{"gene":"WDR62","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2010,"finding":"WDR62 protein is enriched in neural progenitors within the ventricular and subventricular zones during embryonic neurogenesis and is predominantly nuclear in localization (unlike other microcephaly genes that associate with centrosomes).","method":"Immunofluorescence and subcellular fractionation in mouse and human embryonic brain tissue","journal":"Nature","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional context, single lab but orthogonal methods (immunostaining + fractionation)","pmids":["20729831"],"is_preprint":false},{"year":2010,"finding":"WDR62 localizes to the spindle poles of dividing cells; missense and frame-shifting mutations in MCPH families cause microcephaly, and WDR62 expression is restricted to neural precursors undergoing mitosis in embryonic brain.","method":"Immunofluorescence in human cell lines and embryonic brain tissue; mutation identification by sequencing","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — spindle pole localization replicated across two independent papers (PMID:20890278, PMID:20890279) with consistent findings","pmids":["20890278","20890279"],"is_preprint":false},{"year":2010,"finding":"Mutant WDR62 proteins failed to localize to the mitotic spindle pole, establishing that spindle pole localization is functionally required and disrupted by MCPH-causing mutations.","method":"Immunofluorescence of endogenous and mutant WDR62 in human cell lines","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiment with functional consequence, replicated across two concurrent independent studies","pmids":["20890279"],"is_preprint":false},{"year":2009,"finding":"WDR62 is a JNK scaffold protein that specifically associates with JNK (but not ERK or p38), potentiates JNK kinase activity, and inhibits AP-1 transcription by sequestering JNK to a non-nuclear (cytoplasmic granular) compartment. Under stress, WDR62 is recruited to stress granules and activated JNK is recruited to processing bodies.","method":"Co-immunoprecipitation, kinase activity assays, overexpression/localization studies in HEK-293T cells, stress granule co-localization","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (co-IP, kinase assay, localization), foundational scaffold characterization replicated in subsequent papers","pmids":["19910486"],"is_preprint":false},{"year":2011,"finding":"WDR62 interacts directly with JNK1, JNK2, and JNK3 through a D-domain motif at its C-terminus; also interacts directly with the JNK-activating kinase MKK7β1 (but not MKK7α1) independently of JNK binding. A synthetic peptide of the WDR62 docking domain inhibits JNK2 activity in vitro. WDR62 association with JNK2 requires both the JNK CD and ED domains.","method":"Co-immunoprecipitation of endogenous and overexpressed proteins, direct protein-protein interaction mapping, in vitro kinase inhibition assay with synthetic peptide","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay plus domain mapping and co-IP, multiple orthogonal methods in one study","pmids":["21749326"],"is_preprint":false},{"year":2014,"finding":"WDR62 associates with Aurora A kinase and genetically interacts with Aurora A to regulate spindle formation and mitotic progression. Wdr62-depleted neural progenitor cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest, and cell death, leading to reduced brain size in mice.","method":"Co-immunoprecipitation, mouse Wdr62 knockout model, genetic interaction analysis, immunofluorescence for spindle markers and SAC components","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP plus genetic epistasis in mouse model with defined cellular phenotype","pmids":["24875059"],"is_preprint":false},{"year":2014,"finding":"WDR62 acts upstream of JNK1 signaling to control neurogenesis; WDR62 knockdown causes premature differentiation of neural progenitor cells (NPCs) with abnormal spindle formation that is rescued by wild-type WDR62 but not by five MCPH-associated WDR62 mutants, and JNK1 depletion phenocopies WDR62 loss.","method":"In utero electroporation knockdown, rescue experiments with WT vs. mutant WDR62, JNK1 depletion in developing cortex","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis (JNK1 knockdown phenocopies WDR62 loss), rescue with WT vs. MCPH mutants, multiple methods","pmids":["24388750"],"is_preprint":false},{"year":2015,"finding":"The WD40-repeat region of WDR62 is required for microtubule association; the disordered C-terminal region regulates cell-cycle-dependent compartmentalization. WDR62 specifically recruits JNK1 (but not JNK2) to the spindle pole. JNK-mediated phosphorylation of WDR62 at T1053 negatively regulates microtubule association (loss of JNK signaling causes constitutive WDR62 localization to microtubules). Aurora A kinase (AURKA) is in complex with WDR62 and AURKA-mediated phosphorylation is required for spindle localization of WDR62 during mitosis.","method":"Domain deletion mapping, phosphorylation site mutagenesis, co-immunoprecipitation, live-cell imaging, kinase assays","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1 / Moderate — phosphorylation site mutagenesis plus co-IP plus domain mapping, multiple orthogonal methods in one study","pmids":["25501809"],"is_preprint":false},{"year":2016,"finding":"WDR62 and ASPM interact physically and co-localize to the proximal end of the mother centriole; WDR62 is required for ASPM localization. Both WDR62 and ASPM are required (along with CEP63) to localize CENPJ/CPAP/Sas-4 to the centriole. Loss of WDR62 or ASPM causes centriole duplication defects and abnormal apical complex localization leading to premature progenitor delamination.","method":"Co-immunoprecipitation, superresolution microscopy, mouse genetic knockouts (single and double), genetic epistasis","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP, multiple knockout combinations for epistasis, superresolution localization, multiple orthogonal methods","pmids":["27974163"],"is_preprint":false},{"year":2016,"finding":"In Drosophila neuroblasts, Wdr62 (CG7337) maintains active interphase microtubule-organizing center (MTOC) activity by stabilizing microtubules, which is necessary for sustained recruitment of Polo/Plk1 to the pericentriolar matrix (PCM) and for downregulation of Pericentrin-like protein (Plp), thereby regulating centrosome asymmetry, spindle orientation, and biased centrosome segregation.","method":"Drosophila genetics, live imaging, immunofluorescence, centrosome marker analysis in wdr62 mutant neuroblasts","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — live imaging plus genetic analysis plus multiple molecular markers, ortholog with consistent biology","pmids":["26804909"],"is_preprint":false},{"year":2017,"finding":"WDR62 interacts with Aurora kinase B (the core enzyme of the chromosome passenger complex, CPC), and this interaction requires wild-type WDR62 (disease-associated mutant forms fail to interact). CPC component staining at centromeres is altered in patient-derived fibroblasts, and asymmetric centrosome inheritance and mitotic progression are defective in patient fibroblasts.","method":"Co-immunoprecipitation of WDR62 with Aurora kinase B, immunofluorescence in patient-derived fibroblasts and mouse neocortical progenitors","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP with WT vs. mutant comparison plus patient cell phenotyping, single lab","pmids":["28272472"],"is_preprint":false},{"year":2017,"finding":"PLK1 phosphorylates WDR62 at Ser897; this phosphorylation at spindle poles promotes astral microtubule assembly and stabilizes mitotic spindle orientation. WDR62/MCPH2 mutant cells exhibit randomized spindle orientation due to impaired astral microtubule assembly.","method":"CRISPR/Cas9 knock-in of WDR62 missense mutation in human cells, PLK1 kinase assay, immunofluorescence for astral microtubules and spindle orientation","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — kinase substrate identification with knock-in cell model, single lab","pmids":["28973348"],"is_preprint":false},{"year":2018,"finding":"WDR62 specifically mediates TNFα-dependent JNK activation through association with both the adaptor protein TRAF2 and the MAP3K protein MLK3 (mixed lineage kinase 3). WDR62 is also responsible for basal c-Jun expression in growing cells. WDR62 knockout cells show