{"gene":"CEP120","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2007,"finding":"CEP120 (Cep120) interacts with transforming acidic coiled-coil proteins (TACCs) and is required for interkinetic nuclear migration (INM) and neural progenitor self-renewal in the developing neocortex; silencing Cep120 impairs both INM and progenitor maintenance.","method":"shRNA-mediated silencing in developing neocortex, co-immunoprecipitation with TACC proteins","journal":"Neuron","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction plus in vivo loss-of-function with defined cellular phenotype, single lab","pmids":["17920017"],"is_preprint":false},{"year":2010,"finding":"Cep120 (Ccdc100) localizes preferentially and asymmetrically to the daughter centriole in cycling cells, with two kinetically distinct pools at the centriole (by FRAP); this asymmetry is relieved coincident with new centriole assembly. Cep120 is required for centriole duplication in cycling cells, centriole amplification in multiciliated cells, and centriole overduplication in S phase-arrested cells.","method":"Immunofluorescence, FRAP (photobleaching recovery analysis), siRNA depletion in cycling cells and MTECs, S-phase arrest assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (FRAP, immunolocalization, siRNA in multiple cell contexts) in a focused study","pmids":["20956381"],"is_preprint":false},{"year":2013,"finding":"CEP120 directly interacts with CPAP and is required for centriole elongation; CEP120 contains an N-terminal microtubule-binding domain, a C-terminal dimerization domain, and a centriolar localization domain. A microtubule binding-defective mutant (K76A) significantly suppresses elongated centriole formation. Forced overexpression of either CEP120 or CPAP induces overly long centrioles and supernumerary centrioles.","method":"Co-immunoprecipitation, domain mapping, mutagenesis (K76A), overexpression and depletion assays in human cells","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct interaction, domain mutagenesis, and reciprocal depletion assays all in one study","pmids":["23857771"],"is_preprint":false},{"year":2014,"finding":"Cep120 localizes to the daughter centriole via interaction with Talpid3 (Ta3); loss of Cep120 causes failed centriole duplication and consequent loss of ciliogenesis, abolishing Hedgehog pathway activity in cerebellar granule neuron progenitors (GNPs), leading to cerebellar hypoplasia. Cep120 null mice die in early gestation with abnormal heart looping.","method":"Conditional knockout mice, immunofluorescence, Co-IP (Cep120–Talpid3 interaction), Hedgehog signaling assays","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined cellular and signaling phenotypes, Co-IP interaction, replicated across multiple cell types","pmids":["25251415"],"is_preprint":false},{"year":2014,"finding":"A missense mutation in CEP120 (p.Ala199Pro) found in Jeune asphyxiating thoracic dystrophy (JATD) patients results in markedly reduced cilia number and abnormal centriole number in patient fibroblasts. Knockdown of the CEP120 ortholog in zebrafish produces cilia-defect phenotypes (body curvature, hydrocephalus, otolith defects, shortened neural tube cilia, disorganized pronephric cilia).","method":"Patient fibroblast analysis, zebrafish morpholino knockdown, cilia length/number quantification","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient cell analysis plus morpholino knockdown in zebrafish, single study","pmids":["25361962"],"is_preprint":false},{"year":2018,"finding":"CEP120 contains three C2 domains (C2A, C2B, C2C) followed by a coiled-coil dimerization domain. The N-terminal C2A domain binds tubulin and microtubules and promotes microtubule formation; a conserved positively charged patch on C2A mediates this interaction. Unlike classical C2 domains, all three Cep120 C2 domains lack calcium- and phospholipid-binding activity.","method":"X-ray crystallography, biophysical binding assays, mutagenesis of charged residues, in vitro microtubule polymerization assay","journal":"Journal of structural biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure, mutagenesis, and in vitro biochemical assays combined in one study","pmids":["29398280"],"is_preprint":false},{"year":2018,"finding":"CEP120 contains three C2 domains; ciliopathy-causing point mutations V194A (Joubert syndrome) and A199P (JATD) reduce thermostability of the second C2 domain by targeting residues pointing toward its hydrophobic core, leading to reduced CEP120 protein levels, compromised distal centriole marker recruitment, and deficient cilia formation.","method":"X-ray crystallography, thermal stability assays, genome engineering (CRISPR homozygous knock-in), immunofluorescence of centriole/cilia markers","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with genome-engineered disease mutant cell analysis and multiple orthogonal readouts","pmids":["29847808"],"is_preprint":false},{"year":2018,"finding":"In quiescent cells, Cep120 plays an inhibitory role at the daughter centriole, preventing premature pericentriolar material (PCM) accumulation (pericentrin, Cdk5Rap2, ninein, Cep170). Depletion of Cep120 causes increased PCM and elevated microtubule-nucleation activity, aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective cilia assembly and signaling.","method":"siRNA depletion in quiescent mouse and human cells, immunofluorescence, microtubule nucleation assay, centrosomal satellite localization","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal readouts (PCM accumulation, MT nucleation, satellite dispersal, ciliogenesis) in two