{"gene":"CEP164","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2007,"finding":"CEP164 localizes to the distal appendages of mature centrioles (mother centriole), as determined by immunogold electron microscopy, and is indispensable for primary cilium formation. Unlike subdistal appendage proteins ninein and Cep170, CEP164 persists at centrioles throughout mitosis, and its localization is mutually independent of ninein/Cep170 during interphase.","method":"siRNA screen, immunogold electron microscopy, immunofluorescence, RNAi knockdown with ciliogenesis phenotype readout","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal localization studies with immunogold EM and functional RNAi knockdown; foundational paper replicated by multiple subsequent studies","pmids":["17954613"],"is_preprint":false},{"year":2008,"finding":"CEP164 (KIAA1052) interacts with both ATR and ATM kinases, is phosphorylated at Ser186 by ATR/ATM in vitro and in vivo upon replication stress, UV, and ionizing radiation, and functions as a mediator in the DNA damage response. MDC1 knockdown severely reduces Ser186 phosphorylation, and CEP164 knockdown diminishes DNA damage-induced phosphorylation of RPA, H2AX, MDC1, CHK2, and CHK1 (but not NBS1), and causes G2/M checkpoint defects.","method":"Co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, phospho-specific antibody analysis, cell cycle checkpoint assays","journal":"Genes & development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro kinase assay plus Co-IP and functional knockdown; single lab, multiple orthogonal methods","pmids":["18283122"],"is_preprint":false},{"year":2009,"finding":"Upon UV irradiation, CEP164 interacts with XPA (Xeroderma pigmentosum group A) in a UV-dependent manner; CEP164 binds to amino acids 4–97 of XPA. XPA is required for recruitment of CEP164 to cyclobutane pyrimidine dimer (CPD) sites. CEP164 knockdown compromises cell survival upon UV damage and impairs UV-induced CHK1 phosphorylation.","method":"Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), immunofluorescence colocalization with CPD, siRNA knockdown, complementation with XPA deletion mutants","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and domain mapping plus functional knockdown and ChIP; single lab, multiple orthogonal methods","pmids":["19197159"],"is_preprint":false},{"year":2012,"finding":"Upon induced DNA damage, CEP164 co-localizes to nuclear foci positive for TIP60 (an ATM activator) together with ZNF423 and NPHP10. CEP164 knockdown causes sensitivity to DNA damaging agents. Zebrafish cep164 knockdown results in dysregulated DDR and a nephronophthisis-related ciliopathy phenotype.","method":"Immunofluorescence colocalization at DNA damage foci, siRNA knockdown with DNA damage sensitivity assays, zebrafish morpholino knockdown","journal":"Cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (colocalization, sensitivity assays, in vivo model), single lab","pmids":["22863007"],"is_preprint":false},{"year":2012,"finding":"CEP164 physically interacts with INPP5E (inositol polyphosphate-5-phosphatase E) and participates in a functional network with ARL13B, INPP5E, and PDE6D for ciliary targeting of INPP5E. This network is distinct from those defined by NPHP and MKS proteins.","method":"Protein-protein interaction assays (pulldown/Co-IP), genetic analysis, ciliary targeting experiments","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP/pulldown interaction data combined with functional ciliary targeting analysis; single lab","pmids":["23150559"],"is_preprint":false},{"year":2014,"finding":"CEP164 recruits TTBK2 (Tau tubulin kinase 2) to the mother centriole to trigger ciliogenesis. CEP164 is a likely physiological substrate of TTBK2. Complex formation between CEP164 and TTBK2 is mediated by mapped interaction domains, and is essential for TTBK2 recruitment to basal bodies. Ciliogenesis can be rescued in CEP164-depleted cells by chimeric proteins fusing TTBK2 to the C-terminal centriole-targeting domain of CEP164. TTBK2 acts upstream of CEP164 to contribute to distal appendage assembly.","method":"Co-immunoprecipitation, domain mapping, siRNA knockdown, chimeric protein rescue, immunofluorescence","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, domain mapping, chimeric rescue experiments, and multiple functional readouts; replicated by independent lab (PMID:25297623)","pmids":["24982133"],"is_preprint":false},{"year":2014,"finding":"CEP164 is essential for TTBK2 centriolar localization via a proline-rich motif on TTBK2 (not via SxIP/EB1 motifs). TTBK2 non-Cep164-binding mutants fail to rescue CP110 removal and ciliogenesis in TTBK2-depleted cells. TTBK2 can phosphorylate CEP164 and Cep97, and TTBK2 kinase activity inhibits the CEP164–Dishevelled-3 interaction.","method":"Co-immunoprecipitation, site-directed mutagenesis of TTBK2 binding motifs, rescue experiments in TTBK2-depleted cells, in vitro phosphorylation assay","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — mutagenesis of binding domain plus functional rescue assays plus in vitro phosphorylation; independent replication of CEP164–TTBK2 complex (consistent with PMID:24982133)","pmids":["25297623"],"is_preprint":false},{"year":2014,"finding":"CEP164 knockdown promotes cells to accumulate in S-phase and causes cell cycle acceleration, apoptosis, and epithelial-to-mesenchymal transition. These effects can be rescued by wild-type CEP164 but not disease-associated CEP164 mutants. Overexpression of dominant-negative CEP164 Q525X also induces EMT and pro-fibrotic gene upregulation.","method":"siRNA knockdown with live-cell imaging (RPE-FUCCI), FACS, CyQuant proliferation assay, immunofluorescence, RT-qPCR, zebrafish morpholino knockdown, rescue with WT vs. mutant CEP164","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (FACS, live imaging, in vivo model, mutant rescue); single lab","pmids":["25340510"],"is_preprint":false},{"year":2016,"finding":"NEGATIVE FINDING: Conditional depletion of CEP164 in DT40 cells (auxin-inducible degron) caused no increase in sensitivity to ionising or UV irradiation. Disruption of CEP164 in human RPE cells blocked primary cilium formation but did not affect proliferation or responses to ionising/UV irradiation. No nuclear localization of CEP164 was detected by immunofluorescence or analysis of multiple tagged forms of CEP164. These data suggest CEP164 is not required for the DNA damage response.","method":"Auxin-inducible degron conditional depletion, genome editing (CRISPR/reverse genetics), clonogenic survival assays, immunofluorescence with multiple tagged CEP164 constructs","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome editing plus multiple tagged constructs and functional assays; single lab but rigorous negative result contradicting earlier DDR claims","pmids":["26966185"],"is_preprint":false},{"year":2017,"finding":"CEP164 is required for multiciliogenesis via regulation of small vesicle recruitment, ciliary vesicle formation, and basal body docking. CEP164 is necessary for proper recruitment of Chibby1 (Cby1) and its binding partners FAM92A and FAM92B to the ciliary base in multiciliated cells. CEP164 controls ciliary targeting of membrane-associated proteins including Rab8, Rab11, and Arl13b. Unlike in primary ciliogenesis, CEP164 is dispensable for IFT component recruitment to multicilia.","method":"Conditional knockout mouse model (FoxJ1-Cre;CEP164fl/fl), primary tracheal multiciliated cell cultures, immunofluorescence, electron microscopy","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO mouse with multiple tissue readouts and primary cell cultures; multiple orthogonal methods (EM, IF, in vivo); single lab but rigorous and comprehensive","pmids":["29244804"],"is_preprint":false},{"year":2019,"finding":"Collecting duct-specific deletion of Cep164 in mice abolishes primary cilia from collecting duct epithelium and leads to rapid postnatal cyst growth driven by tubular hyperproliferation. Administration of the cell cycle inhibitor roscovitine blocked cyst growth, confirming cell cycle