Affinage

CEP290

Centrosomal protein of 290 kDa · UniProt O15078

Length
2479 aa
Mass
290.4 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP290 is a large coiled-coil centrosomal and ciliary protein that functions as a central organizer of the transition zone and a selective gatekeeper controlling the entry and exit of signaling molecules into cilia. It localizes with nine-fold symmetry between axonemal microtubule doublets and the ciliary membrane at the Y-linker region, directly binding microtubules via a myosin-tail homology domain and cellular membranes via an N-terminal amphipathic helix; its activity is regulated by N- and C-terminal autoinhibitory domains (PMID:24051377, PMID:20819941, PMID:40704549). CEP290 initiates transition zone assembly by recruiting DZIP1, Chibby, and Rab8, interacts with PCM-1 at centriolar satellites to regulate BBSome trafficking, and forms functionally important complexes with NPHP5, CP110, RPGR, CC2D2A, and MKKS; loss of CEP290 disrupts the ciliary diffusion barrier, causing selective mislocalization of signaling proteins such as ARL13B, ADCY3, Smoothened, and GPR161 and augmented Hedgehog signaling (PMID:33370260, PMID:18772192, PMID:28700940, PMID:26982032). Mutations in CEP290 cause Joubert syndrome and allied ciliopathies including retinal degeneration, nephronophthisis, and cerebellar malformations, and CEP290 deficiency additionally induces DNA replication stress with increased DNA damage, supernumerary centrioles, and decreased replication fork velocity that are rescued by CDK inhibition (PMID:16682970, PMID:26301811).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    Identification of CEP290 as a centrosomal/ciliary protein whose mutation causes ciliopathy established the gene as a ciliary transport regulator and linked it to Joubert syndrome.

    Evidence Immunolocalization, immunogold EM, co-IP with RPGR in mouse retina; expression analysis in cerebellar granule neurons with patient mutation screening

    PMID:16632484 PMID:16682970

    Open questions at the time
    • Molecular mechanism of CEP290-RPGR interaction unresolved
    • Subciliary localization not yet resolved at nanoscale
  2. 2007 High

    Demonstration that CEP290 selectively mediates G protein trafficking into olfactory cilia revealed it acts as a cargo-selective gate rather than a general transport factor.

    Evidence Electro-olfactograms, co-IP with Golf/Gγ13, immunofluorescence in rd16 mouse olfactory neurons

    PMID:17898177

    Open questions at the time
    • How CEP290 discriminates between cargo proteins unknown
    • Structural basis for selectivity unresolved
  3. 2008 High

    A series of studies mapped CEP290 into a physical interaction network with PCM-1, CP110, NPHP5, CC2D2A, and Rab8a, establishing it as a hub connecting centriolar satellites, the mother centriole cap, and ciliogenesis initiation.

    Evidence Reciprocal co-IP, domain mapping, siRNA knockdown with ciliogenesis and Rab8 localization assays, yeast two-hybrid, GST pull-down, zebrafish genetic epistasis

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

    Open questions at the time
    • Stoichiometry and temporal order of complex assembly at the basal body undefined
    • Whether CP110-CEP290 and PCM1-CEP290 complexes coexist or are mutually exclusive unclear
  4. 2010 High

    Ultrastructural analysis in Chlamydomonas established that CEP290 forms the physical microtubule-membrane links at the transition zone and controls flagellar protein composition, providing the first structural evidence for its gatekeeper role.

    Evidence Immunoelectron microscopy, biochemical fractionation of isolated flagella, dikaryon rescue in CEP290-deletion Chlamydomonas

    PMID:20819941

    Open questions at the time
    • Whether the same ultrastructural role is conserved in vertebrate TZ not yet shown at this point
    • Molecular architecture of the Y-link with CEP290 unresolved
  5. 2012 High

    Discovery that CEP290 at centriolar satellites controls BBSome ciliary entry (via Cep72) and that CEP290-MKKS interaction modulates TZ complex integrity revealed how CEP290 coordinates satellite dynamics with ciliary trafficking.