cell species","pmids":["29741480"],"is_preprint":false},{"year":2019,"finding":"CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly (distal and subdistal appendages) and ciliogenesis. Loss of CEP120 causes short centrioles lacking appendages and impairs C2CD3 and Talpid3 recruitment to distal centriole ends. A disease-associated CEP120 mutant (I975S) has reduced affinity for C2CD3 and perturbs cilia assembly.","method":"CRISPR/Cas9 knockout in p53-deficient RPE1 cells, Co-IP, immunofluorescence, centriole appendage marker analysis, rescue with wild-type vs. I975S mutant","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO with multiple markers, Co-IP interactions, and disease mutant rescue experiments in one study","pmids":["30988386"],"is_preprint":false},{"year":2020,"finding":"A non-synonymous variant in CEP120 (p.Arg947His; rs2303720) causes decreased spindle microtubule nucleation efficiency and increased aneuploidy when expressed in mouse oocytes, implicating CEP120 in meiotic spindle assembly.","method":"Ectopic expression of CEP120 variant in mouse oocytes, spindle microtubule nucleation assay, chromosome segregation/aneuploidy assessment","journal":"Human reproduction (Oxford, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional oocyte assay with defined spindle phenotype, single lab, mouse model only","pmids":["32772081"],"is_preprint":false},{"year":2021,"finding":"CEP120 recruits KIAA0753 to centrioles, and loss of this interaction causes accumulation of granule neuron progenitors (GNPs) in the cerebellar germinal zone and impairs neuronal differentiation and cell cycle exit. JS-associated CEP120 mutants that hinder KIAA0753 recruitment fail to rescue these defects.","method":"Co-IP (CEP120–KIAA0753 interaction), shRNA depletion in vivo, immunofluorescence, rescue with WT vs. JS-mutant CEP120, in vivo cerebellar slice analysis","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP, in vivo loss-of-function, and mutant rescue with disease alleles in one study","pmids":["34711653"],"is_preprint":false},{"year":2023,"finding":"Conditional deletion of Cep120 in kidney stromal mesenchyme impairs centrosome duplication, causing delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, and altered Wnt and Hedgehog signaling, resulting in reduced stromal lineages, hypoplastic kidneys, and post-injury fibrosis via enhanced TGF-β/Smad3-Gli2 signaling.","method":"Conditional knockout mice, cell proliferation and apoptosis assays, signaling pathway analysis (Wnt, Hh, TGF-β/Smad3-Gli2), histology","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional genetic KO with multiple orthogonal phenotypic and signaling readouts in vivo","pmids":["38177914"],"is_preprint":false},{"year":2026,"finding":"A CEP120 knock-in mouse harboring the human variant (p.Arg947His) shows reduced female fertility and increased egg aneuploidy. Oocytes from variant mice have reduced microtubule nucleation efficiency after cold-induced depolymerization; in a pericentrin-depleted (humanized spindle) model, aneuploidy levels are significantly elevated in CEP120 variant eggs.","method":"Knock-in mouse model, microtubule regrowth assay after cold exposure, pericentrin depletion to model human spindle, aneuploidy quantification","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knock-in model with functional spindle and aneuploidy assays, single study, species difference caveat noted","pmids":["42096526"],"is_preprint":false}],"current_model":"CEP120 is a daughter centriole-enriched protein that promotes centriole elongation and duplication by binding tubulin/microtubules via its C2A domain and interacting with CPAP, C2CD3, Talpid3, and KIAA0753; it also plays an inhibitory role in quiescent cells to prevent premature PCM accumulation and daughter centriole maturation, recruits KIAA0753 to coordinate neuronal differentiation, and contributes to meiotic spindle microtubule nucleation, with ciliopathy-causing mutations destabilizing its C2 domain structure and impairing distal centriole appendage assembly and ciliogenesis."},"narrative":{"mechanistic_narrative":"CEP120 is a daughter-centriole-enriched protein that governs centriole biogenesis, elongation, and appendage assembly to support ciliogenesis and centriole-dependent signaling [PMID:20956381, PMID:23857771, PMID:30988386]. It binds tubulin and microtubules through a conserved positively charged patch on its N-terminal C2A domain and directly promotes microtubule formation; the protein is organized as three atypical C2 domains (which lack the calcium- and phospholipid-binding activity of classical C2 domains) followed by a coiled-coil dimerization domain [PMID:29398280]. Through direct interaction with CPAP, CEP120 drives centriole elongation, with microtubule-binding-defective and overexpression states perturbing centriole length and number [PMID:23857771]. CEP120 localizes to the daughter centriole via Talpid3 and cooperates with C2CD3 and Talpid3 to recruit distal-centriole factors and build distal and subdistal appendages required for cilium formation [PMID:25251415, PMID:30988386]. In quiescent cells it instead exerts an inhibitory role, restraining premature pericentriolar material accumulation, microtubule-nucleation activity, and centriolar satellite dispersal [PMID:29741480]. CEP120 also recruits KIAA0753 to centrioles to coordinate cerebellar granule neuron progenitor cell-cycle exit and differentiation, and supports meiotic spindle microtubule nucleation in oocytes [PMID:34711653, PMID:32772081]. Ciliopathy-causing mutations destabilize the second C2 domain or weaken