dysregulation as the primary cystogenesis mechanism.","method":"Conditional knockout mouse model (collecting duct-specific Cre), cell cycle analysis, biochemical studies, roscovitine pharmacological treatment","journal":"Kidney international","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO mouse with pharmacological rescue experiment; multiple methods confirming mechanism","pmids":["31248650"],"is_preprint":false},{"year":2020,"finding":"CEP164 co-localizes with GLI2 transcription factor at the mother centriole, controls GLI2 activation, and thereby regulates Cyclin D-CDK6 expression. Loss of CEP164 in pancreatic cancer cells enhances clonogenicity and alters cell cycle progression through cilia-independent GLI2-Cyclin D/CDK6 activation.","method":"CEP164 CRISPR/gene editing, immunofluorescence colocalization, cell cycle analysis, clonogenic assay, gene expression analysis","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO with colocalization and functional cell cycle readouts; single lab, multiple methods","pmids":["33251215"],"is_preprint":false},{"year":2021,"finding":"Structural and biochemical analysis reveals the molecular basis of the CEP164–TTBK2 complex and how it is disrupted by ciliopathic (nephronophthisis) CEP164 mutations. Binding to CEP164 is coordinated with TTBK2 kinase activities.","method":"Biochemical interaction assays, structural analysis (NMR/biophysical), mutagenesis of ciliopathic variants, functional ciliogenesis assays","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — structural and biochemical analysis with mutagenesis of disease variants; single lab but multiple orthogonal methods","pmids":["34499853"],"is_preprint":false},{"year":2021,"finding":"CEP164 recruits Chibby1 (Cby1) to basal bodies to facilitate basal body docking and multiciliogenesis in efferent ducts. FoxJ1-Cre;CEP164fl/fl mice show loss of multicilia in efferent ducts with accumulation of undocked basal bodies in the cytoplasm. The apical localization of Cby1 and the transition zone marker NPHP1 is severely diminished, indicating basal body docking defects.","method":"Conditional knockout mouse model, immunofluorescence, TEM, histology","journal":"Reproduction (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO mouse with TEM ultrastructural confirmation and multiple protein localization readouts; extends prior finding (PMID:29244804)","pmids":["34085951"],"is_preprint":false},{"year":2022,"finding":"Deletion of CEP164 post-ciliogenesis in rod photoreceptors impairs intraflagellar transport (IFT): IFT components IFT88, IFT57, and IFT140 were reduced at basal body and ciliary tip. CEP164 is also required for basal body docking to the apical membrane; retina-specific KO at embryonic stage prevents connecting cilium and outer segment formation. CEP164 is key for recruitment and stabilization of IFT-B particles at the basal body/connecting cilium.","method":"Conditional knockout mouse models (Six3Cre, iCre75, Prom1-ETCre tamoxifen-inducible), immunofluorescence, electron microscopy, fluorescent dye disc labeling","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple conditional KO models with temporal control, IFT component localization by IF, EM ultrastructure; single lab but comprehensive multi-model approach","pmids":["36074756"],"is_preprint":false},{"year":2023,"finding":"CEP164 physically interacts with GLI2 transcription factor at the mother centriole. The GLI2-binding region of CEP164, when ectopically expressed, reduces centriolar GLI2 localization and enhances expression of Hedgehog target genes, both in cells with and without primary cilia, demonstrating a cilia-independent role for CEP164 in controlling Hh signaling at the mother centriole.","method":"Co-immunoprecipitation, domain mapping, ectopic expression of CEP164 binding region, immunofluorescence colocalization, RT-PCR for Hh target genes","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping plus functional gene expression readout; single lab, multiple orthogonal methods","pmids":["37199136"],"is_preprint":false},{"year":2024,"finding":"Osteoblast-specific deletion of Cep164 in mice causes bone development defects and an increased number of γH2AX-positive cells in osteoblasts, indicating defective DNA damage response contributes to skeletal pathology. Chondrocyte-specific deletion causes no overt skeletal abnormalities, revealing cell-type-specific CEP164 function. Mesodermal cell-specific deletion results in severe bone defects.","method":"Conditional knockout mouse models (mesodermal-, osteoblast-, and chondrocyte-specific Cre), immunofluorescence for γH2AX, histology","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple tissue-specific KO models with phenotypic and molecular readouts; single lab","pmids":["39612644"],"is_preprint":false},{"year":2025,"finding":"CEP164 contains a long intrinsically disordered region and forms dynamic condensates with TTBK2 through liquid-liquid phase separation driven by multivalent electrostatic interactions. This phase separation facilitates efficient recruitment of TTBK2 to distal appendages to initiate ciliogenesis.","method":"Phase separation assays, electrostatic interaction analysis, live-cell imaging of condensates, TTBK2 recruitment assays, ciliogenesis rescue experiments","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro phase separation assays plus cell-based functional rescue; single lab, novel mechanism","pmids":["40483689"],"is_preprint":false},{"year":2025,"finding":"CEP164 homodimerizes via its central coiled-coil region, which is required for its mother centriole localization and subsequent TTBK2 recruitment. TTBK2 kinase activity plus its interaction with CEP164 are both required for recruitment of IFT-A, IFT-B, and dynein-2 complexes to, and removal of CP110 from, the mother centriole. CP110 removal is not always coupled with IFT protein recruitment.","method":"CEP164-KO and TTBK2-KO cell lines, chimeric/domain construct expression, co-immunoprecipitation, immunofluorescence for IFT and CP110","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO cell lines with chimeric domain rescue constructs and Co-IP; multiple orthogonal methods establishing homodimerization and IFT recruitment mechanism","pmids":["40305080"],"is_preprint":false},{"year":2025,"finding":"CEP164 at distal appendages is required for the enlargement of small vesicles docked to the mother centriole, a key trigger for ciliogenesis progression upstream of axoneme growth. These vesicles subsequently fuse to form tubular C-shaped and toroidal membrane intermediates that organize into the ciliary vesicle.","method":"Quantitative isotropic 3D ultrastructure imaging (focused ion beam SEM), protein localization, CEP164 loss-of-function","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — novel ultrastructural analysis with functional CEP164 requirement; preprint, single lab, not yet peer-reviewed","pmids":[],"is_preprint":true}],"current_model":"CEP164 is a distal appendage protein of the mother centriole that acts as a central scaffold for primary and multiciliogenesis: it recruits TTBK2 (via a proline-rich interaction, further stabilized by phase separation through multivalent electrostatic interactions) to trigger ciliogenesis by removing CP110 and recruiting IFT-A, IFT-B, and dynein-2 complexes; CEP164 homodimerizes via its coiled-coil domain to localize to the mother centriole; it facilitates basal body docking by recruiting Chibby1 and promoting ciliary vesicle enlargement and formation; it also controls ciliary targeting of membrane proteins (Rab8, Rab11, Arl13b) and anchors GLI2 at the mother centriole to regulate Hedgehog signaling independently of primary cilia; additionally, CEP164 functions in the ATR/ATM-mediated DNA damage response as a mediator phosphorylated at Ser186, though its requirement for DDR has been contested by genome-editing studies."