increased resistance to TNFα-induced cell death.","method":"CRISPR/Cas9 and shRNA WDR62 knockout in MDA-MB-231 cells, co-immunoprecipitation of WDR62 with TRAF2 and MLK3, JNK activation assays","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP with TRAF2 and MLK3 plus CRISPR knockout with defined signaling readout, single lab","pmids":["30091641"],"is_preprint":false},{"year":2018,"finding":"MEKK3 forms a complex with WDR62 and promotes JNK signaling synergistically. WDR62 protein stability is positively regulated by MEKK3 and JNK1. WDR62 is negatively regulated by T1053 phosphorylation, which recruits FBW7 leading to proteasomal degradation. Deletion of Mekk3, Wdr62, or Jnk1 results in phenocopied premature NPC differentiation defects.","method":"Co-immunoprecipitation, mouse conditional knockouts, transgenic JNK1 rescue, phosphorylation site mutagenesis, proteasome inhibitor experiments","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP plus genetic epistasis (triple phenocopy) plus phosphorylation/degradation mechanism, multiple orthogonal methods","pmids":["30566428"],"is_preprint":false},{"year":2018,"finding":"Wdr62 is required for retinoic acid (RA)-induced Stra8 expression via activation of JNK signaling during female meiotic initiation in mice; defects in meiotic initiation in Wdr62-deficient female mice can be partially rescued by JNK1 overexpression in germ cells.","method":"Mouse Wdr62 knockout, JNK1 overexpression rescue, Stra8 expression analysis","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue experiment (JNK1 overexpression partially rescues WDR62 KO), single lab","pmids":["30102701"],"is_preprint":false},{"year":2019,"finding":"WDR62 interacts with CEP170 and promotes CEP170 localization to the basal body of primary cilia; CEP170 in turn recruits the microtubule-depolymerizing factor KIF2A to disassemble the cilium. WDR62 depletion reduces KIF2A's basal body localization, causing retarded cilium disassembly, elongated cilia, and delayed cell cycle progression in neural progenitors.","method":"Co-immunoprecipitation of WDR62-CEP170 and CEP170-KIF2A, mouse knockout and cerebral organoid models, rescue by enhanced KIF2A expression, immunofluorescence","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP plus genetic rescue plus two independent model systems (mice and organoids), multiple orthogonal methods","pmids":["31197141"],"is_preprint":false},{"year":2019,"finding":"WDR62 interacts with CEP170 in spermatocytes; deletion of Wdr62 causes downregulation of CEP170 protein, leading to aberrant spindle assembly and metaphase I arrest in spermatogenesis.","method":"Co-immunoprecipitation, mouse Wdr62 knockout, immunofluorescence for spindle markers and CEP170","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus knockout phenotype, single lab, consistent with PMID:31197141","pmids":["31533924"],"is_preprint":false},{"year":2019,"finding":"WDR62 co-localizes with chromosomes during mouse oocyte meiotic maturation and is required for asymmetric spindle positioning and actin cap formation. WDR62 depletion disrupts the Arp2/3 complex (an upstream regulator of cortical actin) and blocks asymmetric spindle positioning, causing large polar body extrusion.","method":"siRNA microinjection in mouse oocytes, immunofluorescence for spindle and actin markers, Arp2/3 localization analysis","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with multiple functional readouts, single lab","pmids":["31836472"],"is_preprint":false},{"year":2020,"finding":"WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP; as a consequence, IFT88 (required for cilia formation) is not recruited, leading to deficient ciliogenesis, premature differentiation of radial glia, and cortical thinning.","method":"CRISPR/Cas9 knockin mouse models with patient-derived missense mutations, immunofluorescence for CPAP and IFT88, cilia formation assays","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple knockin mouse models with defined molecular pathway (WDR62→CPAP→IFT88→ciliogenesis), multiple orthogonal methods","pmids":["31816041"],"is_preprint":false},{"year":2021,"finding":"WDR62 localizes katanin to the spindle pole; WDR62 depletion or knockout stabilizes spindle microtubules due to insufficient microtubule minus-end depolymerization, impairs poleward microtubule flux, and causes asynchronous poleward movements in anaphase, leading to lagging chromosomes.","method":"siRNA depletion and CRISPR/Cas9 knockout in human epithelial cells, live-cell imaging, microtubule dynamics assays, immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — both siRNA and CRISPR knockout with live-cell imaging and dynamics measurements, independently reported alongside PMID:34137789","pmids":["34137788"],"is_preprint":false},{"year":2021,"finding":"WDR62 recruits katanin to the spindle pole and functions as an adaptor protein between TPX2/Aurora A (recruiting factor) and katanin (effector). WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. WDR62 shows preference for curved segments of dynamic GDP-MTs. JNK phosphorylation induces autoinhibition of WDR62's MT-binding affinity through intramolecular interaction.","method":"In vitro microtubule binding and severing assays, co-immunoprecipitation, phosphorylation site mutagenesis, in vitro reconstitution with purified proteins","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution plus mutagenesis plus co-IP, multiple orthogonal methods, published concurrently with independent replication (PMID:34137788)","pmids":["34137789"],"is_preprint":false},{"year":2021,"finding":"WDR62 is required for centriole duplication in spermatocytes; WDR62 deficiency causes reduced/delayed CEP63 accumulation in the pericentriolar matrix, centriole underduplication, and prolonged metaphase leading to apoptosis. In spermatids, WDR62 deficiency delays manchette removal due to delayed Katanin p80 accumulation in the manchette.","method":"WDR62 genetrap mouse model, immunofluorescence for centriole and manchette markers, spermatogenesis staging","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetrap knockout with multiple cellular phenotype readouts, single lab","pmids":["34059773"],"is_preprint":false},{"year":2022,"finding":"WDR62 deficiency weakens the association between WDR62 and AURKA on spindle poles, reduces AURKA phosphorylation, and decreases expression of target genes related to cell cycle and spindle assembly shared by WDR62 and AURKA, resulting in cell cycle arrest and multipolar spindles that inhibit cardiomyocyte proliferation.","method":"Co-immunoprecipitation of WDR62 with AURKA, mouse Wdr62 knockout, RNA-seq, immunofluorescence in cardiomyocytes","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus knockout phenotype plus RNA-seq, single lab","pmids":["35808830"],"is_preprint":false},{"year":2022,"finding":"WDR62 depletion in mouse oocytes disrupts meiotic cell cycle progression with metaphase-I arrest, severe spindle abnormality, chromosome misalignment, and aneuploidy; causes defective kinetochore-microtubule attachments and activates the spindle assembly checkpoint (SAC). WDR62 depletion is associated with aberrant p-JNK localization/reduced expression and altered H3K9 trimethylation status.","method":"siRNA microinjection in mouse oocytes, immunofluorescence for spindle/kinetochore markers, SAC markers, JNK inhibitor (SP600125) phenocopy","journal":"The international journal of biochemistry & cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with JNK inhibitor phenocopy, multiple markers, single lab","pmids":["35093571"],"is_preprint":false},{"year":2023,"finding":"WDR62 localizes to the Golgi apparatus during interphase in cultured cells and human fetal brain tissue, and translocates to the mitotic spindle poles in a microtubule-dependent manner. A C-terminal truncating mutation (D955AfsX112) impairs this localization and mitotic progression, and alters neurogenic trajectories in iPSC-derived neural models.","method":"iPSC-derived neural models from patient and isogenic corrected lines, live-cell imaging, immunofluorescence in human fetal brain tissue, microtubule depolymerization experiments","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — human fetal tissue plus iPSC models plus isogenic controls plus live imaging, multiple orthogonal methods","pmids":["37272619"],"is_preprint":false},{"year":2025,"finding":"WDR62 