partner binding, reducing CEP120 levels, impairing appendage and cilium assembly, and underlying Joubert syndrome and Jeune asphyxiating thoracic dystrophy [PMID:29847808, PMID:30988386]; in vivo loss of Cep120 disrupts Hedgehog and Wnt signaling and causes cerebellar hypoplasia and hypoplastic kidneys [PMID:25251415, PMID:38177914].","teleology":[{"year":2007,"claim":"Established CEP120 as a functionally important centrosomal protein in neural development by linking it to interkinetic nuclear migration and progenitor self-renewal, before its centriolar mechanism was known.","evidence":"shRNA silencing in developing neocortex with TACC Co-IP","pmids":["17920017"],"confidence":"Medium","gaps":["Did not define the molecular activity at the centriole","TACC interaction not mapped to a domain or validated reciprocally"]},{"year":2010,"claim":"Resolved where and when CEP120 acts by showing asymmetric daughter-centriole enrichment with two kinetic pools and a requirement for centriole duplication/amplification across cell contexts.","evidence":"Immunofluorescence, FRAP, and siRNA depletion in cycling cells, MTECs, and S-phase-arrested cells","pmids":["20956381"],"confidence":"High","gaps":["Molecular basis of daughter-centriole targeting unresolved","Did not identify direct binding partners driving duplication"]},{"year":2013,"claim":"Identified the elongation mechanism by showing CEP120 directly binds CPAP and that a microtubule-binding-defective mutant suppresses centriole elongation, defining its domain architecture.","evidence":"Co-IP, domain mapping, K76A mutagenesis, and overexpression/depletion in human cells","pmids":["23857771"],"confidence":"High","gaps":["Structural basis of microtubule binding not yet determined","How CPAP and CEP120 are coordinated temporally unclear"]},{"year":2014,"claim":"Connected CEP120 to ciliogenesis and Hedgehog-dependent development via Talpid3-mediated daughter-centriole localization and established its essentiality in vivo.","evidence":"Conditional knockout mice, Co-IP, and Hedgehog signaling assays in cerebellar progenitors","pmids":["25251415"],"confidence":"High","gaps":["Whether Talpid3 acts upstream or downstream in recruitment not fully separated","Heart-looping defect mechanism not dissected"]},{"year":2014,"claim":"Linked CEP120 to human ciliopathy by showing a JATD-associated missense variant reduces cilia and disrupts centriole number, with cross-species confirmation.","evidence":"Patient fibroblast analysis and zebrafish morpholino knockdown","pmids":["25361962"],"confidence":"Medium","gaps":["Molecular consequence of A199P not yet defined at this stage","Morpholino specificity limitations"]},{"year":2018,"claim":"Provided the structural and biochemical basis for CEP120 microtubule activity, revealing three atypical C2 domains and a C2A positively charged patch that binds tubulin and promotes microtubule formation.","evidence":"X-ray crystallography, biophysical binding assays, mutagenesis, and in vitro polymerization","pmids":["29398280"],"confidence":"High","gaps":["Roles of C2B and C2C domains not functionally assigned","In vitro activity not directly tied to centriole geometry in cells"]},{"year":2018,"claim":"Explained how ciliopathy point mutations cause disease by showing V194A and A199P destabilize the second C2 domain, lowering CEP120 levels and impairing distal-centriole recruitment and ciliogenesis.","evidence":"Crystallography, thermal stability assays, and CRISPR knock-in cells with marker imaging","pmids":["29847808"],"confidence":"High","gaps":["Whether protein destabilization fully accounts for phenotype versus loss of a specific interaction not separated"]},{"year":2018,"claim":"Revealed a context-dependent inhibitory function in quiescent cells, where CEP120 restrains PCM accumulation, microtubule nucleation, and satellite dispersal to permit proper ciliogenesis.","evidence":"siRNA depletion in quiescent mouse and human cells with PCM, nucleation, and satellite readouts","pmids":["29741480"],"confidence":"High","gaps":["Mechanism switching between elongation-promoting and inhibitory roles unclear","Direct PCM-restraining interactions not identified"]},{"year":2019,"claim":"Defined CEP120's role in appendage assembly by showing it interacts with C2CD3 and Talpid3 to recruit them to distal centriole ends and build appendages, with a disease mutant weakening C2CD3 binding.","evidence":"CRISPR knockout in RPE1 cells, Co-IP, appendage marker imaging, and WT vs. I975S rescue","pmids":["30988386"],"confidence":"High","gaps":["Order of recruitment among CEP120, C2CD3, and Talpid3 not fully resolved","Subdistal versus distal appendage contributions not separated"]},{"year":2020,"claim":"Extended CEP120 function to meiosis by showing a human variant reduces spindle microtubule nucleation and increases aneuploidy in oocytes.","evidence":"Ectopic expression of CEP120 R947H in mouse oocytes with nucleation and aneuploidy assays","pmids":["32772081"],"confidence":"Medium","gaps":["Ectopic expression rather than endogenous variant","Molecular mechanism of acentriolar spindle nucleation defect not defined"]},{"year":2021,"claim":"Identified KIAA0753 recruitment as the mechanism by which CEP120 controls cerebellar progenitor differentiation, with Joubert-syndrome mutants failing to rescue.","evidence":"Co-IP, in vivo shRNA depletion, and WT vs. JS-mutant rescue in cerebellar slices","pmids":["34711653"],"confidence":"High","gaps":["How KIAA0753 recruitment couples to cell-cycle exit signaling unclear"]},{"year":2023,"claim":"Demonstrated tissue-level consequences of CEP120 loss in