Affinage

CEP290

Centrosomal protein of 290 kDa · UniProt O15078

Length
2479 aa
Mass
290.4 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP290 is a large multi-domain ciliary protein that functions as a structural tether and selective gatekeeper at the transition zone (TZ) connecting the ciliary membrane to axonemal microtubules, controlling protein entry and exit from the cilium (PMID:20819941, PMID:26982032). It directly binds membranes through an N-terminal amphipathic helix and microtubules through a domain in its myosin-tail homology region, with two autoinhibitory domains at the N and C termini regulating its activity; disruption of the microtubule-binding domain alone causes cilia deficits and retinal degeneration (PMID:24051377). In Chlamydomonas and vertebrate photoreceptors CEP290 forms the microtubule–membrane Y-linkers, localizing with nine-fold symmetry between the doublets and membrane along the connecting cilium (PMID:20819941, PMID:34520396). As a gating factor it prevents inappropriate entry of membrane-associated proteins and restrains leakage of ciliary proteins such as ARL13B through the TZ (PMID:26982032), and selectively controls trafficking of signaling cargoes including Hedgehog components (Smoothened, GPR161) and G proteins, with loss augmenting Hedgehog signaling (PMID:28700940, PMID:30478281, PMID:17898177). CEP290 also localizes to centriolar satellites in a PCM-1- and microtubule-dependent manner, where it organizes BBSome ciliary targeting and Rab8a delivery (PMID:18772192, PMID:18694559, PMID:22767577). It binds a network of ciliopathy proteins — NPHP5, CC2D2A, MKKS, RPGR, and the BBSome via BBS4 — to assemble and maintain TZ/satellite multiprotein complexes (PMID:18950740, PMID:23943788, PMID:18723859, PMID:22446187, PMID:26936822). CEP290 TZ localization is governed hierarchically by RPGRIP1L/MKS-5 and by cooperating basal-body modules (PMID:26982032, PMID:33625872, PMID:38442096), and the protein is specifically required for connecting cilium biogenesis, photoreceptor outer segment disc formation, and correct spatial distribution of TZ proteins AHI1 and NPHP1 (PMID:25859007, PMID:40704549). Mutations in CEP290 cause early-onset retinal degeneration, and both N-terminal and C-terminal fragments retain sufficient function to rescue ciliary and visual defects in vivo (PMID:16632484, PMID:21257638, PMID:30332642).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 Medium

    Established the basic subcellular distribution of CEP290 before its ciliary role was known, identifying a C-terminal determinant for nuclear/DNA-matrix association.

    Evidence Fluorescent fusion expression, subcellular fractionation, and truncation mapping in COS-7 cells

    PMID:15474516

    Open questions at the time
    • Functional consequence of nuclear localization not defined
    • Relationship between nuclear pool and ciliary pool unresolved
  2. 2006 High

    Linked CEP290 to photoreceptor ciliary transport in vivo, showing that an in-frame deletion causes retinal degeneration and redistribution of RPGR and phototransduction proteins.

    Evidence Genetic mapping, co-IP, and immunogold EM in rd16 mouse retina

    PMID:16632484

    Open questions at the time
    • Direct molecular basis of protein mislocalization not defined
    • Domain mediating RPGR association not mapped
  3. 2008 High

    Defined CEP290 as a centriolar satellite component and a hub of ciliopathy-protein interactions (PCM-1, CP110, CC2D2A, NPHP5) controlling ciliogenesis and Rab8a targeting.

    Evidence Co-IP, Y2H/GST pull-down, siRNA, and zebrafish/Xenopus epistasis across multiple studies

    PMID:18694559 PMID:18723859 PMID:18772192 PMID:18950740

    Open questions at the time
    • Order of complex assembly not resolved
    • Whether interactions are direct vs. complex-mediated varies by partner
  4. 2010 High

    Resolved CEP290's structural function, showing it forms the microtubule–membrane linkers tethering the flagellar membrane to TZ microtubules and influences ciliary protein composition.

    Evidence Immuno-EM, biochemical fractionation, and dikaryon rescue in Chlamydomonas cep290 deletion mutant

    PMID:20819941

    Open questions at the time
    • Molecular identity of the linker components beyond CEP290 unresolved
    • Direct vs. indirect contribution to IFT protein levels unclear
  5. 2011 Medium

    Demonstrated functional modularity, with the N-terminal region sufficient to restore vision and identifying RKIP as a partner whose accumulation impairs ciliogenesis via Rab8A.

    Evidence Zebrafish domain-rescue with human fragments and co-IP/immunofluorescence in rd16 retina

    PMID:21257638 PMID:21685394

    Open questions at the time
    • RKIP interaction confirmed in a single lab
    • How N-terminal sufficiency relates to full-length gating function unclear
  6. 2012 High

    Placed CEP290 within satellite trafficking hierarchies (Cep72-dependent recruitment) and defined direct partners (MKKS) whose disrupted association alters TZ complex integrity.