    Evidence Co-IP, siRNA and zebrafish knockdown, mouse double-mutant crosses (Cep290rd16 × Mkks-ko)

    PMID:22446187 PMID:22767577

    Open questions at the time
    • How MKKS-CEP290 balance is mechanistically set at the TZ unknown
    • Whether satellite-independent CEP290 functions exist at the TZ not distinguished
  6. 2013 High

    Biochemical reconstitution revealed CEP290 directly binds membranes via an N-terminal amphipathic helix and microtubules via a myosin-tail homology domain, with two autoinhibitory domains regulating these activities, providing the first molecular-level mechanism for its bridge function.

    Evidence In vitro membrane-binding and microtubule-binding assays, domain mutagenesis, mouse genetic model with retinal degeneration

    PMID:24051377

    Open questions at the time
    • Structural basis for autoinhibition and its relief unknown
    • Whether post-translational modifications regulate domain switching untested
  7. 2013 High

    Multiple studies defined the BBSome-CEP290-NPHP5 axis: BBS4 binds CEP290 N-terminus; CEP290 and NPHP5 jointly maintain BBSome integrity and are placed in the same early ciliogenic pathway by pharmacological epistasis.

    Evidence Co-IP, domain mapping, mouse genetic epistasis (Cep290rd16 × Bbs4-null), pharmacological rescue screens, ciliary cargo assays

    PMID:23446637 PMID:23943788 PMID:25552655

    Open questions at the time
    • Whether CEP290 acts catalytically or purely as a scaffold for BBSome assembly unclear
    • Direct structural complex of CEP290-NPHP5-BBSome not reconstituted
  8. 2015 High

    CEP290 was localized precisely to the Y-linker substructure of the transition zone, and CEP290 depletion was found to cause DNA replication stress independent of its ciliary role, revealing a nuclear/cell-cycle function.

    Evidence Immunofluorescence and EM in mouse knockout; DNA fiber assays, γH2AX staining, CDK inhibitor rescue in kidney cells and zebrafish

    PMID:25859007 PMID:26301811

    Open questions at the time
    • Mechanism by which CEP290 regulates replication fork stability unknown
    • Whether nuclear CEP290 function is direct or mediated by centriole/centrosome defects unresolved
  9. 2016 High

    C. elegans epistasis hierarchies showed CEP290 is a central MKS-module assembly factor that prevents inappropriate entry of membrane-associated proteins and leakage of ARL-13 from cilia, consolidating the gatekeeper model across species.

    Evidence C. elegans genetic deletions, localization hierarchy mapping, fluorescent ciliary gating reporters

    PMID:26982032

    Open questions at the time
    • Whether CEP290 physically contacts each MKS component or acts indirectly not distinguished
    • Gating selectivity mechanism at molecular level unknown
  10. 2017 High

    Patient-derived cells demonstrated that CEP290 loss selectively reduces ciliary ADCY3 and ARL13B while augmenting Smoothened and GPR161 transport, confirming bidirectional gatekeeper function in human disease-relevant tissue.

    Evidence iPSC-derived optic cups and fibroblasts from Joubert syndrome patients, Hedgehog signaling assays

    PMID:28700940

    Open questions at the time
    • Whether augmented Hedgehog signaling directly drives cerebellar phenotype not tested
    • Mechanism discriminating cargo allowed vs. excluded at the gate unknown
  11. 2020 High

    Drosophila studies defined the earliest CEP290-dependent step in TZ assembly: the N-terminus recruits DZIP1, which then recruits Chibby and Rab8 to initiate ciliary membrane formation, ordering the pathway.