},"narrative":{"mechanistic_narrative":"CEP164 is a distal appendage protein of the mother centriole that serves as a master scaffold for ciliogenesis [PMID:17954613]. It homodimerizes through its central coiled-coil region to achieve mother centriole localization, which is a prerequisite for its downstream recruiting functions [PMID:40305080]. CEP164's central activity is the recruitment of the kinase TTBK2 via a proline-rich interaction; this complex, whose structural basis and disruption by nephronophthisis-associated mutations have been defined, triggers ciliogenesis and is reinforced by liquid-liquid phase separation driven by multivalent electrostatic interactions through CEP164's intrinsically disordered region [PMID:24982133, PMID:25297623, PMID:34499853, PMID:40483689]. The CEP164-TTBK2 axis, dependent on TTBK2 kinase activity, drives removal of CP110 and recruitment of IFT-A, IFT-B, and dynein-2 complexes to the mother centriole [PMID:40305080], with CEP164 being required for stabilization of IFT-B at the basal body and connecting cilium in photoreceptors [PMID:36074756]. Beyond intraflagellar transport, CEP164 governs membrane events of ciliogenesis: it drives enlargement of small vesicles docked to the mother centriole into ciliary vesicle intermediates, recruits Chibby1 (and its partners FAM92A/FAM92B) to enable basal body docking, and controls ciliary targeting of membrane-associated proteins including Rab8, Rab11, Arl13b, and INPP5E [PMID:23150559, PMID:29244804, PMID:34085951]. CEP164 also anchors the GLI2 transcription factor at the mother centriole, restraining Hedgehog target-gene activation and Cyclin D-CDK6 expression in a cilia-independent manner [PMID:33251215, PMID:37199136]. Loss of CEP164 abolishes primary cilia and causes nephronophthisis-related ciliopathy phenotypes, including postnatal renal cyst growth driven by tubular hyperproliferation that is reversible by cell-cycle inhibition [PMID:22863007, PMID:31248650]. CEP164 was also characterized as an ATR/ATM-phosphorylated (Ser186) mediator of the DNA damage response [PMID:18283122], but rigorous genome-editing studies found no requirement for CEP164 in DDR signaling or nuclear localization [PMID:26966185].","teleology":[{"year":2007,"claim":"Established CEP164 as a distal appendage component of the mother centriole that is required for primary cilium formation, defining the structural platform on which all later mechanism rests.","evidence":"siRNA screen, immunogold electron microscopy, and RNAi knockdown with ciliogenesis readout in human cells","pmids":["17954613"],"confidence":"High","gaps":["Did not define molecular partners recruited by CEP164","Mechanism of distal appendage targeting unresolved"]},{"year":2008,"claim":"Addressed whether CEP164 has a nuclear function by identifying it as an ATR/ATM-phosphorylated (Ser186) mediator of the DNA damage response, implying a role beyond the centriole.","evidence":"Co-IP, in vitro kinase assay, phospho-specific antibodies, and checkpoint assays after replication stress/UV/IR","pmids":["18283122"],"confidence":"Medium","gaps":["Did not reconcile a centriolar protein acting in nuclear DDR","DDR requirement later contested by genome editing"]},{"year":2009,"claim":"Extended the proposed DDR role by showing UV-dependent CEP164 interaction with XPA and recruitment to lesion sites, linking CEP164 to nucleotide excision repair signaling.","evidence":"Co-IP, domain mapping, ChIP, CPD colocalization, and siRNA knockdown with survival/CHK1 readouts","pmids":["19197159"],"confidence":"Medium","gaps":["Single lab","Direct DDR requirement contradicted by later degron/CRISPR studies"]},{"year":2012,"claim":"Connected CEP164 loss to ciliopathy in vivo and to ciliary membrane-protein targeting, situating it within a discrete ARL13B-INPP5E-PDE6D network distinct from NPHP/MKS modules.","evidence":"DNA-damage foci colocalization, sensitivity assays, zebrafish morpholino, and pulldown/Co-IP with ciliary targeting analysis","pmids":["22863007","23150559"],"confidence":"Medium","gaps":["Direct vs. indirect interaction with INPP5E network not fully resolved","Mechanistic link between DDR and ciliopathy phenotype unclear"]},{"year":2014,"claim":"Defined the central ciliogenic mechanism: CEP164 recruits TTBK2 via a proline-rich motif to the mother centriole, an event required for CP110 removal and cilium initiation, with chimeric rescue proving sufficiency.","evidence":"Co-IP, domain mapping, binding-motif mutagenesis, chimeric protein rescue, and in vitro phosphorylation across two independent labs","pmids":["24982133","25297623"],"confidence":"High","gaps":["Did not resolve the structural basis of the interaction","Downstream IFT recruitment steps not yet mapped"]},{"year":2014,"claim":"Showed CEP164 depletion perturbs cell cycle progression and induces EMT/pro-fibrotic changes rescuable by wild-type but not disease-mutant CEP164, linking centriolar dysfunction to proliferative pathology.","evidence":"RPE-FUCCI live imaging, FACS, proliferation assays, RT-qPCR, zebrafish knockdown, and WT vs. mutant rescue","pmids":["25340510"],"confidence":"Medium","gaps":["Causal link between cilium loss and EMT not isolated","Single lab"]},{"year":2016,"claim":"Directly challenged the DDR model by showing that conditional degron depletion and CRISPR disruption of CEP164 block ciliogenesis without affecting irradiation sensitivity, and detected no nuclear CEP164.","evidence":"Auxin-inducible degron, genome editing, clonogenic survival assays, and multiple tagged CEP164 constructs in DT40 and RPE cells","pmids":["26966185"],"confidence":"Medium","gaps":["Cell-type-specific DDR contributions not excluded","Single lab negative result"]},{"year":2017,"claim":"Distinguished CEP164's roles in multiciliogenesis versus primary ciliogenesis, showing it controls vesicle recruitment, Chibby1 recruitment, basal body docking, and membrane-protein targeting but is dispensable for IFT recruitment in multicilia.","evidence":"FoxJ1-Cre conditional KO mouse, primary tracheal multiciliated cell cultures, immunofluorescence, and EM","pmids":["29244804"],"confidence":"High","gaps":["Molecular mechanism of vesicle recruitment not defined","Why IFT requirement differs between cilium types unexplained"]},{"year":2019,"claim":"Established the disease mechanism of renal cystogenesis: collecting-duct Cep164 deletion abolishes cilia and drives hyperproliferative cyst growth reversible by a cell-cycle inhibitor.","evidence":"Collecting duct-specific conditional KO mouse with roscovitine pharmacological rescue","pmids":["31248650"],"confidence":"High","gaps":["Signaling pathway linking cilium loss to hyperproliferation not fully mapped"]},{"year":2020,"claim":"Revealed a cilia-independent signaling role: CEP164 anchors GLI2 at the mother centriole to restrain Hedgehog-driven Cyclin D-CDK6 expression, with loss enhancing cancer cell clonogenicity.","evidence":"CRISPR KO, colocalization, cell cycle analysis, clonogenic assays, and gene expression in pancreatic cancer cells","pmids":["33251215"],"confidence":"Medium","gaps":["Single lab","Direct GLI2 binding not yet domain-mapped at this stage"]},{"year":2021,"claim":"Provided the structural basis of the CEP164-TTBK2 complex and showed how ciliopathic CEP164 mutations disrupt it, mechanistically connecting genotype to ciliogenesis failure.","evidence":"Structural/biophysical analysis, biochemical interaction assays, and mutagenesis of nephronophthisis variants with ciliogenesis readouts","pmids":["34499853"],"confidence":"High","gaps":["Full-length complex architecture in cellular context not resolved"]},{"year":2021,"claim":"Confirmed in efferent ducts that CEP164 recruits Chibby1 to mediate basal body docking, with loss causing undocked cytoplasmic basal bodies and diminished transition-zone marker localization.","evidence":"FoxJ1-Cre conditional KO mouse, immunofluorescence, TEM, and histology","pmids":["34085951"],"confidence":"High","gaps":["Direct biochemical CEP164-Chibby1 interaction not isolated here","Order of docking versus recruitment events unresolved"]},{"year":2022,"claim":"Demonstrated a post-ciliogenesis maintenance role: CEP164 is required for recruitment and stabilization of IFT-B particles and basal body