is_preprint":false},{"year":2020,"finding":"KIF21B restricts microtubule length in T cells by inducing microtubule pausing followed by catastrophe. KIF21B knockout causes microtubule overgrowth that perturbs dynein-driven centrosome translocation to the immunological synapse. Catastrophe induction with vinblastine rescues centrosome polarization in KIF21B-knockout T cells.","method":"KIF21B knockout T cells, live microtubule imaging, vinblastine pharmacological rescue, biophysical simulations of dynein-mediated pulling forces","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — knockout model, live imaging, pharmacological rescue, computational modeling; multiple orthogonal approaches","pmids":["33346730"],"is_preprint":false},{"year":2020,"finding":"Missense variants in KIF21B associated with neurodevelopmental disorders impede neuronal migration by attenuating kinesin autoinhibition, leading to aberrant (excess) KIF21B motility activity. An ACC-associated variant independently disrupts axonal growth and ipsilateral axon branching via deregulation of canonical kinesin motor activity. Kif21b haploinsufficiency impairs neuronal positioning in vivo.","method":"In vivo expression of KIF21B variants via in utero electroporation in mouse, neuronal migration assays, axonal growth quantification, motor activity measurements","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo mouse model with patient-derived variants, multiple cellular and neuroanatomical readouts, mechanistic dissection of autoinhibition","pmids":["32415109"],"is_preprint":false},{"year":2023,"finding":"Kif21b directly binds and regulates the actin cytoskeleton (both in vitro and in vivo), influencing branching and nucleokinesis during radial glia-guided locomotion of cortical projection neurons, independently of its microtubule motor activity. This constitutes a non-canonical function of Kif21b on actin cytoskeleton during neuronal migration.","method":"In utero electroporation in mouse, live imaging on cultured cortical slices, in vitro actin binding assays, in vivo actin dynamics analysis in migratory neurons","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro actin binding reconstitution plus in vivo loss-of-function imaging, two orthogonal methods, single lab","pmids":["37418324"],"is_preprint":false},{"year":2023,"finding":"Kif21b binds GKAP (guanylate kinase-associated protein) and myosin Va, localizes in dendritic spines in a myosin Va- and neuronal activity-dependent manner, and regulates actin dynamics in spines. Kif21b depletion impairs actin turnover adaptation following chronic activity. Kif21b overexpression promotes actin polymerization. Kif21b controls GKAP removal from spines and reduction of surface GluA2-AMPARs, mediating homeostatic synaptic downscaling.","method":"Co-immunoprecipitation, live actin imaging in spines, Kif21b knockout neurons, overexpression assays, surface receptor quantification, chronic activity protocols","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, knockout model, overexpression, live imaging, surface receptor assays; multiple orthogonal methods, single lab","pmids":["37418322"],"is_preprint":false},{"year":2023,"finding":"KIF21B is required for estradiol- and BDNF-mediated neuronal morphology changes in hippocampal neurons. Kif21b silencing abolishes estradiol and BDNF effects on both axon and dendrite morphology, and also decreases Ngn3 expression. This places KIF21B in an Estradiol/BDNF/TrkB/KIF21B/Ngn3 signaling pathway regulating neuritogenesis.","method":"siRNA knockdown of Kif21b in cultured hippocampal neurons, morphological analysis, pharmacological TrkB inhibition, Ngn3 expression assays","journal":"Frontiers in molecular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined morphological readout, epistasis placement in pathway, single lab","pmids":["37078090"],"is_preprint":false}],"current_model":"KIF21B is a processive plus end-directed kinesin-4 motor enriched in neuronal dendrites that performs dual functions: it transports cargoes (including GABAA receptor γ2 subunits, GluN2B-NMDARs via the NBEA-recycling endosome complex, and ELMO1) along microtubules, and autonomously regulates microtubule dynamics by inducing pausing and catastrophe through its stalk-region non-motor microtubule-binding domains and C-terminal WD40 domain (which prefers GTP-type lattice), with its autoinhibitory domain enhancing pause induction rather than blocking microtubule interaction; additionally, KIF21B directly binds and regulates actin cytoskeleton dynamics in a non-canonical manner to control neuronal migration, spine actin turnover, and homeostatic synaptic downscaling; its motility is positively regulated by TRIM3 (via RBCC-domain interaction) and its autoinhibition is disrupted by neurodevelopmental-disorder-associated missense variants, causing aberrant motor activity and impaired neuronal migration."