    Evidence Drosophila genetics, domain-specific expression rescue, immunofluorescence

    PMID:33370260

    Open questions at the time
    • Whether DZIP1 recruitment mechanism is conserved in vertebrates not shown
    • How N-terminal membrane binding and DZIP1 recruitment are coordinated unresolved
  12. 2021 High

    Super-resolution microscopy resolved CEP290 distribution throughout the connecting cilium of photoreceptors with nine-fold symmetry, and showed that severe deficiency reduces cilia number but does not prevent initial Y-link assembly, refining the structural model.

    Evidence STORM/STED, electron microscopy, multiple Cep290-deficient mouse models

    PMID:34520396

    Open questions at the time
    • Atomic-resolution structure of CEP290 within Y-links unresolved
    • Whether nine-fold arrangement requires oligomerization partners not determined
  13. 2024 High

    Cooperative recruitment of CEP290 to the basal body by axoneme-proximal (Cep131-Cep162) and membrane-proximal (Cby-Fam92) modules was defined, explaining how CEP290 is positioned between microtubules and membrane.

    Evidence Drosophila double-mutant genetic analysis with immunofluorescence

    PMID:38442096

    Open questions at the time
    • Whether these modules have vertebrate functional equivalents not tested
    • Direct physical contacts between modules and CEP290 domains not mapped
  14. 2025 High

    Advanced EM in Cep290-mutant mouse retinas showed that ciliogenesis still occurs without CEP290 but the connecting cilium membrane is aberrant, Y-links and TZ proteins are confined proximally, disc formation is blocked, and extracellular vesicles accumulate, demonstrating CEP290 extends TZ organization along the cilium length.

    Evidence Advanced electron microscopy with developmental time-course in Cep290-mutant mouse retinas

    PMID:40704549

    Open questions at the time
    • Whether ectopic vesicle release is a direct consequence of lost gating or membrane instability unclear
    • Whether pharmacological approaches can restore TZ extension untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic structure of CEP290 within the transition zone, the precise mechanism by which it discriminates between allowed and excluded ciliary cargoes, and the molecular basis of its nuclear/replication stress function remain unresolved.
  • No high-resolution structural model of full-length CEP290 or its TZ complex exists
  • Cargo selectivity mechanism unknown at molecular level
  • Nuclear function of CEP290 not distinguished from indirect centriolar/centrosomal effects

