Harmonin (USH1C)

Harmonin is a multi-PDZ domain scaffold protein encoded by the USH1C gene, playing a critical role in the development and structural maintenance of sensory hair cells in the inner ear and photoreceptor cells in the retina (UniProt Q9Y6N9). It acts as a central hub in the Usher protein network, interacting with molecules such as cadherin-23 and myosin VIIa to organize the stereocilia bundles required for mechanotransduction (PubMed: 11239468). Mutations in the USH1C gene are the underlying cause of Usher syndrome type 1C, which manifests as profound congenital hearing loss, vestibular dysfunction, and progressive vision loss due to retinitis pigmentosa (NIH: GARD). Because harmonin is a structural scaffold rather than an enzyme, it is targeted therapeutically through genetic approaches. Current research focuses on antisense oligonucleotides (ASOs) to correct splicing errors and adeno-associated virus (AAV) vectors for gene replacement, aiming to restore functional protein levels and preserve sensory function (PubMed: 23396103, 28244866).

Other names

PDZ domain-containing protein USH1CAntigenic in intestine epitope 75AIE-75Usher syndrome type-1C proteinDFNB18

Splice-switching antisense oligonucleotides (ASOs) target specific pre-mRNA mutations (such as the c.216G>A founder mutation) to restore correct splicing and functional protein expression; gene therapy utilizes viral vectors to deliver a functional copy of the USH1C gene to sensory cells.