},"narrative":{"mechanistic_narrative":"KIF21B is a processive plus end-directed kinesin-4 motor enriched in neuronal dendrites that couples microtubule-based cargo transport with autonomous control of cytoskeletal dynamics to shape neuronal architecture and synaptic function [PMID:10225949, PMID:27117409, PMID:28290984]. Beyond translocating along microtubules, KIF21B accumulates at growing plus ends and induces pausing and catastrophe through non-motor microtubule-binding domains in its stalk and a C-terminal WD40 domain that preferentially engages the GTP-type lattice; its autoinhibitory domain enhances pause induction by preventing detachment from microtubule tips rather than blocking lattice binding [PMID:28290984]. This length-restricting activity has consequences across cell types: in neurons it controls microtubule growth, dendritic arborization, spine density and synaptic transmission [PMID:27117409], and in T cells it limits microtubule overgrowth to permit dynein-driven centrosome translocation to the immunological synapse [PMID:33346730]. As a transporter and scaffold, KIF21B delivers and regulates synaptic receptors and signaling complexes, mediating dendritic delivery of GABAA receptor γ2-subunit vesicles [PMID:25172774], regulating endocytic recycling of GluN2B-NMDARs within an NBEA–recycling endosome complex [PMID:29847800], and sequestering the Rac1-GEF ELMO1 out of spines in an NMDAR-LTD-dependent manner to terminate Rac1 signaling and drive long-term depression [PMID:29949770]. KIF21B additionally binds and regulates the actin cytoskeleton independently of its motor activity, controlling branching and nucleokinesis during neuronal migration [PMID:37418324] and, via interactions with GKAP and myosin Va, driving spine actin turnover and GKAP/GluA2-AMPAR removal during homeostatic synaptic downscaling [PMID:37418322]. Its motility is positively regulated by the E3 ligase TRIM3 through an RBCC-domain interaction without degradation [PMID:24086586], and neurodevelopmental-disorder-associated missense variants impair neuronal migration by attenuating autoinhibition and producing aberrant excess motor activity [PMID:32415109].","teleology":[{"year":1999,"claim":"Established that a plus end-directed kinesin could be selectively enriched in dendrites, raising the question of how directional motors achieve compartment-specific localization.","evidence":"Immunolocalization in neurons and motor/WD-40 domain analysis","pmids":["10225949"],"confidence":"Medium","gaps":["Cargo bound by the WD-40 domain not identified","Mechanism of dendritic sorting unresolved"]},{"year":2013,"claim":"Identified a non-degradative regulator of KIF21B motility, showing motor activity is positively tuned by a binding partner rather than solely intrinsic.","evidence":"Co-IP, co-localization at Golgi-derived vesicles, Trim3 knockout mice and motility assays","pmids":["24086586"],"confidence":"Medium","gaps":["Molecular mechanism by which TRIM3 enhances motility unknown","Single lab"]},{"year":2014,"claim":"Assigned a defined transport cargo to KIF21B, demonstrating it delivers inhibitory receptor vesicles to dendrites and the surface.","evidence":"Co-IP, co-localization, shRNA knockdown and surface receptor quantification in neurons","pmids":["25172774"],"confidence":"Medium","gaps":["Direct vs adaptor-mediated binding to GABAAR γ2 not resolved","Single lab, two methods"]},{"year":2016,"claim":"Revealed that KIF21B is not only a transporter but a regulator of microtubule dynamics whose loss alters dendrite and spine architecture and impairs learning in vivo.","evidence":"Kif21b knockout mice, live microtubule imaging, morphology, electrophysiology, behavior","pmids":["27117409"],"confidence":"High","gaps":["Whether dynamics effects are direct or via cargo not separated in vivo","Molecular basis of microtubule regulation not defined here"]},{"year":2017,"claim":"Defined the biophysical mechanism of KIF21B's microtubule regulation, localizing pause-induction to stalk non-motor and WD40 domains and redefining the autoinhibitory domain's role.","evidence":"In vitro reconstitution with purified KIF21B, TIRF microscopy, domain mutagenesis, lattice-binding assays","pmids":["28290984"],"confidence":"High","gaps":["How autoinhibition is relieved physiologically not established","Structural basis of GTP-lattice preference unresolved"]},{"year":2018,"claim":"Connected KIF21B to activity-dependent synaptic depression by showing it sequesters the Rac1-GEF ELMO1 to terminate Rac1 signaling and drive LTD.","evidence":"Kif21b knockout mice, Co-IP, live ELMO1 imaging, fear extinction behavior, CPYPP rescue","pmids":["29949770"],"confidence":"High","gaps":["Stimulus-dependence of KIF21B-ELMO1 binding mechanism unclear","Link between transport and signaling