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0008289 lipid binding 1
Localization
GO:0005929 cilium 7 GO:0005815 microtubule organizing center 5 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 7 R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3 R-HSA-73894 DNA Repair 1
Partners
BBS4CC2D2ACP110DZIP1MKKSNPHP5PCM1RPGR
Complex memberships
CP110-CEP97-CEP290MKS module (transition zone)PCM1-CEP290 centriolar satellite complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CEP290 localizes to centrosomes in dividing cells and to the connecting cilium of retinal photoreceptors, where it associates with microtubule-based transport proteins including RPGR; an in-frame deletion in CEP290 (rd16 mouse) causes stronger association with specific RPGR isoforms and redistribution of RPGR and phototransduction proteins in photoreceptors, implicating CEP290 in ciliary transport. Immunolocalization, co-immunoprecipitation, immunogold electron microscopy, mouse genetic model Human molecular genetics High 16632484
2006 CEP290 expression shows centrosome and ciliary localization, linking it to ciliopathies; mutations in CEP290 cause pleiotropic Joubert syndrome features including cerebellar, retinal, and renal manifestations. Expression analysis, immunolocalization in cerebellar granule neurons Nature genetics Medium 16682970
2008 CEP290 physically 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 protein complex formation, disorganizes the cytoplasmic microtubule network, impairs ciliogenesis, and prevents ciliary targeting of Rab8. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliogenesis assays Human molecular genetics High 18772192
2008 CP110 interacts with CEP290 in a discrete complex separable from other CP110 complexes; this interaction is required for CP110 to suppress primary cilia formation; CEP290 and CP110 also interact with Rab8a, and depletion of CEP290 prevents Rab8a localization to centrosomes and cilia, blocking ciliogenesis without affecting centrosome function or cell-cycle progression. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliogenesis assays Developmental cell High 18694559
2008 CC2D2A physically interacts with CEP290 at the basal body as shown by yeast two-hybrid and GST pull-down; knockdown of cep290 in cc2d2a-mutant zebrafish produces a synergistic pronephric cyst phenotype, revealing a genetic interaction between the two proteins. Yeast two-hybrid, GST pull-down, zebrafish genetic epistasis American journal of human genetics High 18950740
2008 The N-terminal domain of nephrocystin-6 (CEP290) directly binds nephrocystin-5 (NPHP5); mapping studies delineated the interaction site to amino acids 696–896 of NPHP6; expression of the nephrocystin-5-binding fragment of nephrocystin-6 in Xenopus phenocopies NPHP5 knockdown and is rescued by co-expression of nephrocystin-5, supporting a physical interaction in vivo; N- and C-terminal fragments of nephrocystin-6 form homo- and heteromeric complexes. Co-immunoprecipitation, domain mapping, Xenopus morpholino knockdown and rescue, zebrafish knockdown Human molecular genetics High 18723859
2010 In Chlamydomonas, CEP290 is located in the flagellar transition zone in close association with microtubule-membrane links; deletion of CEP290 causes loss of attachment of the flagellar membrane to transition zone microtubules, produces abnormal flagellar protein content (including IFT proteins and ciliopathy-associated proteins), and CEP290 at the transition zone undergoes rapid turnover. CEP290 is required to form microtubule-membrane linkers and to control flagellar protein composition. Immunoelectron microscopy, ultrastructural analysis, biochemical fractionation of isolated flagella, dikaryon experiments The Journal of cell biology High 20819941
2007 In olfactory sensory neurons, CEP290 localizes to dendritic knobs and is in complex with ciliary transport proteins and olfactory G proteins Golf and Gγ13; hypomorphic CEP290 mutation (rd16) causes selective loss of ciliary localization of Golf and Gγ13 but not of odorant receptors or other signaling components, implicating CEP290 as a key mediator of selective G protein trafficking into olfactory cilia. Electro-olfactogram recordings, co-immunoprecipitation, immunofluorescence, mouse genetic model Proceedings of the National Academy of Sciences of the United States of America High 17898177
2012 Cep72 is required for recruitment of CEP290 to centriolar satellites; interactions between PCM1, Cep72, and Cep290 were identified; disruption of centriolar satellites impairs ciliary localization of BBS4 in a Cep290- and Cep72-dependent manner, indicating that Cep290 and Cep72 in centriolar satellites regulate ciliary localization of the BBSome. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, zebrafish loss-of-function Molecular biology of the cell High 22767577
2013 CEP290 directly binds cellular membranes through an N-terminal amphipathic helix domain and binds microtubules through a domain within its myosin-tail homology domain; CEP290 activity is regulated by two autoinhibitory domains in its N and C termini; disruption of the microtubule-binding domain in a mouse model induces cilia formation deficits leading to retinal degeneration. In vitro membrane-binding assay, microtubule-binding assay, domain mutagenesis, mouse genetic model The Journal of clinical investigation High 24051377
