Usher syndrome type-2A protein (USH2A)

Usherin, encoded by the USH2A gene, is a large basement membrane-like transmembrane protein essential for the structural and functional integrity of sensory cells in the inner ear and the retina (UniProt Q9Y646). In the cochlea, it is a vital component of the protein complex forming the hair cell stereocilia ankle links, which are necessary for mechanotransduction and hearing (PubMed: 20301591). In the eye, usherin is localized to the photoreceptor periciliary membrane, where it facilitates the transport of essential proteins between the inner and outer segments (NIH: GeneReviews). Mutations in the USH2A gene are the most common cause of Usher syndrome, a condition characterized by combined hearing loss and progressive vision loss due to retinitis pigmentosa (PubMed: 33513348). Because the USH2A cDNA is too large for standard single-vector adeno-associated virus (AAV) gene replacement, therapeutic development has shifted toward antisense oligonucleotides (ASOs) like ultevursen, which aim to skip specific mutation-bearing exons to restore protein function (ClinicalTrials.gov: NCT03913169). Current clinical efforts focus on slowing the progression of retinal degeneration in patients with specific USH2A mutations.

Other names

UsherinUSH2US2Usher syndrome type IIa protein

Antisense oligonucleotide-mediated exon skipping to restore the reading frame and produce a functional truncated protein