ablation in neural progenitor cells or post-mitotic neurons impedes cortical neuronal radial migration; WDR62 modulates the transition from multipolar to bipolar states in migrating neurons. Levels of Reelin (a key modulator of neuronal migration) are significantly reduced in Wdr62-deficient mouse brains.","method":"In utero electroporation in mice (NPC-specific and post-mitotic neuron-specific ablation), immunofluorescence for migration markers, Western blot for Reelin","journal":"Neurobiology of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in utero electroporation with two cell-type-specific ablations plus Reelin quantification, single lab","pmids":["40349858"],"is_preprint":false},{"year":2026,"finding":"WDR62 interacts directly with BAG2 (a co-chaperone of HSP70/90); under stress, WDR62 and BAG2 re-localize to cytoplasmic granules enriched for purine synthesis (PFAS) and salvage (HPRT) enzymes. In WDR62-deficient cells, purine synthesis is impaired and HPRT is destabilized due to elevated BAG2 levels; BAG2 knockdown restores HPRT levels. Microcephaly-associated WDR62 mutations disrupt BAG2 interaction and fail to restore HPRT levels. In utero depletion of WDR62 or HPRT causes premature delamination and migration of neural precursor cells.","method":"Co-immunoprecipitation, metabolomics/purine assays, BAG2 knockdown rescue, in utero electroporation, microcephaly mutant co-IP","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct binding (co-IP), metabolic functional assays, genetic rescue, in vivo validation, multiple orthogonal methods in one study","pmids":["41787126"],"is_preprint":false},{"year":2026,"finding":"WDR62 deficiency leads to increased centriole numbers and centriole cohesion defects in C2C12 myoblasts, causing decreased myoblast proliferation and premature differentiation. In Drosophila, Wdr62 knockdown in wing disc increases asymmetric myoblast division.","method":"WDR62 knockout in C2C12 myoblasts and mouse models, cardiotoxin injury model, Drosophila wing disc knockdown, centrosome marker immunofluorescence","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple model systems (mouse KO, C2C12, Drosophila) with centrosome phenotyping, single lab","pmids":["41535485"],"is_preprint":false}],"current_model":"WDR62 is a spindle pole- and basal body-associated scaffold protein that (1) regulates mitotic spindle dynamics by recruiting katanin (via a TPX2/Aurora A–WDR62–katanin axis) to depolymerize minus-end microtubules, (2) orchestrates centriole biogenesis and cilium disassembly through sequential recruitment of CEP170 and KIF2A to the basal body, (3) recruits CPAP/CENPJ to the mother centriole (requiring ASPM co-function) to maintain progenitor identity, (4) scaffolds JNK signaling by directly binding all JNK isoforms via a C-terminal D-domain, MKK7β1, MEKK3, and TRAF2/MLK3 to control NPC self-renewal and meiotic initiation, (5) is phospho-regulated by Aurora A (promoting spindle localization), JNK (inhibiting microtubule binding at T1053, triggering FBW7-mediated degradation), and PLK1 (Ser897, promoting astral microtubule assembly), (6) translocates from the Golgi during interphase to spindle poles in mitosis in a microtubule-dependent manner, and (7) supports purine metabolism by interacting with the HSP70/90 co-chaperone BAG2 to stabilize HPRT, with disease-associated mutations disrupting this interaction and impairing purine homeostasis in neural progenitors."},"narrative":{"mechanistic_narrative":"WDR62 is a microcephaly-associated scaffold protein that couples mitotic spindle architecture, centriole/cilium dynamics, and stress-responsive JNK signaling to control the proliferation and identity of neural progenitors [PMID:20890278, PMID:20890279, PMID:24388750, PMID:27974163]. Biallelic and missense mutations in WDR62 cause autosomal-recessive primary microcephaly (MCPH2), and disease-causing mutants fail to localize to the mitotic spindle pole, establishing spindle pole targeting as functionally essential [PMID:20890278, PMID:20890279]. During interphase WDR62 resides at the Golgi and translocates to spindle poles in mitosis in a microtubule-dependent manner [PMID:37272619]; its WD40 repeats mediate microtubule association while a disordered C-terminus controls cell-cycle compartmentalization [PMID:25501809]. At spindle poles WDR62 acts as an adaptor that links TPX2/Aurora A to the microtubule-severing enzyme katanin, promoting minus-end depolymerization and poleward microtubule flux, with loss causing over-stabilized spindles and lagging chromosomes [PMID:34137788, PMID:34137789]. Its activity is phospho-regulated: Aurora A promotes spindle localization, PLK1 phosphorylation at Ser897 drives astral microtubule assembly and correct spindle orientation, and JNK phosphorylation at T1053 inhibits microtubule binding and recruits FBW7 to trigger proteasomal degradation [PMID:25501809, PMID:28973348, PMID:30566428, PMID:34137789]. Independently, WDR62 is a JNK scaffold that binds all three JNK isoforms through a C-terminal D-domain and assembles upstream activators (MKK7β1, MEKK3, TRAF2/MLK3) to control JNK output, neural progenitor self-renewal, and meiotic initiation [PMID:19910486, PMID:21749326, PMID:30091641, PMID:30566428]. At the centriole WDR62 cooperates with ASPM to recruit CPAP/CENPJ and recruits CEP170 to drive KIF2A-dependent cilium disassembly, linking centriole biogenesis and ciliogenesis to timely progenitor cell-cycle progression [PMID:27974163, PMID:31197141, PMID:31816041]. WDR62 additionally supports neuronal radial migration and, through direct interaction with the co-chaperone BAG2, stabilizes the purine-salvage enzyme HPRT to maintain purine homeostasis in neural precursors, a function disrupted by microcephaly mutations [PMID:40349858, PMID:41787126].","teleology":[{"year":2009,"claim":"Before any link to brain development, WDR62 was defined biochemically as a JNK-specific scaffold, establishing its first molecular activity.","evidence":"Co-IP, kinase assays, and stress-granule localization in HEK-293T cells","pmids":["19910486"],"confidence":"High","gaps":["Did not identify the JNK-binding motif","Did not connect scaffolding to a developmental phenotype"]},{"year":2010,"claim":"Identification of WDR62 mutations in microcephaly families and its spindle-pole/neural-progenitor localization established WDR62 as a microcephaly gene acting in dividing neural precursors.","evidence":"Mutation sequencing plus immunofluorescence/fractionation in human and mouse embryonic brain and cell lines","pmids":["20729831","20890278","20890279"],"confidence":"High","gaps":["Conflicting nuclear vs spindle-pole localization not reconciled","Mechanism linking spindle role to microcephaly unresolved"]},{"year":2011,"claim":"Mapping the C-terminal D-domain that binds JNK1/2/3 and direct binding to MKK7β1 defined how WDR62 physically assembles a JNK signaling module.","evidence":"Co-IP, domain mapping, and in vitro kinase inhibition with a synthetic docking peptide","pmids":["21749326"],"confidence":"High","gaps":["Did not link the docking module to spindle function","In vivo relevance not yet shown"]},{"year":2014,"claim":"Genetic and physical coupling to Aurora A, and epistasis with JNK1 in progenitors, connected WDR62's spindle role and its signaling role to neurogenesis.","evidence":"Reciprocal co-IP, mouse knockout, in utero electroporation rescue with WT vs MCPH mutants, JNK1 depletion phenocopy","pmids":["24875059","24388750"],"confidence":"High","gaps":["How Aurora A binding affects WDR62 at the molecular level not defined","Whether JNK and spindle functions are separable unclear"]},{"year":2015,"claim":"Domain and phospho-site dissection showed WD40 repeats mediate microtubule binding while Aurora A and JNK phosphorylation oppositely tune spindle targeting, defining the regulatory logic of WDR62 localization.","evidence":"Domain deletion, T1053 mutagenesis, co-IP, live-cell imaging, kinase assays","pmids":["25501809"],"confidence":"High","gaps":["Downstream microtubule effector at the pole not identified","Mechanism of JNK-dependent compartment switch unresolved"]},{"year":2016,"claim":"WDR62 was placed in the centriole-duplication pathway by showing it cooperates with ASPM and CEP63 to recruit CPAP/CENPJ to the mother centriole.","evidence":"Reciprocal co-IP, superresolution microscopy, single and double