2013 The BBSome binds to the N-terminal region of CEP290 through BBS4 and co-localizes with CEP290 at the transition zone, centriolar satellites, and connecting cilium; in BBSome-depleted cells, CEP290 localization to centriolar satellites is disrupted; genetic interaction was demonstrated: additional loss of Bbs4 alleles in Cep290rd16 mice accelerates photoreceptor degeneration and increases body weight, and double-heterozygous mice show increased body weight. Co-immunoprecipitation, immunofluorescence, mouse genetic epistasis (Cep290rd16 × Bbs4-null crosses) Human molecular genetics High 23943788
2012 The domain deleted in the Cep290rd16 protein directly interacts with MKKS; MKKS mutations found in Bardet-Biedl syndrome patients disrupt this interaction; combined subminimal knockdown of mkks and cep290 in zebrafish produces synergistic sensory defects; combinations of Cep290rd16 and Mkksko alleles in mice led to improved ciliogenesis and sensory functions compared with either mutant alone, suggesting that CEP290–MKKS interaction affects integrity of multiprotein complexes at the cilia transition zone. Co-immunoprecipitation, zebrafish genetic epistasis, mouse double-mutant crosses, ciliogenesis assays The Journal of clinical investigation High 22446187
2013 CEP290 depletion leads to accumulation of its novel interacting partner Rkip (Raf-1 kinase inhibitory protein); ectopic accumulation of Rkip causes defective cilia formation mediated by its interaction with the ciliary GTPase Rab8A, suggesting that Rkip prevents cilia formation downstream of CEP290. Co-immunoprecipitation, zebrafish morpholino knockdown, cell-based ciliogenesis assays, rd16 mouse model The Journal of biological chemistry Medium 21685394
2014 NPHP5 contains two separate BBS-binding sites and interacts with the BBSome; Cep290 directly binds NPHP5, and depletion of Cep290 causes dissociation of BBS8 from the BBSome and loss of ciliary BBS8 in addition to the BBS2/5 loss caused by NPHP5 depletion; selective impairment of BBSome cargo (smoothened, VPAC2, Rab8a) delivery to cilia occurs upon NPHP5 or Cep290 loss. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliary cargo trafficking assays Human molecular genetics High 25552655
2013 Pathogenic NPHP5 truncating mutations produce products unable to bind Cep290 and unable to localize to centrosomes, thereby blocking cilia formation; drugs antagonizing negative regulators of ciliogenesis rescue ciliation in NPHP5-depleted cells with response profiles similar to those of Cep290-depleted cells, placing NPHP5 and Cep290 in the same early ciliogenic pathway. Co-immunoprecipitation, domain mutagenesis, siRNA knockdown, pharmacological rescue, ciliogenesis assays Human molecular genetics High 23446637
2016 In C. elegans, CEP-290 is a central assembly factor specific to MKS module components at the transition zone, depending on the coiled-coil region of MKS-5 (RPGRIP1L) for TZ localization; CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and prevents ARL-13 from leaking out of cilia; CEP-290-dependent TZ localization was established for TMEM-218, TMEM-138, and CDKL-1. C. elegans genetic deletion, immunofluorescence localization hierarchies, fluorescent protein reporters for ciliary gating PLoS biology High 26982032
2015 CEP290 localizes precisely to the transition zone Y-linker region between central microtubules and plasma membrane; Cep290ko/ko mice lacking CEP290 protein have photoreceptors that lack connecting cilia and fail to mature ciliated ventricular ependyma; partial loss of CEP290-interacting ciliopathy protein MKKS mitigates lethality and renal pathology in Cep290gt/gt mice, indicating domain-specific genetic interactions. Immunofluorescence, mouse genetic knockout, light and electron microscopy Human molecular genetics High 25859007
2016 Phenotypic expression of Rpgr-loss in mice is modified by heterozygous hypomorphic but not null alleles of Cep290; physical interaction between RPGR and the C-terminal domain of CEP290 was demonstrated; Rpgrko/Y::Cep290rd16/+ mice show early-onset retinal degeneration with disorganized outer segments and defective opsin trafficking. Co-immunoprecipitation, mouse double-mutant crosses, immunofluorescence, electroretinography Human molecular genetics High 26936822
2015 DNA replication stress underlies renal phenotypes in CEP290-associated ciliopathy; reduction of CEP290 in kidney cells and zebrafish leads to enhanced DNA damage signaling, DNA breaks, supernumerary centrioles, decreased replication fork velocity, fork asymmetry, and increased CDK levels; CDK inhibitor treatment rescues DNA damage, centriole number, and primary cilia loss in Cep290-deficient cells. DNA fiber assay, γH2AX staining, CDK inhibitor treatment, 3D spheroid culture, zebrafish knockdown The Journal of clinical investigation High 26301811
2017 CEP290 acts as a selective ciliary gatekeeper: in JSRD patient fibroblasts lacking CEP290, cilia are abnormal with decreased ciliogenesis and selectively reduced localization of ADCY3 and ARL13B; Hedgehog signaling is augmented due to enhanced ciliary transport of Smoothened and GPR161, demonstrating that CEP290 controls selective entry and exit of signaling molecules at the ciliary gate. iPSC-derived optic cups and fibroblasts from patients, immunofluorescence, ciliogenesis quantification, Hedgehog signaling assays Cell reports High 28700940