    Evidence Co-IP, siRNA hierarchy, in vitro interaction, and zebrafish/mouse compound-mutant epistasis

    PMID:22446187 PMID:22767577

    Open questions at the time
    • Paradoxical genetic rescue (rd16/Mkks) mechanism unresolved
    • Stoichiometry of TZ multiprotein complexes not defined
  7. 2013 High

    Mapped CEP290's biochemical activities — membrane and microtubule binding plus autoinhibition — and established interdependence with NPHP5 and BBSome (via BBS4) for ciliogenesis.

    Evidence Domain mapping, in vitro co-sedimentation, mutagenesis, mouse models, co-IP, and mouse epistasis

    PMID:23446637 PMID:23943788 PMID:24051377

    Open questions at the time
    • Structural basis of autoinhibition not solved
    • Trigger relieving autoinhibition in vivo unknown
  8. 2014 High

    Showed CEP290 acts through NPHP5 to maintain BBSome integrity and selective ciliary cargo delivery (Smoothened, VPAC2, Rab8a).

    Evidence Co-IP defining distinct BBS-binding sites, siRNA, and ciliary cargo trafficking assays

    PMID:25552655

    Open questions at the time
    • Mechanism by which CEP290 stabilizes BBSome subunit association unclear
    • Direct vs. indirect cargo selectivity not separated
  9. 2016 Medium

    Defined CEP290's role in the in vivo ciliary gate (preventing aberrant entry, retaining ARL-13) and revealed a nuclear/genome-stability function linked to replication and centriole number.

    Evidence C. elegans GFP gating assays and DNA fiber/γH2AX/CDK-rescue in primary kidney cells and zebrafish

    PMID:26301811 PMID:26982032

    Open questions at the time
    • Nuclear/DNA-damage function less independently replicated
    • Mechanistic link between ciliary and replication phenotypes unresolved
  10. 2017 Medium

    Established CEP290 as a selective gatekeeper for Hedgehog signaling cargo and identified additional satellite partners and an aggresome-seeding role.

    Evidence Patient fibroblasts/iPSC-optic cups with Hedgehog reporters, co-IP, and aggresome assembly assays

    PMID:28235840 PMID:28700940 PMID:35411088

    Open questions at the time
    • Direct CCDC66 binding interface not mapped
    • Generality of aggresome role beyond tested cargoes unknown
  11. 2018 Medium

    Connected a specific CEP290 missense variant to a defective ciliary diffusion barrier and Hedgehog/RPGR-dependent disease modification, and demonstrated C-terminal domain sufficiency for therapeutic rescue.

    Evidence FRAP and Shh assays in patient iPSC, RPGR co-IP/mouse epistasis, and AAV C-terminal complementation in rd16 mice and organoids

    PMID:26936822 PMID:30332642 PMID:30478281

    Open questions at the time
    • Allele-specific (rd16) nature of RPGR modification limits generalization
    • How a single missense disrupts the barrier mechanistically unresolved
  12. 2021 Medium

    Provided sub-diffraction structural localization across cell types and defined upstream regulators (RPGRIP1L) and compensatory GTPase trafficking pathways.

    Evidence STORM/STED and EM in mouse photoreceptors and RPE-1, mouse Rpgrip1l genetics, and zebrafish RNA-seq/rescue with arl3/arl13b/unc119b

    PMID:33625872 PMID:34155518 PMID:34520396

    Open questions at the time
    • Why Y-links persist in CEP290-deficient photoreceptors unresolved
    • Mechanism of eupatilin/compensatory rescue unknown
  13. 2024 High

    Mapped the cooperative basal-body module network that recruits CEP290 to initiate ciliogenesis.

    Evidence Drosophila single and double deletion genetics with ciliogenesis-initiation assays

    PMID:38442096

    Open questions at the time
    • Biochemical nature of module-CEP290 contacts not defined
    • Conservation of the dual-module logic in vertebrates untested here
  14. 2025 High

    Defined CEP290's role in spatial organization of the connecting cilium, showing selective confinement of AHI1/NPHP1 and failure of outer segment disc formation upon loss.

