Centrosomal protein of 290 kDa (CEP290) (CEP290)

The centrosomal protein of 290 kDa (CEP290) is a large protein encoded by the CEP290 gene on chromosome 12q, localized primarily to centrosomes and cilia, where it plays a critical role in ciliogenesis and the formation of primary cilia—antenna-like structures essential for sensory perception in photoreceptors, kidney cells, and neurons. CEP290 facilitates microtubule-membrane tethering at the ciliary transition zone, regulates intraflagellar transport (IFT) complexes, and supports the structural integrity of cilia by interacting with proteins like CP110 and components of the BBSome. Mutations in CEP290, such as the common intronic variant 2991+1655A>G, lead to truncated or dysfunctional protein, disrupting cilia function and causing severe ciliopathies. It is a leading cause of Leber congenital amaurosis (LCA10, 15-22% of cases), resulting in infantile blindness due to photoreceptor defects, and is implicated in pleiotropic syndromes like Joubert, Meckel-Gruber, Bardet-Biedl, and Senior-Løken syndromes affecting retina, brain, kidneys, and other organs. While not yet a direct small-molecule drug target, CEP290 mutations are under investigation for gene therapy in retinal ciliopathies, with preclinical models showing ciliogenesis rescue potential. The protein's coiled-coil domains and binding motifs enable its roles in microtubule organization and protein trafficking, but its deficiency causes broad ciliary dysfunction explaining diverse phenotypes.

Other names

centrosomal protein 290 kDanephrocystin-6 (NPHP6)Bardet-Biedl syndrome 14 protein (BBS14)Meckel syndrome 4 protein (MKS4)Joubert syndrome 5 protein (JBTS5)Leber congenital amaurosis 10 protein (LCA10)cancer/testis antigen 87 (CT87)tumor antigen se2-2CTCL tumor antigen se2-2prostate cancer antigen T21monoclonal antibody 3H11 antigenPOC3 centriolar protein homolog