2013 SSX2IP localizes to the basal body of primary cilia and is required for efficient recruitment of Cep290 to centriolar satellites and the basal body; loss of SSX2IP impairs BBSome entry into cilia, reduces Rab8 accumulation, and reduces ciliary targeting of somatostatin receptor 3. siRNA knockdown, immunofluorescence, co-immunoprecipitation Molecular biology of the cell Medium 24356449
2017 CCDC66 is a centriolar satellite protein that interacts with CEP290 and PCM1 as shown by co-immunoprecipitation; depletion of CCDC66 impairs ciliogenesis, ciliary recruitment of BBS4, and centriolar satellite organization. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, ciliogenesis assays Journal of cell science Medium 28235840
2014 Talpid3 and Cep290 play overlapping and distinct roles in cilia formation: both affect Rab8a localization and centriolar satellite dynamics; ultrastructural analyses show Talpid3 is required for centriolar satellite dispersal preceding mature ciliary vesicle formation, a process requiring Cep290; expression of activated Rab8a suppresses cilia assembly defects caused by Talpid3 depletion. siRNA knockdown, immunofluorescence, electron microscopy, activated Rab8a rescue The Journal of cell biology High 24421332
2018 A CEP290 C-terminal fragment (989 residues including the domain deleted in rd16 mice) delivered by AAV complements mutant CEP290 in trans, rescuing cone preservation, delaying rod death, improving cilia phenotypes in mouse embryonic fibroblasts, and improving photoreceptor outer segments in iPSC-derived retinal organoids. AAV gene delivery, mouse in vivo rescue (Cep290rd16 and rd16;Nrl-/- models), electroretinography, histology, iPSC-derived organoids Cell reports High 30332642
2011 The N-terminal region of human CEP290 protein is sufficient to restore visual function in cep290 morpholino-injected zebrafish; cep290 morphants exhibit reduced Kupffer's vesicle size and delayed melanosome transport phenotypes similar to bbs knockdowns. Zebrafish morpholino knockdown, mRNA rescue, visual function assay Human molecular genetics Medium 21257638
2020 In Drosophila, the N-terminus of CEP290 directly recruits DZIP1, which then recruits Chibby and Rab8 to promote early ciliary membrane formation; complete deletion of CEP290 blocks ciliogenesis at the transition zone assembly initiation stage, phenocopied by DZIP1 deletion; expression of CEP290 N-terminus alone restores DZIP1 TZ localization and ameliorates TZ assembly initiation defects. Drosophila genetics, in vivo rescue, immunofluorescence, domain-specific expression PLoS biology High 33370260
2021 Rpgrip1l controls ciliary gating by ensuring the proper amount of CEP290 at the vertebrate transition zone; reduction of Rpgrip1l leads to decreased CEP290 at the TZ; the flavonoid eupatilin rescues ciliary gating defects caused by Rpgrip1l loss. Immunofluorescence in mouse and zebrafish models, pharmacological rescue Molecular biology of the cell Medium 33625872
2021 Using super-resolution fluorescence microscopy, CEP290 localizes radially between microtubule doublets and the ciliary membrane throughout the full length of the connecting cilium in photoreceptors, but is confined to the very base of primary cilia in RPE1 cells; severe CEP290 deficiency reduces cilia number and prevents normal outer segment formation but does not prevent assembly of Y-shaped links in early stages. Super-resolution fluorescence microscopy (STORM/STED), electron microscopy, CEP290-deficient mouse models JCI insight High 34520396
2022 During aggresome assembly, the seeding of an initial phosphorylated HSP27 ring at the centrosome depends on CP110, CEP97, and CEP290; centriolar satellites are required for aggresome growth from this ring; CP110-CEP97-CEP290 and satellites are also required for aggregation of mutant huntingtin. High-resolution quantitative microscopy, siRNA knockdown, aggresome formation assays in human cells Nature cell biology Medium 35411088
2025 Using advanced microscopy, CEP290 is found throughout the connecting cilium with nine-fold symmetry between microtubules and membrane; in the absence of CEP290, ciliogenesis occurs but the connecting cilium membrane is aberrant, ciliary necklace and Y-links are confined to the proximal connecting cilium, TZ proteins AHI1 and NPHP1 are abnormally restricted to the proximal connecting cilium, outer segment disc formation is inhibited, and large numbers of extracellular vesicles form. Advanced electron microscopy, immunofluorescence, Cep290 mutant mouse retinas, developmental time-course 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 basal body localization of CEP290 and ciliogenesis initiation 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. Drosophila genetics, immunofluorescence, double-mutant analysis PLoS biology High 38442096
2018 A rare CEP290 missense variant (R1747Q/R1746Q) disrupts the ciliary diffusion barrier, causes mislocalization of the Shh receptor Smoothened, dysregulates ciliary protein mobility, and impairs proliferation of cerebellar granule progenitors; confirmed in an autism patient-derived iPSC line. FRAP, immunofluorescence, Hedgehog signaling assays, mouse and iPSC models Scientific reports Medium 30478281

