CEP290

This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]

Centrosomal Protein 290

Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559).
May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332).
Required for the correct localization of ciliary and phototransduction proteins in retinal photoreceptor cells; may play a role in ciliary transport processes (By similarity).
Required for efficient recruitment of RAB8A to primary cilium (PubMed:17705300).
In the ciliary transition zone is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity).
Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2, BBS5 and BBS8/TTC8 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating IQCB1/NPHP5 (PubMed:25552655).
Activates ATF4-mediated transcription (PubMed:16682973).

Ciliary basal body-plasma membrane docking Source: Reactome
Cilium assembly Source: UniProtKB
Eye photoreceptor cell development Source: HGNC-UCL
G2/M transition of mitotic cell cycle Source: Reactome
Hindbrain development Source: HGNC-UCL
Neutrophil degranulation Source: Reactome
Otic vesicle formation Source: HGNC-UCL
Positive regulation of intracellular protein transport Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: HGNC-UCL
Pronephros development Source: HGNC-UCL
Protein transport Source: UniProtKB
Regulation of establishment of protein localization Source: MGI
Regulation of G2/M transition of mitotic cell cycle Source: Reactome

Nucleus; Centrosome; Centriolar satellite; Cilium basal body; Centriole; Cilium; Cytoplasmic vesicle. Displaced from centriolar satellites in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock (PubMed:24121310). Found in the connecting cilium of photoreceptor cells, base of cilium in kidney intramedullary collecting duct cells (By similarity). Localizes at the transition zone, a region between the basal body and the ciliary axoneme (PubMed:23943788). Localization at the ciliary transition zone as well as at centriolar satellites is BBsome-dependent (PubMed:23943788).

Joubert syndrome 5 (JBTS5): A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis.
Senior-Loken syndrome 6 (SLSN6): A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.
Leber congenital amaurosis 10 (LCA10):
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Meckel syndrome 4 (MKS4): A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.
Antibodies against CEP290 are present in sera from patients with cutaneous T-cell lymphomas, but not in the healthy control population.
Bardet-Biedl syndrome 14 (BBS14): A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease.

Ubiquitinated. May undergo monoubiquitination; monoubiquitination is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, but does not cause it displacement from centriolar satellites.