kidney stroma, linking centrosome-duplication failure to mitotic surveillance-driven apoptosis and altered Wnt/Hh and TGF-β/Smad3-Gli2 signaling.","evidence":"Conditional knockout mice with proliferation, apoptosis, signaling, and histological analysis","pmids":["38177914"],"confidence":"High","gaps":["Direct molecular link between CEP120 and TGF-β/Smad3-Gli2 pathway not established","Cilia-dependent versus centriole-duplication contributions not fully separated"]},{"year":2026,"claim":"Validated the meiotic role of the human R947H variant in an endogenous knock-in model, showing reduced fertility, impaired microtubule regrowth, and elevated aneuploidy in a humanized-spindle context.","evidence":"Knock-in mouse, cold-induced microtubule regrowth assay, pericentrin depletion, and aneuploidy quantification","pmids":["42096526"],"confidence":"Medium","gaps":["Species difference in spindle architecture caveat","Mechanism by which the variant lowers nucleation efficiency not resolved"]},{"year":null,"claim":"How CEP120 switches between its elongation/duplication-promoting role and its quiescent-cell inhibitory role, and the functional division of labor among its three C2 domains, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No regulatory mechanism for the context-dependent switch identified","C2B and C2C domain functions unassigned","Recruitment hierarchy at distal centriole not fully ordered"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2,5]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,8,10]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1,2,7,8]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[3,4,8]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[5]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,2,8]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,9,11]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,3,10]}],"complexes":[],"partners":["CPAP","TALPID3","C2CD3","KIAA0753","TACC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N960","full_name":"Centrosomal protein of 120 kDa","aliases":["Coiled-coil domain-containing protein 100"],"length_aa":986,"mass_kda":112.6,"function":"Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis (By similarity). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q8N960/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP120","classification":"Not Classified","n_dependent_lines":44,"n_total_lines":1208,"dependency_fraction":0.03642384105960265},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CEP120","total_profiled":1310},"omim":[{"mim_id":"617761","title":"JOUBERT SYNDROME 31; JBTS31","url":"https://www.omim.org/entry/617761"},{"mim_id":"617728","title":"CENTROSOMAL PROTEIN, 295-KD; CEP295","url":"https://www.omim.org/entry/617728"},{"mim_id":"616300","title":"SHORT-RIB THORACIC DYSPLASIA 13 WITH OR WITHOUT POLYDACTYLY; SRTD13","url":"https://www.omim.org/entry/616300"},{"mim_id":"613447","title":"SPINDLE- AND CENTRIOLE-ASSOCIATED PROTEIN 1; SPICE1","url":"https://www.omim.org/entry/613447"},{"mim_id":"613446","title":"CENTROSOMAL PROTEIN, 120-KD; CEP120","url":"https://www.omim.org/entry/613446"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Microtubules","reliability":"Uncertain"},{"location":"Flagellar centriole","reliability":"Uncertain"},{"location":"Annulus","reliability":"Uncertain"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"},{"location":"Perinuclear theca","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP120"},"hgnc":{"alias_symbol":["FLJ36090"],"prev_symbol":["CCDC100"]},"alphafold":{"accession":"Q8N960","domains":[{"cath_id":"2.60.40.150","chopping":"8-135","consensus_level":"high","plddt":91.8444,"start":8,"end":135},{"cath_id":"2.60.40.150","chopping":"165-341","consensus_level":"high","plddt":87.7806,"start":165,"end":341},{"cath_id":"2.60.40.150","chopping":"453-608","consensus_level":"high","plddt":92.6085,"start":453,"end":608}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N960","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N960-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N960-F1-predicted_aligned_error_v6.png","plddt_mean":78.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP120","jax_strain_url":"https://www.jax.org/strain/search?query=CEP120"},"sequence":{"accession":"Q8N960","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N960.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N960/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N960"}},"corpus_meta":[{"pmid":"17920017","id":"PMC_17920017","title":"Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool.","date":"2007","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/17920017","citation_count":146,"is_preprint":false},{"pmid":"23857771","id":"PMC_23857771","title":"CEP120 interacts with CPAP and positively regulates centriole elongation.","date":"2013","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/23857771","citation_count":101,"is_preprint":false},{"pmid":"20956381","id":"PMC_20956381","title":"Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly.","date":"2010","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20956381","citation_count":100,"is_preprint":false},{"pmid":"25361962","id":"PMC_25361962","title":"A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies.","date":"2014","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25361962","citation_count":63,"is_preprint":false},{"pmid":"27208211","id":"PMC_27208211","title":"Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes.","date":"2016","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27208211","citation_count":52,"is_preprint":false},{"pmid":"25251415","id":"PMC_25251415","title":"Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25251415","citation_count":40,"is_preprint":false},{"pmid":"30988386","id":"PMC_30988386","title":"CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis.","date":"2019","source":"Scientific 