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 312 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 243 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
2018 Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models. Molecular therapy. Nucleic acids 138 30114557
2024 Gene Editing for CEP290-Associated Retinal Degeneration. The New England journal of medicine 136 38709228
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 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 129 17409309
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 125 17564967
2017 In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations. Cell reports 123 28700940
2012 Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290. Molecular therapy. Nucleic acids 121 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 118 27106101
2012 Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins. Cilia 118 23351659
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
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 115 22767577
2016 MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone. PLoS biology 108 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 97 24421332
2013 BBS mutations modify phenotypic expression of CEP290-related ciliopathies. Human molecular genetics 94 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
2007 Mutation in CEP290 discovered for cat model of human retinal degeneration. The Journal of heredity 82 17507457
2019 Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome. Journal of cellular and molecular medicine 80 31840411
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 61 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 49 28510626
2015 DNA replication stress underlies renal phenotypes in CEP290-associated Joubert syndrome. The Journal of clinical investigation 48 26301811
2020 CEP290 is essential for the initiation of ciliary transition zone assembly. PLoS biology 46 33370260
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
2016 Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR. Human molecular genetics 37 26936822
2018 A CEP290 C-Terminal Domain Complements the Mutant CEP290 of Rd16 Mice In Trans and Rescues Retinal Degeneration. Cell reports 36 30332642
2022 Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites. Nature cell biology 33 35411088
2014 CEP290 and the primary cilium. Advances in experimental medicine and biology 33 24664739
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 32 30970040
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
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
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 24 24671090
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
2021 Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases. Journal of cell science 22 34155518
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
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
2025 Sub-ciliary localization of CEP290 and effects of its loss in mouse photoreceptors during development. Journal of cell science 4 40704549
2024 Spectrum and frequencies of extraocular features reported in CEP290-associated ciliopathy - A systematic review. Journal francais d'ophtalmologie 4 39213781
2022 Evaluation of novel compound variants of CEP290 in prenatally suspected case of Meckel syndrome through whole exome sequencing. Molecular genetics & genomic medicine 4 35352487