    Evidence EM and selective protein localization in Cep290 conditional KO mouse photoreceptors during development

    PMID:40704549

    Open questions at the time
    • Mechanism restricting AHI1/NPHP1 distribution unresolved
    • Origin of accumulating extracellular vesicles unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEP290's autoinhibition is relieved and how it achieves cargo-selective gating at the molecular level remains unresolved.
  • No high-resolution structure of CEP290 or its TZ linker assembly
  • Mechanism distinguishing permitted vs. blocked cargo undefined
  • Functional significance of nuclear CEP290 pool unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0003677 DNA binding 1 GO:0008289 lipid binding 1
Localization
GO:0005929 cilium 4 GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2
Partners
BBS4CC2D2ACP110MKKSNPHP5PCM1RPGRRPGRIP1L
Complex memberships
CP110-CEP97-CEP290 complexcentriolar satellitesciliary transition zone (MKS module)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CEP290 localizes to centrosomes of dividing cells and to the connecting cilium of retinal photoreceptors. In the rd16 mouse, an in-frame deletion in CEP290 causes early-onset retinal degeneration; the truncated CEP290 protein (ΔCep290) shows stronger association with specific RPGR isoform(s), and RPGR and phototransduction proteins are redistributed in rd16 photoreceptors, implicating CEP290 in ciliary transport and polarized protein distribution in photoreceptors. Genetic mapping, immunolocalization, co-immunoprecipitation, immunogold electron microscopy in rd16 mouse retina Human molecular genetics High 16632484
2010 In Chlamydomonas, CEP290 is located in the flagellar transition zone and forms microtubule-membrane linkers that tether the flagellar membrane to transition zone microtubules; loss of CEP290 causes defects in these connectors and abnormal flagellar protein composition including altered levels of IFT proteins. CEP290 at the transition zone undergoes rapid turnover as shown by dikaryon experiments. Immunoelectron microscopy, ultrastructural analysis, biochemical fractionation of isolated flagella, dikaryon rescue experiments in Chlamydomonas cep290 deletion mutant The Journal of cell biology High 20819941
2008 CEP290 interacts with the centriolar satellite protein PCM-1; CEP290 localizes to centriolar satellites in a PCM-1- and microtubule-dependent manner. Depletion of CEP290 disrupts PCM-1 distribution and complex formation, disorganizes the cytoplasmic microtubule network, impairs ciliogenesis, and prevents ciliary targeting of Rab8a. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, microtubule disruption assays in cultured cells Human molecular genetics High 18772192
2008 CP110 interacts with CEP290 in a discrete complex separable from other CP110 complexes. Interaction with CEP290 is required for CP110 to suppress primary cilia formation. Both CEP290 and CP110 interact with Rab8a; depletion of CEP290 prevents ciliogenesis and interferes with Rab8a localization to centrosomes and cilia. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliogenesis assays Developmental cell High 18694559
2007 CEP290/NPHP6 is required for G protein (Golf and Gγ13) trafficking into olfactory sensory neuron cilia; in rd16 hypomorphic CEP290 mice, olfactory cilia remain intact but Golf and Gγ13 fail to localize to cilia while G protein-coupled odorant receptors and other odorant signaling pathway components are unaffected. CEP290 localizes to dendritic knobs of OSNs in complex with ciliary transport proteins and olfactory G proteins. Electro-olfactogram recordings, immunofluorescence, co-immunoprecipitation in rd16 mouse olfactory tissue Proceedings of the National Academy of Sciences of the United States of America High 17898177
2008 CC2D2A physically interacts with CEP290 at the basal body (shown by yeast two-hybrid and GST pull-down), co-localizes with CEP290 in ciliated cells, and genetically interacts with CEP290 in zebrafish: combined subminimal knockdown of CC2D2A and cep290 produces synergistic pronephric cyst phenotype. Yeast two-hybrid, GST pull-down, immunofluorescence co-localization, zebrafish morpholino epistasis American journal of human genetics High 18950740
2012 CEP290 localizes to the transition zone at the Y-linker region between central microtubules and plasma membrane in photoreceptor connecting cilia and other ciliated cells. Complete knockout (Cep290ko/ko) mice lack connecting cilia in retinal photoreceptors and fail to mature ciliated ventricular ependyma, demonstrating CEP290 is required for connecting cilia biogenesis. Immunofluorescence, electron microscopy, genetic KO mouse models (Cep290ko/ko and Cep290gt/gt) Human molecular genetics High 25859007