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CC2D2A-With an emphasis on genotype-phenotype correlations, tissue specific transcripts and exploring mutation specific exon skipping therapies.","date":"2021","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33486889","citation_count":13,"is_preprint":false},{"pmid":"29398280","id":"PMC_29398280","title":"Cep120 promotes microtubule formation through a unique tubulin binding C2 domain.","date":"2018","source":"Journal of structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/29398280","citation_count":12,"is_preprint":false},{"pmid":"17920006","id":"PMC_17920006","title":"The ups and downs of neural progenitors: Cep120 and TACCs control interkinetic nuclear migration.","date":"2007","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/17920006","citation_count":11,"is_preprint":false},{"pmid":"34711653","id":"PMC_34711653","title":"CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum.","date":"2021","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/34711653","citation_count":7,"is_preprint":false},{"pmid":"38177914","id":"PMC_38177914","title":"Cep120 is essential for kidney stromal progenitor cell growth and differentiation.","date":"2023","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/38177914","citation_count":6,"is_preprint":false},{"pmid":"33297941","id":"PMC_33297941","title":"Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development.","date":"2020","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/33297941","citation_count":5,"is_preprint":false},{"pmid":"42096526","id":"PMC_42096526","title":"A human CEP120 gene variant impairs meiotic spindle building causing aneuploidy†.","date":"2026","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/42096526","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.12.03.24317221","title":"Assessing the diagnostic impact of blood transcriptome profiling in a pediatric cohort previously assessed by genome sequencing","date":"2024-12-05","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.03.24317221","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10126,"output_tokens":3342,"usd":0.040254,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10834,"output_tokens":4080,"usd":0.078085,"stage2_stop_reason":"end_turn"},"total_usd":0.118339,"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\": \"CEP120 (Cep120) interacts with transforming acidic coiled-coil proteins (TACCs) and is required for interkinetic nuclear migration (INM) and neural progenitor self-renewal in the developing neocortex; silencing Cep120 impairs both INM and progenitor maintenance.\",\n      \"method\": \"shRNA-mediated silencing in developing neocortex, co-immunoprecipitation with TACC proteins\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction plus in vivo loss-of-function with defined cellular phenotype, single lab\",\n      \"pmids\": [\"17920017\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Cep120 (Ccdc100) localizes preferentially and asymmetrically to the daughter centriole in cycling cells, with two kinetically distinct pools at the centriole (by FRAP); this asymmetry is relieved coincident with new centriole assembly. Cep120 is required for centriole duplication in cycling cells, centriole amplification in multiciliated cells, and centriole overduplication in S phase-arrested cells.\",\n      \"method\": \"Immunofluorescence, FRAP (photobleaching recovery analysis), siRNA depletion in cycling cells and MTECs, S-phase arrest assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (FRAP, immunolocalization, siRNA in multiple cell contexts) in a focused study\",\n      \"pmids\": [\"20956381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CEP120 directly interacts with CPAP and is required for centriole elongation; CEP120 contains an N-terminal microtubule-binding domain, a C-terminal dimerization domain, and a centriolar localization domain. A microtubule binding-defective mutant (K76A) significantly suppresses elongated centriole formation. Forced overexpression of either CEP120 or CPAP induces overly long centrioles and supernumerary centrioles.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, mutagenesis (K76A), overexpression and depletion assays in human cells\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct interaction, domain mutagenesis, and reciprocal depletion assays all in one study\",\n      \"pmids\": [\"23857771\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Cep120 localizes to the daughter centriole via interaction with Talpid3 (Ta3); loss of Cep120 causes failed centriole duplication and consequent loss of ciliogenesis, abolishing Hedgehog pathway activity in cerebellar granule neuron progenitors (GNPs), leading to cerebellar hypoplasia. Cep120 null mice die in early gestation with abnormal heart looping.\",\n      \"method\": \"Conditional knockout mice, immunofluorescence, Co-IP (Cep120–Talpid3 interaction), Hedgehog signaling assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined cellular and signaling phenotypes, Co-IP interaction, replicated across multiple cell types\",\n      \"pmids\": [\"25251415\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"A missense mutation in CEP120 (p.Ala199Pro) found in Jeune asphyxiating thoracic dystrophy (JATD) patients results in markedly reduced cilia number and abnormal centriole number in patient fibroblasts. Knockdown of the CEP120 ortholog in zebrafish produces cilia-defect phenotypes (body curvature, hydrocephalus, otolith defects, shortened neural tube cilia, disorganized pronephric cilia).