mouse knockouts with epistasis","pmids":["27974163"],"confidence":"High","gaps":["Order of recruitment among ASPM/CEP63/CPAP not fully resolved","Direct vs indirect CPAP recruitment unclear"]},{"year":2016,"claim":"Drosophila work established a conserved role in maintaining interphase MTOC activity and centrosome asymmetry via Polo/Plk1 and Plp regulation.","evidence":"Drosophila genetics, live imaging, centrosome marker analysis in wdr62 mutant neuroblasts","pmids":["26804909"],"confidence":"High","gaps":["Whether the mammalian protein regulates Plk1 recruitment identically not shown here","Molecular link to Plp downregulation undefined"]},{"year":2017,"claim":"Identification of an Aurora B/CPC interaction and PLK1-mediated Ser897 phosphorylation extended WDR62's mitotic regulation to astral microtubule assembly and spindle orientation.","evidence":"Co-IP, patient fibroblast phenotyping, PLK1 kinase assay, CRISPR knock-in of an MCPH missense mutation","pmids":["28272472","28973348"],"confidence":"Medium","gaps":["Aurora B interaction not reconstituted in vitro","Relationship between PLK1 and Aurora A inputs not integrated"]},{"year":2018,"claim":"WDR62 was shown to scaffold a TNFα-responsive JNK activation module (TRAF2/MLK3, MEKK3) and to be reciprocally stabilized by that signaling, with T1053-dependent FBW7 degradation completing a feedback loop controlling progenitor differentiation and meiotic initiation.","evidence":"CRISPR/shRNA knockout, co-IP with TRAF2/MLK3/MEKK3, mouse conditional knockouts, phospho/degradation assays, JNK1 rescue of meiosis","pmids":["30091641","30566428","30102701"],"confidence":"High","gaps":["Stoichiometry of the multi-kinase scaffold unknown","How spindle pool and signaling pool of WDR62 are partitioned unclear"]},{"year":2019,"claim":"WDR62 was placed at the basal body controlling cilium disassembly by recruiting CEP170 and thereby KIF2A, linking ciliary dynamics to progenitor cell-cycle progression across cilia and meiotic spindle contexts.","evidence":"Co-IP, mouse knockout and cerebral organoid models, KIF2A rescue, oocyte siRNA with Arp2/3 analysis, spermatocyte knockout","pmids":["31197141","31533924","31836472"],"confidence":"High","gaps":["Whether CEP170 recruitment is direct not established","Link between ciliary and spindle functions of WDR62 unresolved"]},{"year":2020,"claim":"Patient-mutation knock-in mice showed specific MCPH mutants reach the basal body but fail to recruit CPAP and IFT88, defining a separation-of-function mechanism for ciliogenesis defects.","evidence":"CRISPR knock-in mouse models, immunofluorescence for CPAP/IFT88, cilia assays","pmids":["31816041"],"confidence":"High","gaps":["Why these mutants localize but fail to recruit cargo not structurally explained","Relative contributions of cilia vs spindle defects to microcephaly unquantified"]},{"year":2021,"claim":"In vitro reconstitution defined WDR62 as the adaptor that bridges TPX2/Aurora A to katanin to drive minus-end microtubule severing, mechanistically explaining spindle over-stabilization upon loss.","evidence":"siRNA/CRISPR knockout with live imaging and microtubule dynamics, plus in vitro reconstitution, severing assays, and phospho-mutagenesis","pmids":["34137788","34137789"],"confidence":"High","gaps":["How JNK-induced autoinhibition is relieved at the pole not defined","Connection of katanin axis to microcephaly mutations not directly tested"]},{"year":2022,"claim":"Extension to non-neural mitotic tissues (cardiomyocytes, spermatocytes, oocytes) generalized the WDR62–Aurora A spindle-assembly axis as a broad regulator of proliferation and faithful chromosome segregation.","evidence":"Co-IP, knockouts, RNA-seq, oocyte siRNA with SAC and JNK readouts, centriole/manchette phenotyping","pmids":["35808830","35093571","34059773"],"confidence":"Medium","gaps":["Tissue-specific vs core mechanisms not separated","Direct transcriptional vs indirect effects on cell-cycle genes unclear"]},{"year":2023,"claim":"Human iPSC and fetal-tissue models showed WDR62 shuttles from Golgi to spindle poles microtubule-dependently and that truncating mutations alter neurogenic trajectories, anchoring the mechanism in human cells.","evidence":"iPSC neural models with isogenic correction, live imaging, fetal brain immunofluorescence, microtubule depolymerization","pmids":["37272619"],"confidence":"High","gaps":["Functional significance of the Golgi pool undefined","How truncation alters trajectories mechanistically not resolved"]},{"year":2025,"claim":"WDR62 was shown to act beyond mitosis in post-mitotic neurons, controlling multipolar-to-bipolar transition and radial migration with reduced Reelin in deficient brains.","evidence":"In utero electroporation with NPC- and neuron-specific ablation, migration markers, Reelin Western blot","pmids":["40349858"],"confidence":"Medium","gaps":["Whether the migration role is independent of the spindle/centriole function unclear","Mechanism linking WDR62 to Reelin levels unknown"]},{"year":2026,"claim":"A metabolic function was uncovered: WDR62 binds BAG2 to stabilize HPRT and sustain purine homeostasis, with microcephaly mutations disrupting this interaction, adding a chaperone/metabolic arm to its progenitor role.","evidence":"Co-IP, purine metabolomics, BAG2 knockdown rescue, mutant co-IP, in utero depletion of WDR62 or HPRT; plus myoblast/Drosophila centriole-cohesion phenotyping","pmids":["41787126","41535485"],"confidence":"High","gaps":["How a spindle/centriole scaffold also acts in purine metabolism mechanistically unclear","Whether metabolic and cytoskeletal defects contribute independently to microcephaly untested"]},{"year":null,"claim":"It remains unresolved how WDR62's distinct pools (Golgi, spindle pole, basal body, stress granule/chaperone) are partitioned and which functions are primary drivers of microcephaly.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model integrating spindle, ciliary, signaling, and metabolic roles","No structural basis for how phosphorylation switches between functional pools","Relative phenotypic weight of each axis in human disease unquantified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,4,20]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[7,19,20]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,4,20]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1,2,19,20]},{"term_id":"GO:0005794","term_label":"Golgi 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cycle.","date":"2025","source":"Hereditas","url":"https://pubmed.ncbi.nlm.nih.gov/40369663","citation_count":0,"is_preprint":false},{"pmid":"41535485","id":"PMC_41535485","title":"WDR62 is required for proper proliferation and early differentiation of skeletal myoblasts.","date":"2026","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/41535485","citation_count":0,"is_preprint":false},{"pmid":"41787126","id":"PMC_41787126","title":"Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2.","date":"2026","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/41787126","citation_count":0,"is_preprint":false},{"pmid":"42002830","id":"PMC_42002830","title":"Prenatal Diagnosis of Autosomal Recessive Primary Microcephaly Type 2 Caused by Compound Heterozygous WDR62 Variants in a Family With Two Recurrent Cases.","date":"2026","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/42002830","citation_count":0,"is_preprint":false},{"pmid":"40350396","id":"PMC_40350396","title":"[A case of primary microcephaly associated with compound heterozygous variants of WDR62 gene].","date":"2025","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40350396","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.07.01.601630","title":"The microcephaly protein WDR62 regulates cellular purine metabolism through the HSP70/HSP90 chaperone machinery","date":"2024-07-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.01.601630","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":33452,"output_tokens":7123,"usd":0.1036,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":16108,"output_tokens":5417,"usd":0.107982,"stage2_stop_reason":"end_turn"},"total_usd":0.211582,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"WDR62 protein is enriched in neural progenitors within the ventricular and subventricular zones during embryonic neurogenesis and is predominantly nuclear in localization (unlike other microcephaly genes that associate with centrosomes).