termination not fully separated"]},{"year":2018,"claim":"Placed KIF21B in an NBEA–recycling endosome complex controlling GluN2B-NMDAR surface recycling, linking it to social behavior.","evidence":"Kif21b knockout mice, Co-IP, live NBEA imaging, surface receptor and social behavior assays","pmids":["29847800"],"confidence":"High","gaps":["Direct binding partner within complex not pinpointed","Mechanism of recycling control vs transport not separated"]},{"year":2018,"claim":"Showed KIF21B acts as an inhibitory constraint on excitatory transmission, distinct from other kinesins.","evidence":"RNAi knockdown and whole-cell patch-clamp in hippocampal neurons","pmids":["30479371"],"confidence":"Medium","gaps":["Molecular basis of the constraint not defined","Single method, single lab"]},{"year":2020,"claim":"Generalized the length-restricting function beyond neurons, showing KIF21B-induced catastrophe enables centrosome polarization to the immunological synapse in T cells.","evidence":"KIF21B knockout T cells, live imaging, vinblastine rescue, biophysical simulations","pmids":["33346730"],"confidence":"High","gaps":["Whether the same domains operate in T cells not tested directly","Cargo functions in T cells not addressed"]},{"year":2020,"claim":"Linked disease variants to a defined mechanism, showing attenuated autoinhibition produces excess motility that impairs neuronal migration.","evidence":"In utero electroporation of patient variants in mouse, migration and axon assays, motor activity measurement","pmids":["32415109"],"confidence":"High","gaps":["Named Mendelian disorder not formally defined in timeline","Genotype-phenotype range across variants not fully mapped"]},{"year":2023,"claim":"Established a motor-independent function for KIF21B in directly binding and regulating actin during neuronal migration.","evidence":"In utero electroporation, slice live imaging, in vitro actin binding, in vivo actin dynamics","pmids":["37418324"],"confidence":"High","gaps":["Actin-binding domain not mapped","Coordination between actin and microtubule activities unclear"]},{"year":2023,"claim":"Defined a KIF21B–GKAP–myosin Va axis controlling spine actin turnover and AMPAR removal during homeostatic downscaling.","evidence":"Co-IP, live actin imaging, Kif21b knockout neurons, overexpression, surface receptor assays, chronic activity protocols","pmids":["37418322"],"confidence":"High","gaps":["Direct vs indirect binding to GKAP/myosin Va not fully resolved","How activity gates spine localization not mechanistically defined"]},{"year":2023,"claim":"Positioned KIF21B downstream of estradiol/BDNF/TrkB signaling in neuritogenesis.","evidence":"siRNA knockdown, morphological analysis, TrkB inhibition, Ngn3 expression assays","pmids":["37078090"],"confidence":"Medium","gaps":["Mechanism connecting KIF21B to Ngn3 expression unknown","Single lab, correlative pathway placement"]},{"year":null,"claim":"How KIF21B's microtubule-regulating, actin-binding, and cargo-transport activities are physiologically coordinated and switched within a single cell remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated structural model of full-length regulation","Triggers that relieve autoinhibition in vivo unknown","Relationship between actin and microtubule functions undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,3,4]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[4]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4,10,11]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[4,8,10]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1,6]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[3,5,6,7,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[9,10]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2,6]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[8]}],"complexes":["NBEA–recycling endosome–GluN2B-NMDAR complex"],"partners":["TRIM3","ELMO1","NBEA","GKAP","MYO5A","GABRG2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O75037","full_name":"Kinesin-like protein KIF21B","aliases":[],"length_aa":1637,"mass_kda":182.7,"function":"Plus-end directed microtubule-dependent motor protein which displays processive activity. Is involved in regulation of microtubule dynamics, synapse function and neuronal morphology, including dendritic tree branching and spine formation. Plays a role in lerning and memory. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptor to cell surface","subcellular_location":"Cytoplasm, cytoskeleton; Cell projection, dendrite; Cell projection, growth cone; Cell projection, axon; Cytoplasmic vesicle","url":"https://www.uniprot.org/uniprotkb/O75037/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF21B","classification":"Not Classified","n_dependent_lines":14,"n_total_lines":1208,"dependency_fraction":0.011589403973509934},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"PFDN6","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KIF21B","total_profiled":1310},"omim":[{"mim_id":"608322","title":"KINESIN FAMILY MEMBER 21B; KIF21B","url":"https://www.omim.org/entry/608322"},{"mim_id":"608283","title":"KINESIN FAMILY MEMBER 21A; KIF21A","url":"https://www.omim.org/entry/608283"},{"mim_id":"126200","title":"MULTIPLE SCLEROSIS, SUSCEPTIBILITY TO; MS","url":"https://www.omim.org/entry/126200"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Plasma membrane","reliability":"Uncertain"},{"location":"Mid piece","reliability":"Uncertain"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":32.3},{"tissue":"brain","ntpm":19.3},{"tissue":"retina","ntpm":19.9}],"url":"https://www.proteinatlas.org/search/KIF21B"},"hgnc":{"alias_symbol":["DKFZP434J212","KIAA0449"],"prev_symbol":[]},"alphafold":{"accession":"O75037","domains":[{"cath_id":"3.40.850.10","chopping":"11-102_116-125_138-164_173-241_261-383","consensus_level":"medium","plddt":88.1861,"start":11,"end":383},{"cath_id":"1.10.287,1.10.287","chopping":"635-694_703-807","consensus_level":"medium","plddt":81.6638,"start":635,"end":807},{"cath_id":"-","chopping":"941-1065","consensus_level":"medium","plddt":81.0018,"start":941,"end":1065},{"cath_id":"2.130.10.10","chopping":"1284-1403_1411-1632","consensus_level":"medium","plddt":86.7797,"start":1284,"end":1632}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75037","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75037-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75037-F1-predicted_aligned_error_v6.png","plddt_mean":69.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF21B","jax_strain_url":"https://www.jax.org/strain/search?query=KIF21B"},"sequence":{"accession":"O75037","fasta_url":"https://rest.uniprot.org/uniprotkb/O75037.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75037/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75037"}},"corpus_meta":[{"pmid":"10225949","id":"PMC_10225949","title":"Novel dendritic kinesin sorting identified by different process targeting of two related kinesins: KIF21A and KIF21B.","date":"1999","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10225949","citation_count":142,"is_preprint":false},{"pmid":"27117409","id":"PMC_27117409","title":"The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory.","date":"2016","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/27117409","citation_count":74,"is_preprint":false},{"pmid":"28290984","id":"PMC_28290984","title":"Kinesin-4 KIF21B is a potent microtubule pausing factor.","date":"2017","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/28290984","citation_count":47,"is_preprint":false},{"pmid":"29847800","id":"PMC_29847800","title":"Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior.","date":"2018","source":"Cell 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neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/37078090","citation_count":4,"is_preprint":false},{"pmid":"39239553","id":"PMC_39239553","title":"Mitochondrial ATP Synthesis and Proton Transport Synergistically Mitigate Oligodendrocyte Progenitor Cell Dysfunction Following Transient Middle Cerebral Artery Occlusion via the Pbx3/Dguok/Kif21b Signaling Pathway.","date":"2024","source":"International journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39239553","citation_count":1,"is_preprint":false},{"pmid":"42122124","id":"PMC_42122124","title":"KIF21B, Ubiquitinated by TRIM3, Exerts Oncogenic Role in T-Cell Acute Lymphoblastic Leukemia by Activating Wnt/β-Catenin Pathway.","date":"2026","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/42122124","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11572,"output_tokens":3455,"usd":0.043271,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11049,"output_tokens":3991,"usd":0.07751,"stage2_stop_reason":"end_turn"},"total_usd":0.120781,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"KIF21B is a plus end-directed kinesin motor protein highly enriched in dendrites (not axons) of neurons, and contains a WD-40 repeat domain potentially involved in cargo binding. Its dendritic enrichment despite plus-end directionality indicated a novel kinesin sorting mechanism beyond minus-end-directed motor activity.\",\n      \"method\": \"Immunolocalization in neurons, motor domain analysis, identification of WD-40 domain\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional interpretation, single lab, multiple cell biological methods\",\n      \"pmids\": [\"10225949\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The ubiquitin E3 ligase TRIM3 interacts with KIF21B via its RBCC domain, co-localizes with KIF21B at intracellular and Golgi-derived vesicles in neurons, and positively regulates KIF21B motor motility (TRIM3 depletion reduces KIF21B motility) without targeting KIF21B for degradation.