\",\n      \"method\": \"Patient fibroblast analysis, zebrafish morpholino knockdown, cilia length/number quantification\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient cell analysis plus morpholino knockdown in zebrafish, single study\",\n      \"pmids\": [\"25361962\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CEP120 contains three C2 domains (C2A, C2B, C2C) followed by a coiled-coil dimerization domain. The N-terminal C2A domain binds tubulin and microtubules and promotes microtubule formation; a conserved positively charged patch on C2A mediates this interaction. Unlike classical C2 domains, all three Cep120 C2 domains lack calcium- and phospholipid-binding activity.\",\n      \"method\": \"X-ray crystallography, biophysical binding assays, mutagenesis of charged residues, in vitro microtubule polymerization assay\",\n      \"journal\": \"Journal of structural biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure, mutagenesis, and in vitro biochemical assays combined in one study\",\n      \"pmids\": [\"29398280\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CEP120 contains three C2 domains; ciliopathy-causing point mutations V194A (Joubert syndrome) and A199P (JATD) reduce thermostability of the second C2 domain by targeting residues pointing toward its hydrophobic core, leading to reduced CEP120 protein levels, compromised distal centriole marker recruitment, and deficient cilia formation.\",\n      \"method\": \"X-ray crystallography, thermal stability assays, genome engineering (CRISPR homozygous knock-in), immunofluorescence of centriole/cilia markers\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with genome-engineered disease mutant cell analysis and multiple orthogonal readouts\",\n      \"pmids\": [\"29847808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In quiescent cells, Cep120 plays an inhibitory role at the daughter centriole, preventing premature pericentriolar material (PCM) accumulation (pericentrin, Cdk5Rap2, ninein, Cep170). Depletion of Cep120 causes increased PCM and elevated microtubule-nucleation activity, aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective cilia assembly and signaling.\",\n      \"method\": \"siRNA depletion in quiescent mouse and human cells, immunofluorescence, microtubule nucleation assay, centrosomal satellite localization\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal readouts (PCM accumulation, MT nucleation, satellite dispersal, ciliogenesis) in two cell species\",\n      \"pmids\": [\"29741480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly (distal and subdistal appendages) and ciliogenesis. Loss of CEP120 causes short centrioles lacking appendages and impairs C2CD3 and Talpid3 recruitment to distal centriole ends. A disease-associated CEP120 mutant (I975S) has reduced affinity for C2CD3 and perturbs cilia assembly.\",\n      \"method\": \"CRISPR/Cas9 knockout in p53-deficient RPE1 cells, Co-IP, immunofluorescence, centriole appendage marker analysis, rescue with wild-type vs. I975S mutant\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO with multiple markers, Co-IP interactions, and disease mutant rescue experiments in one study\",\n      \"pmids\": [\"30988386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A non-synonymous variant in CEP120 (p.Arg947His; rs2303720) causes decreased spindle microtubule nucleation efficiency and increased aneuploidy when expressed in mouse oocytes, implicating CEP120 in meiotic spindle assembly.\",\n      \"method\": \"Ectopic expression of CEP120 variant in mouse oocytes, spindle microtubule nucleation assay, chromosome segregation/aneuploidy assessment\",\n      \"journal\": \"Human reproduction (Oxford, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional oocyte assay with defined spindle phenotype, single lab, mouse model only\",\n      \"pmids\": [\"32772081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CEP120 recruits KIAA0753 to centrioles, and loss of this interaction causes accumulation of granule neuron progenitors (GNPs) in the cerebellar germinal zone and impairs neuronal differentiation and cell cycle exit. JS-associated CEP120 mutants that hinder KIAA0753 recruitment fail to rescue these defects.\",\n      \"method\": \"Co-IP (CEP120–KIAA0753 interaction), shRNA depletion in vivo, immunofluorescence, rescue with WT vs. JS-mutant CEP120, in vivo cerebellar slice analysis\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP, in vivo loss-of-function, and mutant rescue with disease alleles in one study\",\n      \"pmids\": [\"34711653\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Conditional deletion of Cep120 in kidney stromal mesenchyme impairs centrosome duplication, causing delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, and altered Wnt and Hedgehog signaling, resulting in reduced stromal lineages, hypoplastic kidneys, and post-injury fibrosis via enhanced TGF-β/Smad3-Gli2 signaling.