docking in photoreceptors, with IFT88/57/140 reduced upon loss.","evidence":"Multiple conditional and inducible KO mouse models, immunofluorescence, EM, and disc labeling in rod photoreceptors","pmids":["36074756"],"confidence":"High","gaps":["Mechanism of IFT-B stabilization at the basal body not molecularly defined"]},{"year":2023,"claim":"Mapped the GLI2-binding region of CEP164 and showed its ectopic expression displaces centriolar GLI2 and de-represses Hedgehog targets in cells with or without cilia, confirming a cilia-independent signaling control point.","evidence":"Co-IP, domain mapping, ectopic binding-region expression, colocalization, and RT-PCR of Hh targets","pmids":["37199136"],"confidence":"Medium","gaps":["Single lab","How GLI2 anchoring is regulated physiologically unknown"]},{"year":2024,"claim":"Revealed cell-type-specific in vivo functions in skeleton, with osteoblast Cep164 loss increasing γH2AX-positive cells while chondrocyte deletion was benign, reopening a possible DDR-linked role in specific lineages.","evidence":"Mesodermal-, osteoblast-, and chondrocyte-specific conditional KO mice with γH2AX immunofluorescence and histology","pmids":["39612644"],"confidence":"Medium","gaps":["Whether γH2AX accumulation reflects a direct CEP164 DDR function is unresolved","Mechanism of cell-type specificity unknown"]},{"year":2025,"claim":"Integrated the recruiting mechanism: CEP164 homodimerizes via its coiled-coil for centriole localization, and forms phase-separated condensates with TTBK2 that, via TTBK2 kinase activity, drive CP110 removal and IFT-A/B and dynein-2 recruitment; vesicle enlargement was placed upstream of axoneme growth.","evidence":"KO cell lines with chimeric domain constructs, Co-IP, phase separation assays, live-cell condensate imaging, and FIB-SEM ultrastructure (one source a preprint)","pmids":["40305080","40483689"],"confidence":"High","gaps":["Physiological regulation of condensate formation not defined","Coupling between CP110 removal and IFT recruitment is variable and unexplained"]},{"year":null,"claim":"It remains unresolved whether CEP164 has any genuine, cell-type-restricted DNA damage response function, given the contradiction between early DDR mediator claims, the rigorous negative genome-editing study, and recent osteoblast γH2AX findings.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconciliation of nuclear DDR role with absence of detectable nuclear localization","Lineage-specific DDR contributions not mechanistically tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[5,6,9,18]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,18]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,5,11,15,18]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,9,14]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,5,9,18,19]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[11,15]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[3,10,12]}],"complexes":["centriole distal appendage"],"partners":["TTBK2","GLI2","CBY1","INPP5E","ARL13B","XPA","ATR","ATM"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UPV0","full_name":"Centrosomal protein of 164 kDa","aliases":[],"length_aa":1460,"mass_kda":164.3,"function":"Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9UPV0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP164","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000110274","cell_line_id":"CID000200","localizations":[{"compartment":"centrosome","grade":3}],"interactors":[{"gene":"RASGRP1","stoichiometry":0.2},{"gene":"GYS1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000200","total_profiled":1310},"omim":[{"mim_id":"615944","title":"C2 CALCIUM-DEPENDENT DOMAIN-CONTAINING PROTEIN 3; C2CD3","url":"https://www.omim.org/entry/615944"},{"mim_id":"615862","title":"NEPHRONOPHTHISIS 18; NPHP18","url":"https://www.omim.org/entry/615862"},{"mim_id":"615847","title":"CENTROSOMAL PROTEIN, 83-KD; CEP83","url":"https://www.omim.org/entry/615847"},{"mim_id":"615470","title":"CENTROSOMAL PROTEIN, 89-KD; CEP89","url":"https://www.omim.org/entry/615470"},{"mim_id":"614848","title":"CENTROSOMAL PROTEIN, 164-KD; CEP164","url":"https://www.omim.org/entry/614848"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Primary cilium transition zone","reliability":"Approved"},{"location":"Centrosome","reliability":"Approved"},{"location":"Principal piece","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Vesicles","reliability":"Additional"},{"location":"Equatorial segment","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP164"},"hgnc":{"alias_symbol":["KIAA1052","NPHP15"],"prev_symbol":[]},"alphafold":{"accession":"Q9UPV0","domains":[{"cath_id":"-","chopping":"7-105","consensus_level":"medium","plddt":85.8715,"start":7,"end":105},{"cath_id":"1.20.5","chopping":"629-805","consensus_level":"medium","plddt":91.8159,"start":629,"end":805},{"cath_id":"1.20.5","chopping":"833-972","consensus_level":"medium","plddt":93.3839,"start":833,"end":972}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UPV0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UPV0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UPV0-F1-predicted_aligned_error_v6.png","plddt_mean":61.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP164","jax_strain_url":"https://www.jax.org/strain/search?query=CEP164"},"sequence":{"accession":"Q9UPV0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UPV0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UPV0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UPV0"}},"corpus_meta":[{"pmid":"17954613","id":"PMC_17954613","title":"Cep164, a novel centriole appendage protein required for primary cilium formation.","date":"2007","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17954613","citation_count":427,"is_preprint":false},{"pmid":"22863007","id":"PMC_22863007","title":"Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22863007","citation_count":316,"is_preprint":false},{"pmid":"23150559","id":"PMC_23150559","title":"ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting.","date":"2012","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/23150559","citation_count":199,"is_preprint":false},{"pmid":"24982133","id":"PMC_24982133","title":"Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24982133","citation_count":156,"is_preprint":false},{"pmid":"18283122","id":"PMC_18283122","title":"Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1.","date":"2008","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/18283122","citation_count":79,"is_preprint":false},{"pmid":"25340510","id":"PMC_25340510","title":"Nephronophthisis-associated CEP164 regulates cell cycle progression, apoptosis and epithelial-to-mesenchymal transition.","date":"2014","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25340510","citation_count":63,"is_preprint":false},{"pmid":"25297623","id":"PMC_25297623","title":"Binding to Cep164, but not EB1, is essential for centriolar localization of TTBK2 and its function in ciliogenesis.","date":"2014","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/25297623","citation_count":55,"is_preprint":false},{"pmid":"29244804","id":"PMC_29244804","title":"Conditional knockout mice for the distal appendage protein CEP164 reveal its essential roles in airway multiciliated cell differentiation.","date":"2017","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29244804","citation_count":53,"is_preprint":false},{"pmid":"19197159","id":"PMC_19197159","title":"UV-dependent interaction between Cep164 and XPA mediates localization of Cep164 at sites of DNA damage and UV sensitivity.","date":"2009","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/19197159","citation_count":34,"is_preprint":false},{"pmid":"26966185","id":"PMC_26966185","title":"CEP164-null cells generated by genome editing show a ciliation defect with intact DNA repair capacity.","date":"2016","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26966185","citation_count":33,"is_preprint":false},{"pmid":"34085951","id":"PMC_34085951","title":"CEP164 is essential for efferent duct multiciliogenesis