\",\n      \"method\": \"Immunofluorescence and subcellular fractionation in mouse and human embryonic brain tissue\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional context, single lab but orthogonal methods (immunostaining + fractionation)\",\n      \"pmids\": [\"20729831\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"WDR62 localizes to the spindle poles of dividing cells; missense and frame-shifting mutations in MCPH families cause microcephaly, and WDR62 expression is restricted to neural precursors undergoing mitosis in embryonic brain.\",\n      \"method\": \"Immunofluorescence in human cell lines and embryonic brain tissue; mutation identification by sequencing\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — spindle pole localization replicated across two independent papers (PMID:20890278, PMID:20890279) with consistent findings\",\n      \"pmids\": [\"20890278\", \"20890279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Mutant WDR62 proteins failed to localize to the mitotic spindle pole, establishing that spindle pole localization is functionally required and disrupted by MCPH-causing mutations.\",\n      \"method\": \"Immunofluorescence of endogenous and mutant WDR62 in human cell lines\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiment with functional consequence, replicated across two concurrent independent studies\",\n      \"pmids\": [\"20890279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"WDR62 is a JNK scaffold protein that specifically associates with JNK (but not ERK or p38), potentiates JNK kinase activity, and inhibits AP-1 transcription by sequestering JNK to a non-nuclear (cytoplasmic granular) compartment. Under stress, WDR62 is recruited to stress granules and activated JNK is recruited to processing bodies.\",\n      \"method\": \"Co-immunoprecipitation, kinase activity assays, overexpression/localization studies in HEK-293T cells, stress granule co-localization\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (co-IP, kinase assay, localization), foundational scaffold characterization replicated in subsequent papers\",\n      \"pmids\": [\"19910486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"WDR62 interacts directly with JNK1, JNK2, and JNK3 through a D-domain motif at its C-terminus; also interacts directly with the JNK-activating kinase MKK7β1 (but not MKK7α1) independently of JNK binding. A synthetic peptide of the WDR62 docking domain inhibits JNK2 activity in vitro. WDR62 association with JNK2 requires both the JNK CD and ED domains.\",\n      \"method\": \"Co-immunoprecipitation of endogenous and overexpressed proteins, direct protein-protein interaction mapping, in vitro kinase inhibition assay with synthetic peptide\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay plus domain mapping and co-IP, multiple orthogonal methods in one study\",\n      \"pmids\": [\"21749326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"WDR62 associates with Aurora A kinase and genetically interacts with Aurora A to regulate spindle formation and mitotic progression. Wdr62-depleted neural progenitor cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest, and cell death, leading to reduced brain size in mice.\",\n      \"method\": \"Co-immunoprecipitation, mouse Wdr62 knockout model, genetic interaction analysis, immunofluorescence for spindle markers and SAC components\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP plus genetic epistasis in mouse model with defined cellular phenotype\",\n      \"pmids\": [\"24875059\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"WDR62 acts upstream of JNK1 signaling to control neurogenesis; WDR62 knockdown causes premature differentiation of neural progenitor cells (NPCs) with abnormal spindle formation that is rescued by wild-type WDR62 but not by five MCPH-associated WDR62 mutants, and JNK1 depletion phenocopies WDR62 loss.\",\n      \"method\": \"In utero electroporation knockdown, rescue experiments with WT vs. mutant WDR62, JNK1 depletion in developing cortex\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis (JNK1 knockdown phenocopies WDR62 loss), rescue with WT vs. MCPH mutants, multiple methods\",\n      \"pmids\": [\"24388750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The WD40-repeat region of WDR62 is required for microtubule association; the disordered C-terminal region regulates cell-cycle-dependent compartmentalization. WDR62 specifically recruits JNK1 (but not JNK2) to the spindle pole. JNK-mediated phosphorylation of WDR62 at T1053 negatively regulates microtubule association (loss of JNK signaling causes constitutive WDR62 localization to microtubules). Aurora A kinase (AURKA) is in complex with WDR62 and AURKA-mediated phosphorylation is required for spindle localization of WDR62 during mitosis.\",\n      \"method\": \"Domain deletion mapping, phosphorylation site mutagenesis, co-immunoprecipitation, live-cell imaging, kinase assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — phosphorylation site mutagenesis plus co-IP plus domain mapping, multiple orthogonal methods in one study\",\n      \"pmids\": [\"25501809\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"WDR62 and ASPM interact physically and co-localize to the proximal end of the mother centriole; WDR62 is required for ASPM localization. Both WDR62 and ASPM are required (along with CEP63) to localize CENPJ/CPAP/Sas-4 to the centriole. Loss of WDR62 or ASPM causes centriole duplication defects and abnormal apical complex localization leading to premature progenitor delamination.\",\n      \"method\": \"Co-immunoprecipitation, superresolution microscopy, mouse genetic knockouts (single and double), genetic epistasis\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP, multiple knockout combinations for epistasis, superresolution localization, multiple orthogonal methods\",\n      \"pmids\": [\"27974163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In Drosophila neuroblasts, Wdr62 (CG7337) maintains active interphase microtubule-organizing center (MTOC) activity by stabilizing microtubules, which is necessary for sustained recruitment of Polo/Plk1 to the pericentriolar matrix (PCM) and for downregulation of Pericentrin-like protein (Plp), thereby regulating centrosome asymmetry, spindle orientation, and biased centrosome segregation.\",\n      \"method\": \"Drosophila genetics, live imaging, immunofluorescence, centrosome marker analysis in wdr62 mutant neuroblasts\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — live imaging plus genetic analysis plus multiple molecular markers, ortholog with consistent biology\",\n      \"pmids\": [\"26804909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"WDR62 interacts with Aurora kinase B (the core enzyme of the chromosome passenger complex, CPC), and this interaction requires wild-type WDR62 (disease-associated mutant forms fail to interact). CPC component staining at centromeres is altered in patient-derived fibroblasts, and asymmetric centrosome inheritance and mitotic progression are defective in patient fibroblasts.\",\n      \"method\": \"Co-immunoprecipitation of WDR62 with Aurora kinase B, immunofluorescence in patient-derived fibroblasts and mouse neocortical progenitors\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP with WT vs. mutant comparison plus patient cell phenotyping, single lab\",\n      \"pmids\": [\"28272472\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PLK1 phosphorylates WDR62 at Ser897; this phosphorylation at spindle poles promotes astral microtubule assembly and stabilizes mitotic spindle orientation. WDR62/MCPH2 mutant cells exhibit randomized spindle orientation due to impaired astral microtubule assembly.\",\n      \"method\": \"CRISPR/Cas9 knock-in of WDR62 missense mutation in human cells, PLK1 kinase assay, immunofluorescence for astral microtubules and spindle orientation\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — kinase substrate identification with knock-in cell model, single lab\",\n      \"pmids\": [\"28973348\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"WDR62 specifically mediates TNFα-dependent JNK activation through association with both the adaptor protein TRAF2 and the MAP3K protein MLK3 (mixed lineage kinase 3). WDR62 is also responsible for basal c-Jun expression in growing cells. WDR62 knockout cells show increased resistance to TNFα-induced cell death.