\",\n      \"method\": \"Co-immunoprecipitation, co-localization in neurons, Trim3 knockout mice, TRIM3 overexpression in cultured neurons, motility assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction demonstrated, loss-of-function with defined motility phenotype, single lab\",\n      \"pmids\": [\"24086586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KIF21B interacts with (co-precipitates and co-localizes with) the GABAA receptor γ2 subunit in hippocampal neurons, and KIF21B knockdown reduces γ2-subunit-containing GABAAR clusters in neurites and at the cell surface, indicating KIF21B mediates dendritic delivery of GABAAR transport vesicles.\",\n      \"method\": \"Co-immunoprecipitation, co-localization, shRNA knockdown, surface receptor quantification in cultured neurons\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional knockdown phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"25172774\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KIF21B is a processive motor protein that also regulates microtubule dynamics: in Kif21b knockout neurons, microtubules grow more slowly and persistently, leading to tighter packing in dendrites, decreased dendritic arbor complexity, reduced spine density, and deficits in synaptic transmission. Kif21b-null mice show learning and memory deficits.\",\n      \"method\": \"Kif21b knockout mice, live cell microtubule dynamics imaging, dendritic morphology quantification, electrophysiology, behavioral assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — complete knockout model with multiple orthogonal cellular and in vivo readouts, replicated across assays\",\n      \"pmids\": [\"27117409\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KIF21B is a processive kinesin-4 motor that accumulates at microtubule plus ends and induces pausing. Even a few KIF21B molecules are sufficient to strongly inhibit microtubule plus-end growth in vitro. The pause-inducing activity depends on non-motor microtubule-binding domains in the stalk region and the C-terminal WD40 domain. The WD40 tail preferentially binds GTP-type over GDP-type microtubule lattice, contributing to plus-end association. KIF21B also contains a motor-inhibiting (autoinhibitory) domain that, rather than blocking microtubule interaction, enhances pause induction by preventing KIF21B detachment from microtubule tips.\",\n      \"method\": \"In vitro reconstitution with purified KIF21B, TIRF microscopy, domain deletion/mutation analysis, microtubule lattice-binding assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified protein, mutagenesis of multiple domains, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"28290984\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KIF21B interacts with the Rac1GEF subunit ELMO1 in an NMDAR-LTD stimulus-dependent manner, leading to ELMO1 translocation out of dendritic spines into endosomes. This KIF21B-mediated sequestration terminates Rac1 activation, causes spine shrinkage, facilitates AMPAR endocytosis, and reduces postsynaptic strength, constituting a mechanism for NMDAR-dependent LTD underlying fear extinction.\",\n      \"method\": \"Kif21b knockout mice, co-immunoprecipitation, live imaging of ELMO1 in spines, fear extinction behavioral assays, pharmacological rescue with CPYPP\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — knockout model, Co-IP, live imaging, pharmacological rescue, multiple orthogonal methods establishing pathway\",\n      \"pmids\": [\"29949770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KIF21B constrains the dynamics of neurobeachin (NBEA) and is present in the NBEA–recycling endosome–GluN2B-NMDAR complex. Kif21b knockout decreases GluN2B-NMDAR surface expression and alters social behavior in mice, indicating KIF21B regulates endocytic recycling and local re-insertion of GluN2B-NMDARs at synapses.\",\n      \"method\": \"Kif21b knockout mice, co-immunoprecipitation, live imaging of NBEA in spines, surface receptor quantification, social behavior assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — knockout model with Co-IP, live imaging, surface receptor assays, and behavioral readout; multiple orthogonal methods\",\n      \"pmids\": [\"29847800\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KIF21B knockdown in hippocampal neurons increases excitatory post-synaptic current frequency and amplitude, indicating KIF21B functions as an inhibitory constraint on excitatory synaptic transmission through a mechanism distinct from pre-synaptic NMDAR activity (unlike Kif11).