and male fertility.","date":"2021","source":"Reproduction (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/34085951","citation_count":25,"is_preprint":false},{"pmid":"36074756","id":"PMC_36074756","title":"Deletion of CEP164 in mouse photoreceptors post-ciliogenesis interrupts ciliary intraflagellar transport (IFT).","date":"2022","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36074756","citation_count":20,"is_preprint":false},{"pmid":"34499853","id":"PMC_34499853","title":"Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies.","date":"2021","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/34499853","citation_count":20,"is_preprint":false},{"pmid":"31248650","id":"PMC_31248650","title":"Roscovitine blocks collecting duct cyst growth in Cep164-deficient kidneys.","date":"2019","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/31248650","citation_count":15,"is_preprint":false},{"pmid":"33251215","id":"PMC_33251215","title":"CEP164 Deficiency Causes Hyperproliferation of Pancreatic Cancer Cells.","date":"2020","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/33251215","citation_count":13,"is_preprint":false},{"pmid":"31990917","id":"PMC_31990917","title":"Embryonic and foetal expression patterns of the ciliopathy gene CEP164.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/31990917","citation_count":8,"is_preprint":false},{"pmid":"36273371","id":"PMC_36273371","title":"Biallelic variants in CEP164 cause a motile ciliopathy-like syndrome.","date":"2022","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36273371","citation_count":7,"is_preprint":false},{"pmid":"37199136","id":"PMC_37199136","title":"CEP164-GLI2 association ensures the hedgehog signaling in pancreatic cancer cells.","date":"2023","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/37199136","citation_count":3,"is_preprint":false},{"pmid":"40483689","id":"PMC_40483689","title":"Phase separation of TTBK2 and CEP164 is necessary for ciliogenesis.","date":"2025","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/40483689","citation_count":2,"is_preprint":false},{"pmid":"39612644","id":"PMC_39612644","title":"Disruption of distal appendage protein CEP164 causes skeletal malformation in mice.","date":"2024","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/39612644","citation_count":1,"is_preprint":false},{"pmid":"40305080","id":"PMC_40305080","title":"Coordinated roles of the CEP164 homodimer and TTBK2 are required for recruitment of the IFT machinery to the mother centriole for ciliogenesis.","date":"2025","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/40305080","citation_count":1,"is_preprint":false},{"pmid":"41733187","id":"PMC_41733187","title":"Ameloblastoma Displays Primary Cilia Maintenance and CEP164 Overexpression.","date":"2026","source":"Journal of dental research","url":"https://pubmed.ncbi.nlm.nih.gov/41733187","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.20.670930","title":"Characterization of membrane structures regulating primary ciliogenesis by quantitative isotropic ultrastructure imaging","date":"2025-08-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.20.670930","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.10.648263","title":"A Role for Importin α in Ciliogenesis and Cilia Length Regulation during Nephrogenesis","date":"2025-04-14","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.10.648263","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12982,"output_tokens":5422,"usd":0.060138,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13917,"output_tokens":5118,"usd":0.098767,"stage2_stop_reason":"end_turn"},"total_usd":0.158905,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"CEP164 localizes to the distal appendages of mature centrioles (mother centriole), as determined by immunogold electron microscopy, and is indispensable for primary cilium formation. Unlike subdistal appendage proteins ninein and Cep170, CEP164 persists at centrioles throughout mitosis, and its localization is mutually independent of ninein/Cep170 during interphase.\",\n      \"method\": \"siRNA screen, immunogold electron microscopy, immunofluorescence, RNAi knockdown with ciliogenesis phenotype readout\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal localization studies with immunogold EM and functional RNAi knockdown; foundational paper replicated by multiple subsequent studies\",\n      \"pmids\": [\"17954613\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CEP164 (KIAA1052) interacts with both ATR and ATM kinases, is phosphorylated at Ser186 by ATR/ATM in vitro and in vivo upon replication stress, UV, and ionizing radiation, and functions as a mediator in the DNA damage response. MDC1 knockdown severely reduces Ser186 phosphorylation, and CEP164 knockdown diminishes DNA damage-induced phosphorylation of RPA, H2AX, MDC1, CHK2, and CHK1 (but not NBS1), and causes G2/M checkpoint defects.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, phospho-specific antibody analysis, cell cycle checkpoint assays\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro kinase assay plus Co-IP and functional knockdown; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"18283122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Upon UV irradiation, CEP164 interacts with XPA (Xeroderma pigmentosum group A) in a UV-dependent manner; CEP164 binds to amino acids 4–97 of XPA. XPA is required for recruitment of CEP164 to cyclobutane pyrimidine dimer (CPD) sites. CEP164 knockdown compromises cell survival upon UV damage and impairs UV-induced CHK1 phosphorylation.\",\n      \"method\": \"Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), immunofluorescence colocalization with CPD, siRNA knockdown, complementation with XPA deletion mutants\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and domain mapping plus functional knockdown and ChIP; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"19197159\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Upon induced DNA damage, CEP164 co-localizes to nuclear foci positive for TIP60 (an ATM activator) together with ZNF423 and NPHP10. CEP164 knockdown causes sensitivity to DNA damaging agents. Zebrafish cep164 knockdown results in dysregulated DDR and a nephronophthisis-related ciliopathy phenotype.\",\n      \"method\": \"Immunofluorescence colocalization at DNA damage foci, siRNA knockdown with DNA damage sensitivity assays, zebrafish morpholino knockdown\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (colocalization, sensitivity assays, in vivo model), single lab\",\n      \"pmids\": [\"22863007\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CEP164 physically interacts with INPP5E (inositol polyphosphate-5-phosphatase E) and participates in a functional network with ARL13B, INPP5E, and PDE6D for ciliary targeting of INPP5E. This network is distinct from those defined by NPHP and MKS proteins.\",\n      \"method\": \"Protein-protein interaction assays (pulldown/Co-IP), genetic analysis, ciliary targeting experiments\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP/pulldown interaction data combined with functional ciliary targeting analysis; single lab\",\n      \"pmids\": [\"23150559\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CEP164 recruits TTBK2 (Tau tubulin kinase 2) to the mother centriole to trigger ciliogenesis. CEP164 is a likely physiological substrate of TTBK2. Complex formation between CEP164 and TTBK2 is mediated by mapped interaction domains, and is essential for TTBK2 recruitment to basal bodies. Ciliogenesis can be rescued in CEP164-depleted cells by chimeric proteins fusing TTBK2 to the C-terminal centriole-targeting domain of CEP164. TTBK2 acts upstream of CEP164 to contribute to distal appendage assembly.