CEP290 (Centrosomal Protein 290 Photoreceptor Ciliary Gatekeeper)
CEP290 (centrosomal protein 290; HGNC:29021, NCBI Gene ID 80184) is a human locus mapped to chromosome band 12q21.32 that encodes centrosomal and ciliary transition-zone scaffolding protein CEP290 (2,479 aa). CEP290 acts in primary cilium transition-zone assembly & photoreceptor outer-segment trafficking, together with Rhodopsin (RHO Photoreceptor), RPE65 (Retinoid Isomerohydrolase Gene), and CRISPR-Cas9 Genome Editing. Encodes the centrosomal/ciliary transition-zone protein mutated in Leber congenital amaurosis type 10.
Approved Symbol
CEP290
Chromosomal Locus
12q21.32
Encoded Product
Centrosomal and ciliary transition-zone scaffolding protein CEP290 (2,479 aa)
Genomic Organization & Cytogenetic Locus: 54-exon gene spanning ~93 kb at 12q21.32, encoding a 2,479-amino-acid coiled-coil scaffolding protein (~290 kDa) whose 7.4 kb coding sequence exceeds the 4.7 kb packaging capacity of standard single adeno-associated virus (AAV) capsids.
Cellular & Tissue Expression Profile: Localized at the centrosome of dividing cells and specifically at the Y-linkers of the ciliary transition zone in retinal rod and cone photoreceptors, renal tubular epithelial cells, and cerebellar granule neurons.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Tethers the axonemal microtubule doublets to the ciliary membrane at the photoreceptor connecting cilium, acting as a molecular diffusion barrier and Rab8a/BBSome docking hub required to transport rhodopsin (RHO) and phototransduction proteins into the outer segment.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: The most frequent cause of Leber congenital amaurosis type 10 (LCA10) is the recurrent deep-intronic mutation c.2991+1655A>G in intron 26, which creates a cryptic splice donor site that inserts a 128-bp pseudoexon (exon X) containing a premature stop codon (p.Cys998Ter), while null alleles cause severe syndromic ciliopathies including Joubert, Senior-Loken, and Meckel syndromes.
Therapeutic & Clinical Pharmacology: Landmark clinical testbed for nucleic acid therapeutics: targeted by the intravitreal splice-switching antisense oligonucleotide sepofarsen (QR-110) and by EDIT-101, the first in vivo CRISPR-Cas9 therapy administered directly into the human body (using dual SaCas9 guide RNAs to excise the intronic c.2991+1655A>G mutation).