2013 CEP290 directly binds cellular membranes through an N-terminal amphipathic helix domain and to microtubules through a domain within its myosin-tail homology region. CEP290 activity is regulated by two autoinhibitory domains at the N and C termini. Disruption of the microtubule-binding domain in a mouse model is sufficient to cause cilia formation deficits and retinal degeneration. Domain mapping, in vitro binding assays (membrane and microtubule co-sedimentation), mutagenesis, in vivo mouse model analysis The Journal of clinical investigation High 24051377
2013 BBSome physically interacts with CEP290 via BBS4 binding to the N-terminal region of CEP290. BBSome co-localizes with CEP290 at the transition zone, centriolar satellites, and connecting cilium. In BBSome-depleted cells, CEP290 still localizes to TZ and connecting cilium but its centriolar satellite localization is disrupted. Genetic interaction: additional loss of Bbs4 alleles in Cep290rd16 mice accelerates photoreceptor degeneration and increases body weight. Co-immunoprecipitation, immunofluorescence, siRNA depletion, Cep290rd16/Bbs4-null double-mutant mouse epistasis Human molecular genetics High 23943788
2012 Cep290 and Cep72 interact with PCM-1 at centriolar satellites. Cep72 is required for recruitment of Cep290 to centriolar satellites. Loss of PCM-1 satellites relocalizes Cep72 and Cep290 to the centrosome. Depletion of Cep290 or Cep72, but not loss of centriolar satellites, impairs ciliary recruitment of the BBSome subunit BBS8 during ciliogenesis, defining a Cep72-Cep290 pathway for BBSome ciliary targeting. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, zebrafish morpholino knockdown Molecular biology of the cell High 22767577
2008 The N-terminal domain of nephrocystin-6 (CEP290/NPHP6) directly binds nephrocystin-5 (NPHP5); the interacting region maps to amino acids 696-896 of NPHP6. Combined knockdown of zNPHP5 and zNPHP6 in zebrafish produces synergistic phenotypes. Expression of the NPHP5-binding fragment of NPHP6 in Xenopus phenocopies NPHP5 knockdown neural tube closure defects, which are rescued by co-expression of NPHP5. Pull-down interaction mapping, zebrafish morpholino co-knockdown epistasis, Xenopus overexpression/rescue experiments Human molecular genetics High 18723859
2012 The domain deleted in the Cep290rd16 mutant protein directly interacts with the ciliopathy protein MKKS; BBS mutations in patients disrupt this interaction. Combined subminimal knockdown of mkks and cep290 in zebrafish causes sensory defects. Paradoxically, combinations of Cep290rd16 and Mkksko alleles in mice improve ciliogenesis and sensory functions compared to either single mutant, suggesting that altered Cep290-MKKS association affects multiprotein complex integrity at the transition zone/basal body. In vitro interaction assay, zebrafish morpholino epistasis, Cep290rd16/Mkksko compound mouse mutant analysis, ciliogenesis assays The Journal of clinical investigation High 22446187
2014 NPHP5 contains two separate BBS-binding sites and interacts with the BBSome to mediate its integrity. Depletion of Cep290, which directly binds NPHP5, causes additional dissociation of BBS8 from the BBSome and loss of ciliary BBS8 beyond the BBS2/BBS5 loss seen with NPHP5 depletion alone. Delivery of BBSome cargos (smoothened, VPAC2, Rab8a) to cilia is selectively impaired in the absence of NPHP5 or Cep290. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliary cargo trafficking assays Human molecular genetics High 25552655
2013 NPHP5 interaction with Cep290 is required for NPHP5 function in ciliogenesis: disease-causing NPHP5 truncation mutations cannot bind Cep290 and fail to localize to centrosomes, thereby preventing cilia formation. Drugs antagonizing negative regulators of ciliogenesis rescue cilia in NPHP5-depleted cells with response profiles matching Cep290-depleted cells, further linking the two proteins to a common ciliogenic pathway. Co-immunoprecipitation, mutagenesis of patient alleles, immunofluorescence, pharmacological rescue Human molecular genetics High 23446637