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, siRNA knockdown, chimeric protein rescue, immunofluorescence\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, domain mapping, chimeric rescue experiments, and multiple functional readouts; replicated by independent lab (PMID:25297623)\",\n      \"pmids\": [\"24982133\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CEP164 is essential for TTBK2 centriolar localization via a proline-rich motif on TTBK2 (not via SxIP/EB1 motifs). TTBK2 non-Cep164-binding mutants fail to rescue CP110 removal and ciliogenesis in TTBK2-depleted cells. TTBK2 can phosphorylate CEP164 and Cep97, and TTBK2 kinase activity inhibits the CEP164–Dishevelled-3 interaction.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis of TTBK2 binding motifs, rescue experiments in TTBK2-depleted cells, in vitro phosphorylation assay\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — mutagenesis of binding domain plus functional rescue assays plus in vitro phosphorylation; independent replication of CEP164–TTBK2 complex (consistent with PMID:24982133)\",\n      \"pmids\": [\"25297623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CEP164 knockdown promotes cells to accumulate in S-phase and causes cell cycle acceleration, apoptosis, and epithelial-to-mesenchymal transition. These effects can be rescued by wild-type CEP164 but not disease-associated CEP164 mutants. Overexpression of dominant-negative CEP164 Q525X also induces EMT and pro-fibrotic gene upregulation.\",\n      \"method\": \"siRNA knockdown with live-cell imaging (RPE-FUCCI), FACS, CyQuant proliferation assay, immunofluorescence, RT-qPCR, zebrafish morpholino knockdown, rescue with WT vs. mutant CEP164\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (FACS, live imaging, in vivo model, mutant rescue); single lab\",\n      \"pmids\": [\"25340510\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NEGATIVE FINDING: Conditional depletion of CEP164 in DT40 cells (auxin-inducible degron) caused no increase in sensitivity to ionising or UV irradiation. Disruption of CEP164 in human RPE cells blocked primary cilium formation but did not affect proliferation or responses to ionising/UV irradiation. No nuclear localization of CEP164 was detected by immunofluorescence or analysis of multiple tagged forms of CEP164. These data suggest CEP164 is not required for the DNA damage response.\",\n      \"method\": \"Auxin-inducible degron conditional depletion, genome editing (CRISPR/reverse genetics), clonogenic survival assays, immunofluorescence with multiple tagged CEP164 constructs\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome editing plus multiple tagged constructs and functional assays; single lab but rigorous negative result contradicting earlier DDR claims\",\n      \"pmids\": [\"26966185\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CEP164 is required for multiciliogenesis via regulation of small vesicle recruitment, ciliary vesicle formation, and basal body docking. CEP164 is necessary for proper recruitment of Chibby1 (Cby1) and its binding partners FAM92A and FAM92B to the ciliary base in multiciliated cells. CEP164 controls ciliary targeting of membrane-associated proteins including Rab8, Rab11, and Arl13b. Unlike in primary ciliogenesis, CEP164 is dispensable for IFT component recruitment to multicilia.\",\n      \"method\": \"Conditional knockout mouse model (FoxJ1-Cre;CEP164fl/fl), primary tracheal multiciliated cell cultures, immunofluorescence, electron microscopy\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO mouse with multiple tissue readouts and primary cell cultures; multiple orthogonal methods (EM, IF, in vivo); single lab but rigorous and comprehensive\",\n      \"pmids\": [\"29244804\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Collecting duct-specific deletion of Cep164 in mice abolishes primary cilia from collecting duct epithelium and leads to rapid postnatal cyst growth driven by tubular hyperproliferation. Administration of the cell cycle inhibitor roscovitine blocked cyst growth, confirming cell cycle dysregulation as the primary cystogenesis mechanism.\",\n      \"method\": \"Conditional knockout mouse model (collecting duct-specific Cre), cell cycle analysis, biochemical studies, roscovitine pharmacological treatment\",\n      \"journal\": \"Kidney international\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO mouse with pharmacological rescue experiment; multiple methods confirming mechanism\",\n      \"pmids\": [\"31248650\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CEP164 co-localizes with GLI2 transcription factor at the mother centriole, controls GLI2 activation, and thereby regulates Cyclin D-CDK6 expression. Loss of CEP164 in pancreatic cancer cells enhances clonogenicity and alters cell cycle progression through cilia-independent GLI2-Cyclin D/CDK6 activation.\",\n      \"method\": \"CEP164 CRISPR/gene editing, immunofluorescence colocalization, cell cycle analysis, clonogenic assay, gene expression analysis\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO with colocalization and functional cell cycle readouts; single lab, multiple methods\",\n      \"pmids\": [\"33251215\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Structural and biochemical analysis reveals the molecular basis of the CEP164–TTBK2 complex and how it is disrupted by ciliopathic (nephronophthisis) CEP164 mutations. Binding to CEP164 is coordinated with TTBK2 kinase activities.\",\n      \"method\": \"Biochemical interaction assays, structural analysis (NMR/biophysical), mutagenesis of ciliopathic variants, functional ciliogenesis assays\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — structural and biochemical analysis with mutagenesis of disease variants; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"34499853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CEP164 recruits Chibby1 (Cby1) to basal bodies to facilitate basal body docking and multiciliogenesis in efferent ducts. FoxJ1-Cre;CEP164fl/fl mice show loss of multicilia in efferent ducts with accumulation of undocked basal bodies in the cytoplasm. The apical localization of Cby1 and the transition zone marker NPHP1 is severely diminished, indicating basal body docking defects.\",\n      \"method\": \"Conditional knockout mouse model, immunofluorescence, TEM, histology\",\n      \"journal\": \"Reproduction (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO mouse with TEM ultrastructural confirmation and multiple protein localization readouts; extends prior finding (PMID:29244804)\",\n      \"pmids\": [\"34085951\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Deletion of CEP164 post-ciliogenesis in rod photoreceptors impairs intraflagellar transport (IFT): IFT components IFT88, IFT57, and IFT140 were reduced at basal body and ciliary tip. CEP164 is also required for basal body docking to the apical membrane; retina-specific KO at embryonic stage prevents connecting cilium and outer segment formation. CEP164 is key for recruitment and stabilization of IFT-B particles at the basal body/connecting cilium.\",\n      \"method\": \"Conditional knockout mouse models (Six3Cre, iCre75, Prom1-ETCre tamoxifen-inducible), immunofluorescence, electron microscopy, fluorescent dye disc labeling\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple conditional KO models with temporal control, IFT component localization by IF, EM ultrastructure; single lab but comprehensive multi-model approach\",\n      \"pmids\": [\"36074756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CEP164 physically interacts with GLI2 transcription factor at the mother centriole. The GLI2-binding region of CEP164, when ectopically expressed, reduces centriolar GLI2 localization and enhances expression of Hedgehog target genes, both in cells with and without primary cilia, demonstrating a cilia-independent role for CEP164 in controlling Hh signaling at the mother centriole.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, ectopic expression of CEP164 binding region, immunofluorescence colocalization, RT-PCR for Hh target genes\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping plus functional gene expression readout; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"37199136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Osteoblast-specific deletion of Cep164 in mice causes bone development defects and an increased number of γH2AX-positive cells in osteoblasts, indicating defective DNA damage response contributes to skeletal pathology. Chondrocyte-specific deletion causes no overt skeletal abnormalities, revealing cell-type-specific CEP164 function. Mesodermal cell-specific deletion results in severe bone defects.