\",\n      \"method\": \"Conditional knockout mice, cell proliferation and apoptosis assays, signaling pathway analysis (Wnt, Hh, TGF-β/Smad3-Gli2), histology\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional genetic KO with multiple orthogonal phenotypic and signaling readouts in vivo\",\n      \"pmids\": [\"38177914\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"A CEP120 knock-in mouse harboring the human variant (p.Arg947His) shows reduced female fertility and increased egg aneuploidy. Oocytes from variant mice have reduced microtubule nucleation efficiency after cold-induced depolymerization; in a pericentrin-depleted (humanized spindle) model, aneuploidy levels are significantly elevated in CEP120 variant eggs.\",\n      \"method\": \"Knock-in mouse model, microtubule regrowth assay after cold exposure, pericentrin depletion to model human spindle, aneuploidy quantification\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knock-in model with functional spindle and aneuploidy assays, single study, species difference caveat noted\",\n      \"pmids\": [\"42096526\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP120 is a daughter centriole-enriched protein that promotes centriole elongation and duplication by binding tubulin/microtubules via its C2A domain and interacting with CPAP, C2CD3, Talpid3, and KIAA0753; it also plays an inhibitory role in quiescent cells to prevent premature PCM accumulation and daughter centriole maturation, recruits KIAA0753 to coordinate neuronal differentiation, and contributes to meiotic spindle microtubule nucleation, with ciliopathy-causing mutations destabilizing its C2 domain structure and impairing distal centriole appendage assembly and ciliogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP120 is a daughter-centriole-enriched protein that governs centriole biogenesis, elongation, and appendage assembly to support ciliogenesis and centriole-dependent signaling [#1, #2, #8]. It binds tubulin and microtubules through a conserved positively charged patch on its N-terminal C2A domain and directly promotes microtubule formation; the protein is organized as three atypical C2 domains (which lack the calcium- and phospholipid-binding activity of classical C2 domains) followed by a coiled-coil dimerization domain [#5]. Through direct interaction with CPAP, CEP120 drives centriole elongation, with microtubule-binding-defective and overexpression states perturbing centriole length and number [#2]. CEP120 localizes to the daughter centriole via Talpid3 and cooperates with C2CD3 and Talpid3 to recruit distal-centriole factors and build distal and subdistal appendages required for cilium formation [#3, #8]. In quiescent cells it instead exerts an inhibitory role, restraining premature pericentriolar material accumulation, microtubule-nucleation activity, and centriolar satellite dispersal [#7]. CEP120 also recruits KIAA0753 to centrioles to coordinate cerebellar granule neuron progenitor cell-cycle exit and differentiation, and supports meiotic spindle microtubule nucleation in oocytes [#10, #9]. Ciliopathy-causing mutations destabilize the second C2 domain or weaken partner binding, reducing CEP120 levels, impairing appendage and cilium assembly, and underlying Joubert syndrome and Jeune asphyxiating thoracic dystrophy [#6, #8]; in vivo loss of Cep120 disrupts Hedgehog and Wnt signaling and causes cerebellar hypoplasia and hypoplastic kidneys [#3, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established CEP120 as a functionally important centrosomal protein in neural development by linking it to interkinetic nuclear migration and progenitor self-renewal, before its centriolar mechanism was known.\",\n      \"evidence\": \"shRNA silencing in developing neocortex with TACC Co-IP\",\n      \"pmids\": [\"17920017\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define the molecular activity at the centriole\", \"TACC interaction not mapped to a domain or validated reciprocally\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Resolved where and when CEP120 acts by showing asymmetric daughter-centriole enrichment with two kinetic pools and a requirement for centriole duplication/amplification across cell contexts.\",\n      \"evidence\": \"Immunofluorescence, FRAP, and siRNA depletion in cycling cells, MTECs, and S-phase-arrested cells\",\n      \"pmids\": [\"20956381\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of daughter-centriole targeting unresolved\", \"Did not identify direct binding partners driving duplication\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified the elongation mechanism by showing CEP120 directly binds CPAP and that a microtubule-binding-defective mutant suppresses centriole elongation, defining its domain architecture.\",\n      \"evidence\": \"Co-IP, domain mapping, K76A mutagenesis, and overexpression/depletion in human cells\",\n      \"pmids\": [\"23857771\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of microtubule binding not yet determined\", \"How CPAP and CEP120 are coordinated temporally unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected CEP120 to ciliogenesis and Hedgehog-dependent development via Talpid3-mediated daughter-centriole localization and established its essentiality in vivo.\",\n      \"evidence\": \"Conditional knockout mice, Co-IP, and Hedgehog signaling assays in cerebellar progenitors\",\n      \"pmids\": [\"25251415\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Talpid3 acts upstream or downstream in recruitment not fully separated\", \"Heart-looping defect mechanism not dissected\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Linked CEP120 to human ciliopathy by showing a JATD-associated missense variant reduces cilia and disrupts centriole number, with cross-species confirmation.