2016 In C. elegans, CEP-290 (Cep290 ortholog) is a central MKS module assembly factor that depends on the coiled-coil region of MKS-5 (Rpgrip1L) for TZ localization. CEP-290 prevents inappropriate membrane-associated protein entry into cilia and keeps ARL-13 from leaking out through the TZ gate, defining CEP290 as essential for ciliary gating function. Multiple TZ proteins including TMEM-138 and CDKL-1 require CEP-290 for TZ localization. C. elegans genetics, GFP reporter ciliary entry/exit assays, epistasis of module localization hierarchy PLoS biology High 26982032
2020 In Drosophila, the N-terminus of CEP290 directly recruits DZIP1 to the transition zone; DZIP1 then recruits Chibby (CBY) and Rab8 to promote early ciliary membrane formation. Complete CEP290 deletion blocks ciliogenesis at the TZ assembly initiation stage, which is phenocopied by DZIP1 mutants lacking the CEP290-binding domain. Expression of the CEP290 N-terminus alone is sufficient to restore DZIP1 TZ localization and ameliorate TZ assembly defects. Drosophila genetics, in vitro pull-down, immunofluorescence, domain rescue experiments PLoS biology High 33370260
2015 CEP290 loss results in enhanced DNA damage signaling and accumulation of DNA breaks in primary kidney cells and zebrafish embryos. Cep290-deficient cells exhibit supernumerary centrioles, decreased replication fork velocity, fork asymmetry, and increased CDK levels. CDK inhibition rescues both DNA damage and centriole number in Cep290-deficient cells and restores primary cilia loss in 3D kidney cell spheroids. DNA fiber assay (replication fork analysis), γH2AX immunofluorescence, centriole counting, CDK inhibitor rescue, primary murine kidney cells and zebrafish morpholino The Journal of clinical investigation Medium 26301811
2004 CEP290 (3H11Ag) localizes to both cytoplasm and nucleus; nuclear CEP290 associates with DNA and the nuclear matrix. The C-terminal 150 amino acid residues are responsible for this subcellular localization. Fluorescent protein fusion expression in COS-7 cells, subcellular fractionation, sequential nuclear extraction, truncation mapping Biochemical and biophysical research communications Medium 15474516
2011 CEP290-mediated photoreceptor degeneration is associated with aberrant accumulation of the novel CEP290 interacting partner RKIP (Raf-1 kinase inhibitory protein) in rd16 retina. Ectopic RKIP accumulation causes defective cilia formation, an effect mediated by RKIP interaction with the ciliary GTPase Rab8A. This phenotype is reproduced by cep290 morpholino knockdown in zebrafish. Co-immunoprecipitation (CEP290-RKIP interaction), immunofluorescence in rd16 mouse retina, zebrafish morpholino knockdown, ciliogenesis assays The Journal of biological chemistry Medium 21685394
2016 Physical interaction between RPGR and the C-terminal domain of CEP290 was demonstrated. Genetically, Rpgrko/Y mice with a heterozygous hypomorphic Cep290rd16 allele (but not a null or other ciliopathy gene heterozygotes) develop early-onset retinal degeneration with disorganized outer segments and defective opsin trafficking, establishing Cep290 as a modifier of RPGR-associated retinal degeneration. Co-immunoprecipitation (RPGR–CEP290 C-terminal domain), mouse genetic epistasis (Rpgrko/Cep290rd16 compound mutants), immunofluorescence Human molecular genetics Medium 26936822
2013 SSX2IP localizes to the basal body and is required for efficient recruitment of Cep290 to centriolar satellites and the basal body. Loss of SSX2IP reduces BBSome ciliary entry and Rab8 accumulation at cilia, and decreases ciliary targeting of the membrane protein somatostatin receptor 3, placing SSX2IP upstream of Cep290 in satellite-mediated ciliary trafficking. siRNA knockdown, immunofluorescence, ciliary trafficking assays for membrane cargo Molecular biology of the cell Medium 24356449
2017 In JSRD fibroblasts lacking CEP290, ciliogenesis is abnormal and localization of ADCY3 and ARL13B in cilia is selectively reduced. Hedgehog signaling is augmented in CEP290-JSRD cells due to enhanced ciliary transport of Smoothened and GPR161, establishing CEP290 as a selective gatekeeper for transport of Hedgehog signaling molecules. Patient-derived fibroblasts and iPSC-optic cups, immunofluorescence, Hedgehog pathway reporter assays Cell reports Medium 28700940
2021 RPGRIP1L governs ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone; loss of Rpgrip1l reduces Cep290 at the TZ and impairs gating. The flavonoid eupatilin rescues ciliary gating defects caused by Rpgrip1l loss. Mouse genetics (Rpgrip1l mutants), immunofluorescence quantification of Cep290 at TZ, ciliary gating reporter assays, pharmacological rescue Molecular biology of the cell Medium 33625872