\",\n      \"method\": \"CRISPR/Cas9 and shRNA WDR62 knockout in MDA-MB-231 cells, co-immunoprecipitation of WDR62 with TRAF2 and MLK3, JNK activation assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP with TRAF2 and MLK3 plus CRISPR knockout with defined signaling readout, single lab\",\n      \"pmids\": [\"30091641\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MEKK3 forms a complex with WDR62 and promotes JNK signaling synergistically. WDR62 protein stability is positively regulated by MEKK3 and JNK1. WDR62 is negatively regulated by T1053 phosphorylation, which recruits FBW7 leading to proteasomal degradation. Deletion of Mekk3, Wdr62, or Jnk1 results in phenocopied premature NPC differentiation defects.\",\n      \"method\": \"Co-immunoprecipitation, mouse conditional knockouts, transgenic JNK1 rescue, phosphorylation site mutagenesis, proteasome inhibitor experiments\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP plus genetic epistasis (triple phenocopy) plus phosphorylation/degradation mechanism, multiple orthogonal methods\",\n      \"pmids\": [\"30566428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Wdr62 is required for retinoic acid (RA)-induced Stra8 expression via activation of JNK signaling during female meiotic initiation in mice; defects in meiotic initiation in Wdr62-deficient female mice can be partially rescued by JNK1 overexpression in germ cells.\",\n      \"method\": \"Mouse Wdr62 knockout, JNK1 overexpression rescue, Stra8 expression analysis\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue experiment (JNK1 overexpression partially rescues WDR62 KO), single lab\",\n      \"pmids\": [\"30102701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR62 interacts with CEP170 and promotes CEP170 localization to the basal body of primary cilia; CEP170 in turn recruits the microtubule-depolymerizing factor KIF2A to disassemble the cilium. WDR62 depletion reduces KIF2A's basal body localization, causing retarded cilium disassembly, elongated cilia, and delayed cell cycle progression in neural progenitors.\",\n      \"method\": \"Co-immunoprecipitation of WDR62-CEP170 and CEP170-KIF2A, mouse knockout and cerebral organoid models, rescue by enhanced KIF2A expression, immunofluorescence\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP plus genetic rescue plus two independent model systems (mice and organoids), multiple orthogonal methods\",\n      \"pmids\": [\"31197141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR62 interacts with CEP170 in spermatocytes; deletion of Wdr62 causes downregulation of CEP170 protein, leading to aberrant spindle assembly and metaphase I arrest in spermatogenesis.\",\n      \"method\": \"Co-immunoprecipitation, mouse Wdr62 knockout, immunofluorescence for spindle markers and CEP170\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus knockout phenotype, single lab, consistent with PMID:31197141\",\n      \"pmids\": [\"31533924\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR62 co-localizes with chromosomes during mouse oocyte meiotic maturation and is required for asymmetric spindle positioning and actin cap formation. WDR62 depletion disrupts the Arp2/3 complex (an upstream regulator of cortical actin) and blocks asymmetric spindle positioning, causing large polar body extrusion.\",\n      \"method\": \"siRNA microinjection in mouse oocytes, immunofluorescence for spindle and actin markers, Arp2/3 localization analysis\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with multiple functional readouts, single lab\",\n      \"pmids\": [\"31836472\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP; as a consequence, IFT88 (required for cilia formation) is not recruited, leading to deficient ciliogenesis, premature differentiation of radial glia, and cortical thinning.\",\n      \"method\": \"CRISPR/Cas9 knockin mouse models with patient-derived missense mutations, immunofluorescence for CPAP and IFT88, cilia formation assays\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple knockin mouse models with defined molecular pathway (WDR62→CPAP→IFT88→ciliogenesis), multiple orthogonal methods\",\n      \"pmids\": [\"31816041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"WDR62 localizes katanin to the spindle pole; WDR62 depletion or knockout stabilizes spindle microtubules due to insufficient microtubule minus-end depolymerization, impairs poleward microtubule flux, and causes asynchronous poleward movements in anaphase, leading to lagging chromosomes.\",\n      \"method\": \"siRNA depletion and CRISPR/Cas9 knockout in human epithelial cells, live-cell imaging, microtubule dynamics assays, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — both siRNA and CRISPR knockout with live-cell imaging and dynamics measurements, independently reported alongside PMID:34137789\",\n      \"pmids\": [\"34137788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"WDR62 recruits katanin to the spindle pole and functions as an adaptor protein between TPX2/Aurora A (recruiting factor) and katanin (effector). WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. WDR62 shows preference for curved segments of dynamic GDP-MTs. JNK phosphorylation induces autoinhibition of WDR62's MT-binding affinity through intramolecular interaction.\",\n      \"method\": \"In vitro microtubule binding and severing assays, co-immunoprecipitation, phosphorylation site mutagenesis, in vitro reconstitution with purified proteins\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution plus mutagenesis plus co-IP, multiple orthogonal methods, published concurrently with independent replication (PMID:34137788)\",\n      \"pmids\": [\"34137789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"WDR62 is required for centriole duplication in spermatocytes; WDR62 deficiency causes reduced/delayed CEP63 accumulation in the pericentriolar matrix, centriole underduplication, and prolonged metaphase leading to apoptosis. In spermatids, WDR62 deficiency delays manchette removal due to delayed Katanin p80 accumulation in the manchette.\",\n      \"method\": \"WDR62 genetrap mouse model, immunofluorescence for centriole and manchette markers, spermatogenesis staging\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetrap knockout with multiple cellular phenotype readouts, single lab\",\n      \"pmids\": [\"34059773\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"WDR62 deficiency weakens the association between WDR62 and AURKA on spindle poles, reduces AURKA phosphorylation, and decreases expression of target genes related to cell cycle and spindle assembly shared by WDR62 and AURKA, resulting in cell cycle arrest and multipolar spindles that inhibit cardiomyocyte proliferation.\",\n      \"method\": \"Co-immunoprecipitation of WDR62 with AURKA, mouse Wdr62 knockout, RNA-seq, immunofluorescence in cardiomyocytes\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus knockout phenotype plus RNA-seq, single lab\",\n      \"pmids\": [\"35808830\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"WDR62 depletion in mouse oocytes disrupts meiotic cell cycle progression with metaphase-I arrest, severe spindle abnormality, chromosome misalignment, and aneuploidy; causes defective kinetochore-microtubule attachments and activates the spindle assembly checkpoint (SAC). WDR62 depletion is associated with aberrant p-JNK localization/reduced expression and altered H3K9 trimethylation status.\",\n      \"method\": \"siRNA microinjection in mouse oocytes, immunofluorescence for spindle/kinetochore markers, SAC markers, JNK inhibitor (SP600125) phenocopy\",\n      \"journal\": \"The international journal of biochemistry & cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with JNK inhibitor phenocopy, multiple markers, single lab\",\n      \"pmids\": [\"35093571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"WDR62 localizes to the Golgi apparatus during interphase in cultured cells and human fetal brain tissue, and translocates to the mitotic spindle poles in a microtubule-dependent manner. A C-terminal truncating mutation (D955AfsX112) impairs this localization and mitotic progression, and alters neurogenic trajectories in iPSC-derived neural models.