\",\n      \"method\": \"RNAi knockdown, whole-cell patch-clamp electrophysiology in primary hippocampal neurons\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean knockdown with defined electrophysiological readout, single lab, single method\",\n      \"pmids\": [\"30479371\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF21B restricts microtubule length in T cells by inducing microtubule pausing followed by catastrophe. KIF21B knockout causes microtubule overgrowth that perturbs dynein-driven centrosome translocation to the immunological synapse. Catastrophe induction with vinblastine rescues centrosome polarization in KIF21B-knockout T cells.\",\n      \"method\": \"KIF21B knockout T cells, live microtubule imaging, vinblastine pharmacological rescue, biophysical simulations of dynein-mediated pulling forces\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — knockout model, live imaging, pharmacological rescue, computational modeling; multiple orthogonal approaches\",\n      \"pmids\": [\"33346730\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Missense variants in KIF21B associated with neurodevelopmental disorders impede neuronal migration by attenuating kinesin autoinhibition, leading to aberrant (excess) KIF21B motility activity. An ACC-associated variant independently disrupts axonal growth and ipsilateral axon branching via deregulation of canonical kinesin motor activity. Kif21b haploinsufficiency impairs neuronal positioning in vivo.\",\n      \"method\": \"In vivo expression of KIF21B variants via in utero electroporation in mouse, neuronal migration assays, axonal growth quantification, motor activity measurements\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo mouse model with patient-derived variants, multiple cellular and neuroanatomical readouts, mechanistic dissection of autoinhibition\",\n      \"pmids\": [\"32415109\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Kif21b directly binds and regulates the actin cytoskeleton (both in vitro and in vivo), influencing branching and nucleokinesis during radial glia-guided locomotion of cortical projection neurons, independently of its microtubule motor activity. This constitutes a non-canonical function of Kif21b on actin cytoskeleton during neuronal migration.\",\n      \"method\": \"In utero electroporation in mouse, live imaging on cultured cortical slices, in vitro actin binding assays, in vivo actin dynamics analysis in migratory neurons\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro actin binding reconstitution plus in vivo loss-of-function imaging, two orthogonal methods, single lab\",\n      \"pmids\": [\"37418324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Kif21b binds GKAP (guanylate kinase-associated protein) and myosin Va, localizes in dendritic spines in a myosin Va- and neuronal activity-dependent manner, and regulates actin dynamics in spines. Kif21b depletion impairs actin turnover adaptation following chronic activity. Kif21b overexpression promotes actin polymerization. Kif21b controls GKAP removal from spines and reduction of surface GluA2-AMPARs, mediating homeostatic synaptic downscaling.\",\n      \"method\": \"Co-immunoprecipitation, live actin imaging in spines, Kif21b knockout neurons, overexpression assays, surface receptor quantification, chronic activity protocols\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, knockout model, overexpression, live imaging, surface receptor assays; multiple orthogonal methods, single lab\",\n      \"pmids\": [\"37418322\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KIF21B is required for estradiol- and BDNF-mediated neuronal morphology changes in hippocampal neurons. Kif21b silencing abolishes estradiol and BDNF effects on both axon and dendrite morphology, and also decreases Ngn3 expression. This places KIF21B in an Estradiol/BDNF/TrkB/KIF21B/Ngn3 signaling pathway regulating neuritogenesis.\",\n      \"method\": \"siRNA knockdown of Kif21b in cultured hippocampal neurons, morphological analysis, pharmacological TrkB inhibition, Ngn3 expression assays\",\n      \"journal\": \"Frontiers in molecular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined morphological readout, epistasis placement in pathway, single lab\",\n      \"pmids\": [\"37078090\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIF21B is a processive plus end-directed kinesin-4 motor enriched in neuronal dendrites that performs dual functions: it transports cargoes (including GABAA receptor γ2 subunits, GluN2B-NMDARs via the NBEA-recycling endosome complex, and ELMO1) along microtubules, and autonomously regulates microtubule dynamics by inducing pausing and catastrophe through its stalk-region non-motor microtubule-binding domains and C-terminal WD40 domain (which prefers GTP-type lattice), with its autoinhibitory domain enhancing pause induction rather than blocking microtubule interaction; additionally, KIF21B directly binds and regulates actin cytoskeleton dynamics in a non-canonical manner to control neuronal migration, spine actin turnover, and homeostatic synaptic downscaling; its motility is positively regulated by TRIM3 (via RBCC-domain interaction) and its autoinhibition is disrupted by neurodevelopmental-disorder-associated missense variants, causing aberrant motor activity and impaired neuronal migration.