2022 CP110, CEP97, and CEP290 together seed the initial phosphorylated HSP27 ring at the centrosome required for aggresome assembly. Centriolar satellites are required for subsequent aggresome growth from this ring. CP110-CEP97-CEP290 are also required for aggregation of mutant huntingtin protein. siRNA/CRISPR knockdown, high-resolution microscopy (aggresome assembly assays), phospho-HSP27 immunofluorescence Nature cell biology Medium 35411088
2018 A CEP290 missense variant (R1747Q/R1746Q) disrupts the ciliary diffusion barrier, causes mislocalization of the Hedgehog receptor Smoothened, and impairs Sonic Hedgehog signaling response in cerebellar granule progenitors, leading to proliferation defects. This was confirmed in an autism patient-derived iPSC line. FRAP (ciliary protein mobility), immunofluorescence (Smo localization), Shh signaling assay, patient iPSC-derived cells Scientific reports Medium 30478281
2017 CCDC66 is a centriolar satellite protein that co-immunoprecipitates with both CEP290 and PCM1. Depletion of CCDC66 impairs ciliogenesis, ciliary BBS4 recruitment, and centriolar satellite organization. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliogenesis assays Journal of cell science Medium 28235840
2021 Super-resolution microscopy localizes CEP290 radially between the microtubule doublets and the ciliary membrane throughout the full length of the connecting cilium in photoreceptors, with nine-fold symmetry. In contrast, in RPE-1 cells CEP290 is confined to the very base of primary cilia. Severe CEP290 deficiency does not prevent earliest cilia assembly but results in fewer cilia, no normal outer segments, and abnormal connecting cilium membrane; Y-shaped links are still present in CEP290-deficient photoreceptors. Super-resolution fluorescence microscopy (STORM/STED), electron microscopy, multiple Cep290 mutant mouse models JCI insight High 34520396
2025 CEP290 is distributed throughout the connecting cilium between microtubules and membrane with nine-fold symmetry. In CEP290-deficient mouse photoreceptors, the connecting cilium membrane is aberrant, the ciliary necklace and Y-links are confined to the proximal connecting cilium, and TZ proteins AHI1 and NPHP1 are abnormally restricted to the proximal CC while NPHP8 and CEP89 are unaffected. Outer segment disc formation is inhibited and large numbers of extracellular vesicles accumulate. Electron microscopy, immunofluorescence, advanced microscopy in Cep290 conditional KO mouse photoreceptors during development Journal of cell science High 40704549
2024 The Cep131-Cep162 module (near the axoneme) and the Cby-Fam92 module (close to the membrane) synergistically control the basal body localization of Cep290 and initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein from both modules causes complete loss of Cep290 from the basal body and blocks ciliogenesis at its initiation stage, demonstrating cooperative retroactive interactions converging on Cep290. Drosophila genetics (single and double deletion mutants), immunofluorescence, ciliogenesis initiation assays PLoS biology High 38442096
2021 In zebrafish cep290 genetic mutants (but not morpholino knockdowns), cilia-associated small GTPases arl3, arl13b, and unc119b are upregulated; ectopic expression of these genes rescues Kupffer's vesicle cilia and partially rescues photoreceptor outer segment defects in cep290 morphants. UNC119b upregulation was also observed in human Joubert syndrome CEP290 patient-derived renal epithelial cells, identifying lipidated protein trafficking to cilia as a compensatory pathway. Zebrafish CRISPR/morpholino, RNA-seq, ectopic overexpression rescue, human patient-derived cells Journal of cell science Medium 34155518
2011 Expression of only the N-terminal region of human CEP290 rescues the vision impairment caused by cep290 disruption in zebrafish, demonstrating that the N-terminal domain is sufficient to restore visual function and represents a minimal functional unit. Zebrafish morpholino knockdown, domain-specific rescue with human CEP290 fragments, visual function assay (optokinetic response) Human molecular genetics Medium 21257638
2018 CEP290 C-terminal domain (989 residues including the region deleted in rd16 mice) delivered by AAV complements the Cep290rd16 mutation in trans, reconstitutes CEP290 function, preserves cone photoreceptors, and delays rod death in Cep290rd16 mice and rd16;Nrl-/- mice; the same fragment also improves cilia phenotypes in mouse embryonic fibroblasts and iPSC-derived retinal organoids. AAV-mediated domain delivery, photoreceptor cell counting, ERG, cilia phenotype rescue in fibroblasts and iPSC organoids Cell reports High 30332642