\",\n      \"method\": \"iPSC-derived neural models from patient and isogenic corrected lines, live-cell imaging, immunofluorescence in human fetal brain tissue, microtubule depolymerization experiments\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — human fetal tissue plus iPSC models plus isogenic controls plus live imaging, multiple orthogonal methods\",\n      \"pmids\": [\"37272619\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"WDR62 ablation in neural progenitor cells or post-mitotic neurons impedes cortical neuronal radial migration; WDR62 modulates the transition from multipolar to bipolar states in migrating neurons. Levels of Reelin (a key modulator of neuronal migration) are significantly reduced in Wdr62-deficient mouse brains.\",\n      \"method\": \"In utero electroporation in mice (NPC-specific and post-mitotic neuron-specific ablation), immunofluorescence for migration markers, Western blot for Reelin\",\n      \"journal\": \"Neurobiology of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in utero electroporation with two cell-type-specific ablations plus Reelin quantification, single lab\",\n      \"pmids\": [\"40349858\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"WDR62 interacts directly with BAG2 (a co-chaperone of HSP70/90); under stress, WDR62 and BAG2 re-localize to cytoplasmic granules enriched for purine synthesis (PFAS) and salvage (HPRT) enzymes. In WDR62-deficient cells, purine synthesis is impaired and HPRT is destabilized due to elevated BAG2 levels; BAG2 knockdown restores HPRT levels. Microcephaly-associated WDR62 mutations disrupt BAG2 interaction and fail to restore HPRT levels. In utero depletion of WDR62 or HPRT causes premature delamination and migration of neural precursor cells.\",\n      \"method\": \"Co-immunoprecipitation, metabolomics/purine assays, BAG2 knockdown rescue, in utero electroporation, microcephaly mutant co-IP\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct binding (co-IP), metabolic functional assays, genetic rescue, in vivo validation, multiple orthogonal methods in one study\",\n      \"pmids\": [\"41787126\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"WDR62 deficiency leads to increased centriole numbers and centriole cohesion defects in C2C12 myoblasts, causing decreased myoblast proliferation and premature differentiation. In Drosophila, Wdr62 knockdown in wing disc increases asymmetric myoblast division.\",\n      \"method\": \"WDR62 knockout in C2C12 myoblasts and mouse models, cardiotoxin injury model, Drosophila wing disc knockdown, centrosome marker immunofluorescence\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple model systems (mouse KO, C2C12, Drosophila) with centrosome phenotyping, single lab\",\n      \"pmids\": [\"41535485\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR62 is a spindle pole- and basal body-associated scaffold protein that (1) regulates mitotic spindle dynamics by recruiting katanin (via a TPX2/Aurora A–WDR62–katanin axis) to depolymerize minus-end microtubules, (2) orchestrates centriole biogenesis and cilium disassembly through sequential recruitment of CEP170 and KIF2A to the basal body, (3) recruits CPAP/CENPJ to the mother centriole (requiring ASPM co-function) to maintain progenitor identity, (4) scaffolds JNK signaling by directly binding all JNK isoforms via a C-terminal D-domain, MKK7β1, MEKK3, and TRAF2/MLK3 to control NPC self-renewal and meiotic initiation, (5) is phospho-regulated by Aurora A (promoting spindle localization), JNK (inhibiting microtubule binding at T1053, triggering FBW7-mediated degradation), and PLK1 (Ser897, promoting astral microtubule assembly), (6) translocates from the Golgi during interphase to spindle poles in mitosis in a microtubule-dependent manner, and (7) supports purine metabolism by interacting with the HSP70/90 co-chaperone BAG2 to stabilize HPRT, with disease-associated mutations disrupting this interaction and impairing purine homeostasis in neural progenitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR62 is a microcephaly-associated scaffold protein that couples mitotic spindle architecture, centriole/cilium dynamics, and stress-responsive JNK signaling to control the proliferation and identity of neural progenitors [#1, #6, #8]. Biallelic and missense mutations in WDR62 cause autosomal-recessive primary microcephaly (MCPH2), and disease-causing mutants fail to localize to the mitotic spindle pole, establishing spindle pole targeting as functionally essential [#1, #2]. During interphase WDR62 resides at the Golgi and translocates to spindle poles in mitosis in a microtubule-dependent manner [#24]; its WD40 repeats mediate microtubule association while a disordered C-terminus controls cell-cycle compartmentalization [#7]. At spindle poles WDR62 acts as an adaptor that links TPX2/Aurora A to the microtubule-severing enzyme katanin, promoting minus-end depolymerization and poleward microtubule flux, with loss causing over-stabilized spindles and lagging chromosomes [#19, #20]. Its activity is phospho-regulated: Aurora A promotes spindle localization, PLK1 phosphorylation at Ser897 drives astral microtubule assembly and correct spindle orientation, and JNK phosphorylation at T1053 inhibits microtubule binding and recruits FBW7 to trigger proteasomal degradation [#7, #11, #13, #20]. Independently, WDR62 is a JNK scaffold that binds all three JNK isoforms through a C-terminal D-domain and assembles upstream activators (MKK7β1, MEKK3, TRAF2/MLK3) to control JNK output, neural progenitor self-renewal, and meiotic initiation [#3, #4, #12, #13]. At the centriole WDR62 cooperates with ASPM to recruit CPAP/CENPJ and recruits CEP170 to drive KIF2A-dependent cilium disassembly, linking centriole biogenesis and ciliogenesis to timely progenitor cell-cycle progression [#8, #15, #18]. WDR62 additionally supports neuronal radial migration and, through direct interaction with the co-chaperone BAG2, stabilizes the purine-salvage enzyme HPRT to maintain purine homeostasis in neural precursors, a function disrupted by microcephaly mutations [#25, #26].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before any link to brain development, WDR62 was defined biochemically as a JNK-specific scaffold, establishing its first molecular activity.\",\n      \"evidence\": \"Co-IP, kinase assays, and stress-granule localization in HEK-293T cells\",\n      \"pmids\": [\"19910486\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the JNK-binding motif\", \"Did not connect scaffolding to a developmental phenotype\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identification of WDR62 mutations in microcephaly families and its spindle-pole/neural-progenitor localization established WDR62 as a microcephaly gene acting in dividing neural precursors.\",\n      \"evidence\": \"Mutation sequencing plus immunofluorescence/fractionation in human and mouse embryonic brain and cell lines\",\n      \"pmids\": [\"20729831\", \"20890278\", \"20890279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conflicting nuclear vs spindle-pole localization not reconciled\", \"Mechanism linking spindle role to microcephaly unresolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Mapping the C-terminal D-domain that binds JNK1/2/3 and direct binding to MKK7β1 defined how WDR62 physically assembles a JNK signaling module.\",\n      \"evidence\": \"Co-IP, domain mapping, and in vitro kinase inhibition with a synthetic docking peptide\",\n      \"pmids\": [\"21749326\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not link the docking module to spindle function\", \"In vivo relevance not yet shown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Genetic and physical coupling to Aurora A, and epistasis with JNK1 in progenitors, connected WDR62's spindle role and its signaling role to neurogenesis.\",\n      \"evidence\": \"Reciprocal co-IP, mouse knockout, in utero electroporation rescue with WT vs MCPH mutants, JNK1 depletion phenocopy\",\n      \"pmids\": [\"24875059\", \"24388750\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How Aurora A binding affects WDR62 at the molecular level not defined\", \"Whether JNK and spindle functions are separable unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Domain and phospho-site dissection showed WD40 repeats mediate microtubule binding while Aurora A and JNK phosphorylation oppositely tune spindle targeting, defining the regulatory logic of WDR62 localization.