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF21B is a processive plus end-directed kinesin-4 motor enriched in neuronal dendrites that couples microtubule-based cargo transport with autonomous control of cytoskeletal dynamics to shape neuronal architecture and synaptic function [#0, #3, #4]. Beyond translocating along microtubules, KIF21B accumulates at growing plus ends and induces pausing and catastrophe through non-motor microtubule-binding domains in its stalk and a C-terminal WD40 domain that preferentially engages the GTP-type lattice; its autoinhibitory domain enhances pause induction by preventing detachment from microtubule tips rather than blocking lattice binding [#4]. This length-restricting activity has consequences across cell types: in neurons it controls microtubule growth, dendritic arborization, spine density and synaptic transmission [#3], and in T cells it limits microtubule overgrowth to permit dynein-driven centrosome translocation to the immunological synapse [#8]. As a transporter and scaffold, KIF21B delivers and regulates synaptic receptors and signaling complexes, mediating dendritic delivery of GABAA receptor \\u03b32-subunit vesicles [#2], regulating endocytic recycling of GluN2B-NMDARs within an NBEA\\u2013recycling endosome complex [#6], and sequestering the Rac1-GEF ELMO1 out of spines in an NMDAR-LTD-dependent manner to terminate Rac1 signaling and drive long-term depression [#5]. KIF21B additionally binds and regulates the actin cytoskeleton independently of its motor activity, controlling branching and nucleokinesis during neuronal migration [#10] and, via interactions with GKAP and myosin Va, driving spine actin turnover and GKAP/GluA2-AMPAR removal during homeostatic synaptic downscaling [#11]. Its motility is positively regulated by the E3 ligase TRIM3 through an RBCC-domain interaction without degradation [#1], and neurodevelopmental-disorder-associated missense variants impair neuronal migration by attenuating autoinhibition and producing aberrant excess motor activity [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established that a plus end-directed kinesin could be selectively enriched in dendrites, raising the question of how directional motors achieve compartment-specific localization.\",\n      \"evidence\": \"Immunolocalization in neurons and motor/WD-40 domain analysis\",\n      \"pmids\": [\"10225949\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo bound by the WD-40 domain not identified\", \"Mechanism of dendritic sorting unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified a non-degradative regulator of KIF21B motility, showing motor activity is positively tuned by a binding partner rather than solely intrinsic.\",\n      \"evidence\": \"Co-IP, co-localization at Golgi-derived vesicles, Trim3 knockout mice and motility assays\",\n      \"pmids\": [\"24086586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism by which TRIM3 enhances motility unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Assigned a defined transport cargo to KIF21B, demonstrating it delivers inhibitory receptor vesicles to dendrites and the surface.\",\n      \"evidence\": \"Co-IP, co-localization, shRNA knockdown and surface receptor quantification in neurons\",\n      \"pmids\": [\"25172774\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs adaptor-mediated binding to GABAAR \\u03b32 not resolved\", \"Single lab, two methods\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Revealed that KIF21B is not only a transporter but a regulator of microtubule dynamics whose loss alters dendrite and spine architecture and impairs learning in vivo.\",\n      \"evidence\": \"Kif21b knockout mice, live microtubule imaging, morphology, electrophysiology, behavior\",\n      \"pmids\": [\"27117409\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether dynamics effects are direct or via cargo not separated in vivo\", \"Molecular basis of microtubule regulation not defined here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the biophysical mechanism of KIF21B's microtubule regulation, localizing pause-induction to stalk non-motor and WD40 domains and redefining the autoinhibitory domain's role.\",\n      \"evidence\": \"In vitro reconstitution with purified KIF21B, TIRF microscopy, domain mutagenesis, lattice-binding assays\",\n      \"pmids\": [\"28290984\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How autoinhibition is relieved physiologically not established\", \"Structural basis of GTP-lattice preference unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected KIF21B to activity-dependent synaptic depression by showing it sequesters the Rac1-GEF ELMO1 to terminate Rac1 signaling and drive LTD.