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. American journal of human genetics 552 16909394
2006 Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nature genetics 316 16682970
2006 In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Human molecular genetics 313 16632484
2010 CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content. The Journal of cell biology 309 20819941
2008 CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. Human molecular genetics 244 18772192
2010 CEP290, a gene with many faces: mutation overview and presentation of CEP290base. Human mutation 242 20690115
2008 CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Developmental cell 220 18694559
2007 Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. American journal of human genetics 215 17564974
2008 CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. American journal of human genetics 184 18950740
2007 Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. Human mutation 169 17345604
2024 Gene Editing for CEP290-Associated Retinal Degeneration. The New England journal of medicine 146 38709228
2018 Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models. Molecular therapy. Nucleic acids 139 30114557
2007 High NPHP1 and NPHP6 mutation rate in patients with Joubert syndrome and nephronophthisis: potential epistatic effect of NPHP6 and AHI1 mutations in patients with NPHP1 mutations. Journal of the American Society of Nephrology : JASN 130 17409309
2007 Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 130 17898177
2007 Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. Human mutation 129 17554762
2007 CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. American journal of human genetics 126 17564967
2017 In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations. Cell reports 125 28700940
2012 Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290. Molecular therapy. Nucleic acids 122 23343883
2008 Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome. Human mutation 120 17705300
2016 In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery. Human molecular genetics 119 27106101
2012 Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins. Cilia 118 23351659
2012 The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium. Molecular biology of the cell 116 22767577
2010 Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. Human mutation 116 20683928
2016 MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone. PLoS biology 110 26982032
2014 CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype. Gene therapy 104 24807808
2011 Cone photoreceptors are the main targets for gene therapy of NPHP5 (IQCB1) or NPHP6 (CEP290) blindness: generation of an all-cone Nphp6 hypomorph mouse that mimics the human retinal ciliopathy. Human molecular genetics 102 21245082
2015 CEP290 alleles in mice disrupt tissue-specific cilia biogenesis and recapitulate features of syndromic ciliopathies. Human molecular genetics 99 25859007
2014 The CP110-interacting proteins Talpid3 and Cep290 play overlapping and distinct roles in cilia assembly. The Journal of cell biology 98 24421332
2013 BBS mutations modify phenotypic expression of CEP290-related ciliopathies. Human molecular genetics 95 23943788
2012 AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation. Molecular therapy. Nucleic acids 92 23344081
2007 Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior-Løken syndrome. Journal of medical genetics 90 17617513
2019 Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome. Journal of cellular and molecular medicine 82 31840411
2007 Mutation in CEP290 discovered for cat model of human retinal degeneration. The Journal of heredity 82 17507457
2014 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary trafficking and cargo delivery. Human molecular genetics 75 25552655
2013 Disruption of CEP290 microtubule/membrane-binding domains causes retinal degeneration. The Journal of clinical investigation 67 24051377
2012 Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis. The Journal of clinical investigation 67 22446187
2008 Genetic and physical interaction between the NPHP5 and NPHP6 gene products. Human molecular genetics 67 18723859
2010 A novel nonsense mutation in CEP290 induces exon skipping and leads to a relatively mild retinal phenotype. Investigative ophthalmology & visual science 64 20130272
2018 Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies. Ophthalmology 62 29398085
2018 Targeted exon skipping of a CEP290 mutation rescues Joubert syndrome phenotypes in vitro and in a murine model. Proceedings of the National Academy of Sciences of the United States of America 61 30446612
2013 Pathogenic NPHP5 mutations impair protein interaction with Cep290, a prerequisite for ciliogenesis. Human molecular genetics 60 23446637
2013 Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis. PloS one 58 24223178
2013 The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone. Molecular biology of the cell 55 24356449
2011 The N-terminal region of centrosomal protein 290 (CEP290) restores vision in a zebrafish model of human blindness. Human molecular genetics 53 21257638
2017 The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking. Journal of cell science 51 28235840
2017 Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the Intronic Mutation in the CEP290 Gene. Investigative ophthalmology & visual science 50 28510626
2020 CEP290 is essential for the initiation of ciliary transition zone assembly. PLoS biology 48 33370260
2015 DNA replication stress underlies renal phenotypes in CEP290-associated Joubert syndrome. The Journal of clinical investigation 48 26301811
2021 LEBER CONGENITAL AMAUROSIS DUE TO CEP290 MUTATIONS-SEVERE VISION IMPAIRMENT WITH A HIGH UNMET MEDICAL NEED: A Review. Retina (Philadelphia, Pa.) 45 33595255
2010 Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations. Journal of medical genetics 45 20805370
2013 Visual acuity changes in patients with leber congenital amaurosis and mutations in CEP290. JAMA ophthalmology 44 23411883
2012 Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290. Molecular vision 42 22355252
2012 Ciliary transition zone (TZ) proteins RPGR and CEP290: role in photoreceptor cilia and degenerative diseases. Expert opinion on therapeutic targets 42 22563985
2011 Accumulation of the Raf-1 kinase inhibitory protein (Rkip) is associated with Cep290-mediated photoreceptor degeneration in ciliopathies. The Journal of biological chemistry 38 21685394