\",\n      \"evidence\": \"Patient fibroblast analysis and zebrafish morpholino knockdown\",\n      \"pmids\": [\"25361962\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular consequence of A199P not yet defined at this stage\", \"Morpholino specificity limitations\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided the structural and biochemical basis for CEP120 microtubule activity, revealing three atypical C2 domains and a C2A positively charged patch that binds tubulin and promotes microtubule formation.\",\n      \"evidence\": \"X-ray crystallography, biophysical binding assays, mutagenesis, and in vitro polymerization\",\n      \"pmids\": [\"29398280\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Roles of C2B and C2C domains not functionally assigned\", \"In vitro activity not directly tied to centriole geometry in cells\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Explained how ciliopathy point mutations cause disease by showing V194A and A199P destabilize the second C2 domain, lowering CEP120 levels and impairing distal-centriole recruitment and ciliogenesis.\",\n      \"evidence\": \"Crystallography, thermal stability assays, and CRISPR knock-in cells with marker imaging\",\n      \"pmids\": [\"29847808\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether protein destabilization fully accounts for phenotype versus loss of a specific interaction not separated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed a context-dependent inhibitory function in quiescent cells, where CEP120 restrains PCM accumulation, microtubule nucleation, and satellite dispersal to permit proper ciliogenesis.\",\n      \"evidence\": \"siRNA depletion in quiescent mouse and human cells with PCM, nucleation, and satellite readouts\",\n      \"pmids\": [\"29741480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism switching between elongation-promoting and inhibitory roles unclear\", \"Direct PCM-restraining interactions not identified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined CEP120's role in appendage assembly by showing it interacts with C2CD3 and Talpid3 to recruit them to distal centriole ends and build appendages, with a disease mutant weakening C2CD3 binding.\",\n      \"evidence\": \"CRISPR knockout in RPE1 cells, Co-IP, appendage marker imaging, and WT vs. I975S rescue\",\n      \"pmids\": [\"30988386\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Order of recruitment among CEP120, C2CD3, and Talpid3 not fully resolved\", \"Subdistal versus distal appendage contributions not separated\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended CEP120 function to meiosis by showing a human variant reduces spindle microtubule nucleation and increases aneuploidy in oocytes.\",\n      \"evidence\": \"Ectopic expression of CEP120 R947H in mouse oocytes with nucleation and aneuploidy assays\",\n      \"pmids\": [\"32772081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ectopic expression rather than endogenous variant\", \"Molecular mechanism of acentriolar spindle nucleation defect not defined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified KIAA0753 recruitment as the mechanism by which CEP120 controls cerebellar progenitor differentiation, with Joubert-syndrome mutants failing to rescue.\",\n      \"evidence\": \"Co-IP, in vivo shRNA depletion, and WT vs. JS-mutant rescue in cerebellar slices\",\n      \"pmids\": [\"34711653\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How KIAA0753 recruitment couples to cell-cycle exit signaling unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated tissue-level consequences of CEP120 loss in kidney stroma, linking centrosome-duplication failure to mitotic surveillance-driven apoptosis and altered Wnt/Hh and TGF-\\u03b2/Smad3-Gli2 signaling.\",\n      \"evidence\": \"Conditional knockout mice with proliferation, apoptosis, signaling, and histological analysis\",\n      \"pmids\": [\"38177914\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular link between CEP120 and TGF-\\u03b2/Smad3-Gli2 pathway not established\", \"Cilia-dependent versus centriole-duplication contributions not fully separated\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Validated the meiotic role of the human R947H variant in an endogenous knock-in model, showing reduced fertility, impaired microtubule regrowth, and elevated aneuploidy in a humanized-spindle context.\",\n      \"evidence\": \"Knock-in mouse, cold-induced microtubule regrowth assay, pericentrin depletion, and aneuploidy quantification\",\n      \"pmids\": [\"42096526\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Species difference in spindle architecture caveat\", \"Mechanism by which the variant lowers nucleation efficiency not resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP120 switches between its elongation/duplication-promoting role and its quiescent-cell inhibitory role, and the functional division of labor among its three C2 domains, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No regulatory mechanism for the context-dependent switch identified\", \"C2B and C2C domain functions unassigned\", \"Recruitment hierarchy at distal centriole not fully ordered\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 8, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1, 2, 7, 8]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [3, 4, 8]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 2, 8]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 9, 11]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 3, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CPAP\", \"Talpid3\", \"C2CD3\", \"KIAA0753\", \"TACC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}