\",\n      \"method\": \"Conditional knockout mouse models (mesodermal-, osteoblast-, and chondrocyte-specific Cre), immunofluorescence for γH2AX, histology\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple tissue-specific KO models with phenotypic and molecular readouts; single lab\",\n      \"pmids\": [\"39612644\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP164 contains a long intrinsically disordered region and forms dynamic condensates with TTBK2 through liquid-liquid phase separation driven by multivalent electrostatic interactions. This phase separation facilitates efficient recruitment of TTBK2 to distal appendages to initiate ciliogenesis.\",\n      \"method\": \"Phase separation assays, electrostatic interaction analysis, live-cell imaging of condensates, TTBK2 recruitment assays, ciliogenesis rescue experiments\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro phase separation assays plus cell-based functional rescue; single lab, novel mechanism\",\n      \"pmids\": [\"40483689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP164 homodimerizes via its central coiled-coil region, which is required for its mother centriole localization and subsequent TTBK2 recruitment. TTBK2 kinase activity plus its interaction with CEP164 are both required for recruitment of IFT-A, IFT-B, and dynein-2 complexes to, and removal of CP110 from, the mother centriole. CP110 removal is not always coupled with IFT protein recruitment.\",\n      \"method\": \"CEP164-KO and TTBK2-KO cell lines, chimeric/domain construct expression, co-immunoprecipitation, immunofluorescence for IFT and CP110\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO cell lines with chimeric domain rescue constructs and Co-IP; multiple orthogonal methods establishing homodimerization and IFT recruitment mechanism\",\n      \"pmids\": [\"40305080\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP164 at distal appendages is required for the enlargement of small vesicles docked to the mother centriole, a key trigger for ciliogenesis progression upstream of axoneme growth. These vesicles subsequently fuse to form tubular C-shaped and toroidal membrane intermediates that organize into the ciliary vesicle.\",\n      \"method\": \"Quantitative isotropic 3D ultrastructure imaging (focused ion beam SEM), protein localization, CEP164 loss-of-function\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — novel ultrastructural analysis with functional CEP164 requirement; preprint, single lab, not yet peer-reviewed\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CEP164 is a distal appendage protein of the mother centriole that acts as a central scaffold for primary and multiciliogenesis: it recruits TTBK2 (via a proline-rich interaction, further stabilized by phase separation through multivalent electrostatic interactions) to trigger ciliogenesis by removing CP110 and recruiting IFT-A, IFT-B, and dynein-2 complexes; CEP164 homodimerizes via its coiled-coil domain to localize to the mother centriole; it facilitates basal body docking by recruiting Chibby1 and promoting ciliary vesicle enlargement and formation; it also controls ciliary targeting of membrane proteins (Rab8, Rab11, Arl13b) and anchors GLI2 at the mother centriole to regulate Hedgehog signaling independently of primary cilia; additionally, CEP164 functions in the ATR/ATM-mediated DNA damage response as a mediator phosphorylated at Ser186, though its requirement for DDR has been contested by genome-editing studies.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP164 is a distal appendage protein of the mother centriole that serves as a master scaffold for ciliogenesis [#0]. It homodimerizes through its central coiled-coil region to achieve mother centriole localization, which is a prerequisite for its downstream recruiting functions [#18]. CEP164's central activity is the recruitment of the kinase TTBK2 via a proline-rich interaction; this complex, whose structural basis and disruption by nephronophthisis-associated mutations have been defined, triggers ciliogenesis and is reinforced by liquid-liquid phase separation driven by multivalent electrostatic interactions through CEP164's intrinsically disordered region [#5, #6, #12, #17]. The CEP164-TTBK2 axis, dependent on TTBK2 kinase activity, drives removal of CP110 and recruitment of IFT-A, IFT-B, and dynein-2 complexes to the mother centriole [#18], with CEP164 being required for stabilization of IFT-B at the basal body and connecting cilium in photoreceptors [#14]. Beyond intraflagellar transport, CEP164 governs membrane events of ciliogenesis: it drives enlargement of small vesicles docked to the mother centriole into ciliary vesicle intermediates, recruits Chibby1 (and its partners FAM92A/FAM92B) to enable basal body docking, and controls ciliary targeting of membrane-associated proteins including Rab8, Rab11, Arl13b, and INPP5E [#4, #9, #13, #19]. CEP164 also anchors the GLI2 transcription factor at the mother centriole, restraining Hedgehog target-gene activation and Cyclin D-CDK6 expression in a cilia-independent manner [#11, #15]. Loss of CEP164 abolishes primary cilia and causes nephronophthisis-related ciliopathy phenotypes, including postnatal renal cyst growth driven by tubular hyperproliferation that is reversible by cell-cycle inhibition [#3, #10]. CEP164 was also characterized as an ATR/ATM-phosphorylated (Ser186) mediator of the DNA damage response [#1], but rigorous genome-editing studies found no requirement for CEP164 in DDR signaling or nuclear localization [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established CEP164 as a distal appendage component of the mother centriole that is required for primary cilium formation, defining the structural platform on which all later mechanism rests.\",\n      \"evidence\": \"siRNA screen, immunogold electron microscopy, and RNAi knockdown with ciliogenesis readout in human cells\",\n      \"pmids\": [\"17954613\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define molecular partners recruited by CEP164\", \"Mechanism of distal appendage targeting unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Addressed whether CEP164 has a nuclear function by identifying it as an ATR/ATM-phosphorylated (Ser186) mediator of the DNA damage response, implying a role beyond the centriole.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, phospho-specific antibodies, and checkpoint assays after replication stress/UV/IR\",\n      \"pmids\": [\"18283122\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not reconcile a centriolar protein acting in nuclear DDR\", \"DDR requirement later contested by genome editing\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Extended the proposed DDR role by showing UV-dependent CEP164 interaction with XPA and recruitment to lesion sites, linking CEP164 to nucleotide excision repair signaling.\",\n      \"evidence\": \"Co-IP, domain mapping, ChIP, CPD colocalization, and siRNA knockdown with survival/CHK1 readouts\",\n      \"pmids\": [\"19197159\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct DDR requirement contradicted by later degron/CRISPR studies\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Connected CEP164 loss to ciliopathy in vivo and to ciliary membrane-protein targeting, situating it within a discrete ARL13B-INPP5E-PDE6D network distinct from NPHP/MKS modules.