2018 A CEP290 C-Terminal Domain Complements the Mutant CEP290 of Rd16 Mice In Trans and Rescues Retinal Degeneration. Cell reports 37 30332642
2016 Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR. Human molecular genetics 37 26936822
2022 Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites. Nature cell biology 36 35411088
2019 Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish. PloS one 33 30970040
2014 CEP290 and the primary cilium. Advances in experimental medicine and biology 33 24664739
2019 CEP290 Mutation Spectrum and Delineation of the Associated Phenotype in a Large German Cohort: A Monocentric Study. American journal of ophthalmology 32 31734136
2018 Antisense Oligonucleotide-Based Splicing Correction in Individuals with Leber Congenital Amaurosis due to Compound Heterozygosity for the c.2991+1655A>G Mutation in CEP290. International journal of molecular sciences 30 29518907
2018 Basal exon skipping and nonsense-associated altered splicing allows bypassing complete CEP290 loss-of-function in individuals with unusually mild retinal disease. Human molecular genetics 30 29771326
2021 Super-resolution microscopy reveals photoreceptor-specific subciliary location and function of ciliopathy-associated protein CEP290. JCI insight 29 34520396
2010 Ciliary trafficking: CEP290 guards a gated community. Current biology : CB 28 21056833
2009 Expanding CEP290 mutational spectrum in ciliopathies. American journal of medical genetics. Part A 28 19764032
2015 Species-dependent splice recognition of a cryptic exon resulting from a recurrent intronic CEP290 mutation that causes congenital blindness. International journal of molecular sciences 26 25761237
2014 Natural history of cone disease in the murine model of Leber congenital amaurosis due to CEP290 mutation: determining the timing and expectation of therapy. PloS one 25 24671090
2007 Frequency of CEP290 c.2991_1655A>G mutation in 175 Spanish families affected with Leber congenital amaurosis and early-onset retinitis pigmentosa. Molecular vision 25 18079693
2018 Searching the second hit in patients with inherited retinal dystrophies and monoallelic variants in ABCA4, USH2A and CEP290 by whole-gene targeted sequencing. Scientific reports 24 30190494
2021 Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases. Journal of cell science 23 34155518
2018 Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA. Molecular therapy. Nucleic acids 23 30195768
2023 Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models. Cells 22 37371046
2021 Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone. Molecular biology of the cell 22 33625872
2017 A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290. Genes 21 28829391
2019 AON-Mediated Exon Skipping to Bypass Protein Truncation in Retinal Dystrophies Due to the Recurrent CEP290 c.4723A > T Mutation. Fact or Fiction? Genes 20 31091803
2018 Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290. Investigative ophthalmology & visual science 18 30193310
2013 The BCG Moreau RD16 deletion inactivates a repressor reshaping transcription of an adjacent gene. Tuberculosis (Edinburgh, Scotland) 16 24332305
2012 Investigating embryonic expression patterns and evolution of AHI1 and CEP290 genes, implicated in Joubert syndrome. PloS one 16 23028714
2023 Durable vision improvement after a single intravitreal treatment with antisense oligonucleotide in CEP290-LCA: Replication in two eyes. American journal of ophthalmology case reports 14 37388818
2020 Transient pupillary light reflex in CEP290- or NPHP5-associated Leber congenital amaurosis: Latency as a potential outcome measure of cone function. Vision research 13 32088401
2018 A rare human CEP290 variant disrupts the molecular integrity of the primary cilium and impairs Sonic Hedgehog machinery. Scientific reports 13 30478281
2017 Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases. Brain & development 11 29217415
2013 12q21 Microdeletion in a fetus with Meckel syndrome involving CEP290/MKS4. European journal of medical genetics 10 23954617
2010 Effects of hereditary retinal degeneration due to a CEP290 mutation on the feline pupillary light reflex. Veterinary ophthalmology 10 20500714
2004 Subcellullar localization of tumor-associated antigen 3H11Ag. Biochemical and biophysical research communications 9 15474516
2020 A Mild Phenotype Caused by Two Novel Compound Heterozygous Mutations in CEP290. Genes 8 33105651
2024 Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation. PLoS biology 7 38442096
2014 Two novel mutations in the C-terminal region of centrosomal protein 290 (CEP290) result in classic Joubert syndrome. Journal of child neurology 7 24850569
2024 Twelve-month Natural History Study of Centrosomal Protein 290 (CEP290)-associated Inherited Retinal Degeneration. Ophthalmology science 6 38881603
2021 CEP104 and CEP290; Genes with Ciliary Functions Cause Intellectual Disability in Multiple Families. Archives of Iranian medicine 6 34196201
2021 Spectrum of Disease Severity in Nonsyndromic Patients With Mutations in the CEP290 Gene: A Multicentric Longitudinal Study. Investigative ophthalmology & visual science 6 34196655
2018 The ciliopathy gene product Cep290 is required for primary cilium formation and microtubule network organization. Turkish journal of biology = Turk biyoloji dergisi 6 30930621
2017 From disease modelling to personalised therapy in patients with CEP290 mutations. F1000Research 6 28690834
2015 Leber congenital amaurosis: first genotyped Hungarian patients and report of 2 novel mutations in the CRB1 and CEP290 genes. European journal of ophthalmology 6 26165328
2025 Sub-ciliary localization of CEP290 and effects of its loss in mouse photoreceptors during development. Journal of cell science 5 40704549
2022 Alternative splicing in CEP290 mutant cats results in a milder phenotype than LCACEP290 patients. Veterinary ophthalmology 5 36495011
2020 Investigation of CEP290 genotype-phenotype correlations in a patient with retinitis pigmentosa, infertility, end-stage renal disease, and a novel mutation. Ophthalmic genetics 5 32208788
2020 Novel biallelic loss-of-function variants in CEP290 cause Joubert syndrome in two siblings. Human genomics 5 32600475
2024 Spectrum and frequencies of extraocular features reported in CEP290-associated ciliopathy - A systematic review. Journal francais d'ophtalmologie 4 39213781
2023 Comparative analysis of transcriptional changes in zebrafish cep290 and bbs2 mutants by RNA-seq reveals upregulation of inflammatory and stress-related pathways. Frontiers in molecular neuroscience 4 37293546

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