\",\n      \"evidence\": \"Domain deletion, T1053 mutagenesis, co-IP, live-cell imaging, kinase assays\",\n      \"pmids\": [\"25501809\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream microtubule effector at the pole not identified\", \"Mechanism of JNK-dependent compartment switch unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"WDR62 was placed in the centriole-duplication pathway by showing it cooperates with ASPM and CEP63 to recruit CPAP/CENPJ to the mother centriole.\",\n      \"evidence\": \"Reciprocal co-IP, superresolution microscopy, single and double mouse knockouts with epistasis\",\n      \"pmids\": [\"27974163\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Order of recruitment among ASPM/CEP63/CPAP not fully resolved\", \"Direct vs indirect CPAP recruitment unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Drosophila work established a conserved role in maintaining interphase MTOC activity and centrosome asymmetry via Polo/Plk1 and Plp regulation.\",\n      \"evidence\": \"Drosophila genetics, live imaging, centrosome marker analysis in wdr62 mutant neuroblasts\",\n      \"pmids\": [\"26804909\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the mammalian protein regulates Plk1 recruitment identically not shown here\", \"Molecular link to Plp downregulation undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identification of an Aurora B/CPC interaction and PLK1-mediated Ser897 phosphorylation extended WDR62's mitotic regulation to astral microtubule assembly and spindle orientation.\",\n      \"evidence\": \"Co-IP, patient fibroblast phenotyping, PLK1 kinase assay, CRISPR knock-in of an MCPH missense mutation\",\n      \"pmids\": [\"28272472\", \"28973348\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Aurora B interaction not reconstituted in vitro\", \"Relationship between PLK1 and Aurora A inputs not integrated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"WDR62 was shown to scaffold a TNFα-responsive JNK activation module (TRAF2/MLK3, MEKK3) and to be reciprocally stabilized by that signaling, with T1053-dependent FBW7 degradation completing a feedback loop controlling progenitor differentiation and meiotic initiation.\",\n      \"evidence\": \"CRISPR/shRNA knockout, co-IP with TRAF2/MLK3/MEKK3, mouse conditional knockouts, phospho/degradation assays, JNK1 rescue of meiosis\",\n      \"pmids\": [\"30091641\", \"30566428\", \"30102701\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the multi-kinase scaffold unknown\", \"How spindle pool and signaling pool of WDR62 are partitioned unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"WDR62 was placed at the basal body controlling cilium disassembly by recruiting CEP170 and thereby KIF2A, linking ciliary dynamics to progenitor cell-cycle progression across cilia and meiotic spindle contexts.\",\n      \"evidence\": \"Co-IP, mouse knockout and cerebral organoid models, KIF2A rescue, oocyte siRNA with Arp2/3 analysis, spermatocyte knockout\",\n      \"pmids\": [\"31197141\", \"31533924\", \"31836472\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CEP170 recruitment is direct not established\", \"Link between ciliary and spindle functions of WDR62 unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Patient-mutation knock-in mice showed specific MCPH mutants reach the basal body but fail to recruit CPAP and IFT88, defining a separation-of-function mechanism for ciliogenesis defects.\",\n      \"evidence\": \"CRISPR knock-in mouse models, immunofluorescence for CPAP/IFT88, cilia assays\",\n      \"pmids\": [\"31816041\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why these mutants localize but fail to recruit cargo not structurally explained\", \"Relative contributions of cilia vs spindle defects to microcephaly unquantified\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"In vitro reconstitution defined WDR62 as the adaptor that bridges TPX2/Aurora A to katanin to drive minus-end microtubule severing, mechanistically explaining spindle over-stabilization upon loss.\",\n      \"evidence\": \"siRNA/CRISPR knockout with live imaging and microtubule dynamics, plus in vitro reconstitution, severing assays, and phospho-mutagenesis\",\n      \"pmids\": [\"34137788\", \"34137789\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How JNK-induced autoinhibition is relieved at the pole not defined\", \"Connection of katanin axis to microcephaly mutations not directly tested\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extension to non-neural mitotic tissues (cardiomyocytes, spermatocytes, oocytes) generalized the WDR62–Aurora A spindle-assembly axis as a broad regulator of proliferation and faithful chromosome segregation.\",\n      \"evidence\": \"Co-IP, knockouts, RNA-seq, oocyte siRNA with SAC and JNK readouts, centriole/manchette phenotyping\",\n      \"pmids\": [\"35808830\", \"35093571\", \"34059773\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Tissue-specific vs core mechanisms not separated\", \"Direct transcriptional vs indirect effects on cell-cycle genes unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Human iPSC and fetal-tissue models showed WDR62 shuttles from Golgi to spindle poles microtubule-dependently and that truncating mutations alter neurogenic trajectories, anchoring the mechanism in human cells.\",\n      \"evidence\": \"iPSC neural models with isogenic correction, live imaging, fetal brain immunofluorescence, microtubule depolymerization\",\n      \"pmids\": [\"37272619\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional significance of the Golgi pool undefined\", \"How truncation alters trajectories mechanistically not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"WDR62 was shown to act beyond mitosis in post-mitotic neurons, controlling multipolar-to-bipolar transition and radial migration with reduced Reelin in deficient brains.\",\n      \"evidence\": \"In utero electroporation with NPC- and neuron-specific ablation, migration markers, Reelin Western blot\",\n      \"pmids\": [\"40349858\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the migration role is independent of the spindle/centriole function unclear\", \"Mechanism linking WDR62 to Reelin levels unknown\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"A metabolic function was uncovered: WDR62 binds BAG2 to stabilize HPRT and sustain purine homeostasis, with microcephaly mutations disrupting this interaction, adding a chaperone/metabolic arm to its progenitor role.\",\n      \"evidence\": \"Co-IP, purine metabolomics, BAG2 knockdown rescue, mutant co-IP, in utero depletion of WDR62 or HPRT; plus myoblast/Drosophila centriole-cohesion phenotyping\",\n      \"pmids\": [\"41787126\", \"41535485\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How a spindle/centriole scaffold also acts in purine metabolism mechanistically unclear\", \"Whether metabolic and cytoskeletal defects contribute independently to microcephaly untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how WDR62's distinct pools (Golgi, spindle pole, basal body, stress granule/chaperone) are partitioned and which functions are primary drivers of microcephaly.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model integrating spindle, ciliary, signaling, and metabolic roles\", \"No structural basis for how phosphorylation switches between functional pools\", \"Relative phenotypic weight of each axis in human disease unquantified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 4, 20]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [7, 19, 20]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 4, 20]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1, 2, 19, 20]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [8, 15, 18]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [24]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [15, 18]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [5, 19, 20]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 4, 12, 13]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [6, 8, 25]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [8, 15, 18]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"AURKA\", \"JNK1\", \"MKK7\", \"MEKK3\", \"TRAF2\", \"ASPM\", \"CEP170\", \"BAG2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}