\",\n      \"evidence\": \"Kif21b knockout mice, Co-IP, live ELMO1 imaging, fear extinction behavior, CPYPP rescue\",\n      \"pmids\": [\"29949770\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stimulus-dependence of KIF21B-ELMO1 binding mechanism unclear\", \"Link between transport and signaling termination not fully separated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placed KIF21B in an NBEA\\u2013recycling endosome complex controlling GluN2B-NMDAR surface recycling, linking it to social behavior.\",\n      \"evidence\": \"Kif21b knockout mice, Co-IP, live NBEA imaging, surface receptor and social behavior assays\",\n      \"pmids\": [\"29847800\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding partner within complex not pinpointed\", \"Mechanism of recycling control vs transport not separated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed KIF21B acts as an inhibitory constraint on excitatory transmission, distinct from other kinesins.\",\n      \"evidence\": \"RNAi knockdown and whole-cell patch-clamp in hippocampal neurons\",\n      \"pmids\": [\"30479371\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of the constraint not defined\", \"Single method, single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Generalized the length-restricting function beyond neurons, showing KIF21B-induced catastrophe enables centrosome polarization to the immunological synapse in T cells.\",\n      \"evidence\": \"KIF21B knockout T cells, live imaging, vinblastine rescue, biophysical simulations\",\n      \"pmids\": [\"33346730\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the same domains operate in T cells not tested directly\", \"Cargo functions in T cells not addressed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked disease variants to a defined mechanism, showing attenuated autoinhibition produces excess motility that impairs neuronal migration.\",\n      \"evidence\": \"In utero electroporation of patient variants in mouse, migration and axon assays, motor activity measurement\",\n      \"pmids\": [\"32415109\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Named Mendelian disorder not formally defined in timeline\", \"Genotype-phenotype range across variants not fully mapped\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established a motor-independent function for KIF21B in directly binding and regulating actin during neuronal migration.\",\n      \"evidence\": \"In utero electroporation, slice live imaging, in vitro actin binding, in vivo actin dynamics\",\n      \"pmids\": [\"37418324\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Actin-binding domain not mapped\", \"Coordination between actin and microtubule activities unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined a KIF21B\\u2013GKAP\\u2013myosin Va axis controlling spine actin turnover and AMPAR removal during homeostatic downscaling.\",\n      \"evidence\": \"Co-IP, live actin imaging, Kif21b knockout neurons, overexpression, surface receptor assays, chronic activity protocols\",\n      \"pmids\": [\"37418322\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs indirect binding to GKAP/myosin Va not fully resolved\", \"How activity gates spine localization not mechanistically defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Positioned KIF21B downstream of estradiol/BDNF/TrkB signaling in neuritogenesis.\",\n      \"evidence\": \"siRNA knockdown, morphological analysis, TrkB inhibition, Ngn3 expression assays\",\n      \"pmids\": [\"37078090\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting KIF21B to Ngn3 expression unknown\", \"Single lab, correlative pathway placement\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KIF21B's microtubule-regulating, actin-binding, and cargo-transport activities are physiologically coordinated and switched within a single cell remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No integrated structural model of full-length regulation\", \"Triggers that relieve autoinhibition in vivo unknown\", \"Relationship between actin and microtubule functions undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4, 10, 11]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [4, 8, 10]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1, 6]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [3, 5, 6, 7, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [9, 10]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 6]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"complexes\": [\"NBEA\\u2013recycling endosome\\u2013GluN2B-NMDAR complex\"],\n    \"partners\": [\"TRIM3\", \"ELMO1\", \"NBEA\", \"GKAP\", \"MYO5A\", \"GABRG2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}