\",\n      \"evidence\": \"DNA-damage foci colocalization, sensitivity assays, zebrafish morpholino, and pulldown/Co-IP with ciliary targeting analysis\",\n      \"pmids\": [\"22863007\", \"23150559\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. indirect interaction with INPP5E network not fully resolved\", \"Mechanistic link between DDR and ciliopathy phenotype unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined the central ciliogenic mechanism: CEP164 recruits TTBK2 via a proline-rich motif to the mother centriole, an event required for CP110 removal and cilium initiation, with chimeric rescue proving sufficiency.\",\n      \"evidence\": \"Co-IP, domain mapping, binding-motif mutagenesis, chimeric protein rescue, and in vitro phosphorylation across two independent labs\",\n      \"pmids\": [\"24982133\", \"25297623\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the structural basis of the interaction\", \"Downstream IFT recruitment steps not yet mapped\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Showed CEP164 depletion perturbs cell cycle progression and induces EMT/pro-fibrotic changes rescuable by wild-type but not disease-mutant CEP164, linking centriolar dysfunction to proliferative pathology.\",\n      \"evidence\": \"RPE-FUCCI live imaging, FACS, proliferation assays, RT-qPCR, zebrafish knockdown, and WT vs. mutant rescue\",\n      \"pmids\": [\"25340510\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal link between cilium loss and EMT not isolated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Directly challenged the DDR model by showing that conditional degron depletion and CRISPR disruption of CEP164 block ciliogenesis without affecting irradiation sensitivity, and detected no nuclear CEP164.\",\n      \"evidence\": \"Auxin-inducible degron, genome editing, clonogenic survival assays, and multiple tagged CEP164 constructs in DT40 and RPE cells\",\n      \"pmids\": [\"26966185\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cell-type-specific DDR contributions not excluded\", \"Single lab negative result\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Distinguished CEP164's roles in multiciliogenesis versus primary ciliogenesis, showing it controls vesicle recruitment, Chibby1 recruitment, basal body docking, and membrane-protein targeting but is dispensable for IFT recruitment in multicilia.\",\n      \"evidence\": \"FoxJ1-Cre conditional KO mouse, primary tracheal multiciliated cell cultures, immunofluorescence, and EM\",\n      \"pmids\": [\"29244804\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism of vesicle recruitment not defined\", \"Why IFT requirement differs between cilium types unexplained\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Established the disease mechanism of renal cystogenesis: collecting-duct Cep164 deletion abolishes cilia and drives hyperproliferative cyst growth reversible by a cell-cycle inhibitor.\",\n      \"evidence\": \"Collecting duct-specific conditional KO mouse with roscovitine pharmacological rescue\",\n      \"pmids\": [\"31248650\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signaling pathway linking cilium loss to hyperproliferation not fully mapped\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Revealed a cilia-independent signaling role: CEP164 anchors GLI2 at the mother centriole to restrain Hedgehog-driven Cyclin D-CDK6 expression, with loss enhancing cancer cell clonogenicity.\",\n      \"evidence\": \"CRISPR KO, colocalization, cell cycle analysis, clonogenic assays, and gene expression in pancreatic cancer cells\",\n      \"pmids\": [\"33251215\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct GLI2 binding not yet domain-mapped at this stage\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Provided the structural basis of the CEP164-TTBK2 complex and showed how ciliopathic CEP164 mutations disrupt it, mechanistically connecting genotype to ciliogenesis failure.\",\n      \"evidence\": \"Structural/biophysical analysis, biochemical interaction assays, and mutagenesis of nephronophthisis variants with ciliogenesis readouts\",\n      \"pmids\": [\"34499853\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length complex architecture in cellular context not resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Confirmed in efferent ducts that CEP164 recruits Chibby1 to mediate basal body docking, with loss causing undocked cytoplasmic basal bodies and diminished transition-zone marker localization.\",\n      \"evidence\": \"FoxJ1-Cre conditional KO mouse, immunofluorescence, TEM, and histology\",\n      \"pmids\": [\"34085951\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical CEP164-Chibby1 interaction not isolated here\", \"Order of docking versus recruitment events unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated a post-ciliogenesis maintenance role: CEP164 is required for recruitment and stabilization of IFT-B particles and basal body docking in photoreceptors, with IFT88/57/140 reduced upon loss.\",\n      \"evidence\": \"Multiple conditional and inducible KO mouse models, immunofluorescence, EM, and disc labeling in rod photoreceptors\",\n      \"pmids\": [\"36074756\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of IFT-B stabilization at the basal body not molecularly defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapped the GLI2-binding region of CEP164 and showed its ectopic expression displaces centriolar GLI2 and de-represses Hedgehog targets in cells with or without cilia, confirming a cilia-independent signaling control point.\",\n      \"evidence\": \"Co-IP, domain mapping, ectopic binding-region expression, colocalization, and RT-PCR of Hh targets\",\n      \"pmids\": [\"37199136\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"How GLI2 anchoring is regulated physiologically unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed cell-type-specific in vivo functions in skeleton, with osteoblast Cep164 loss increasing γH2AX-positive cells while chondrocyte deletion was benign, reopening a possible DDR-linked role in specific lineages.\",\n      \"evidence\": \"Mesodermal-, osteoblast-, and chondrocyte-specific conditional KO mice with γH2AX immunofluorescence and histology\",\n      \"pmids\": [\"39612644\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether γH2AX accumulation reflects a direct CEP164 DDR function is unresolved\", \"Mechanism of cell-type specificity unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Integrated the recruiting mechanism: CEP164 homodimerizes via its coiled-coil for centriole localization, and forms phase-separated condensates with TTBK2 that, via TTBK2 kinase activity, drive CP110 removal and IFT-A/B and dynein-2 recruitment; vesicle enlargement was placed upstream of axoneme growth.\",\n      \"evidence\": \"KO cell lines with chimeric domain constructs, Co-IP, phase separation assays, live-cell condensate imaging, and FIB-SEM ultrastructure (one source a preprint)\",\n      \"pmids\": [\"40305080\", \"40483689\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological regulation of condensate formation not defined\", \"Coupling between CP110 removal and IFT recruitment is variable and unexplained\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved whether CEP164 has any genuine, cell-type-restricted DNA damage response function, given the contradiction between early DDR mediator claims, the rigorous negative genome-editing study, and recent osteoblast γH2AX findings.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconciliation of nuclear DDR role with absence of detectable nuclear localization\", \"Lineage-specific DDR contributions not mechanistically tested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [5, 6, 9, 18]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 18]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 5, 11, 15, 18]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 9, 14]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 5, 9, 18, 19]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [11, 15]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [3, 10, 12]}\n    ],\n    \"complexes\": [\"centriole distal appendage\"],\n    \"partners\": [\"TTBK2\", \"GLI2\", \"CBY1\", \"INPP5E\", \"ARL13B\", \"XPA\", \"ATR\", \"ATM\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}