Harmonin (USH1C) (USH1C)

Harmonin, encoded by the USH1C gene, is a multi-PDZ domain scaffold protein essential for the structural integrity and function of sensory hair cells in the inner ear and photoreceptor cells in the retina (UniProt Q9Y6N9). In retinal cells, harmonin is localized to the photoreceptor connecting cilium and synaptic terminals, where it coordinates protein networks involved in intracellular transport and signal transduction (PubMed: 21822275). Deficiency of functional harmonin, typically due to autosomal recessive mutations, results in Usher syndrome type 1C, a condition characterized by profound deafness and progressive blindness from retinitis pigmentosa (NIH: Genetic Home Reference). Therapeutic approaches currently under investigation include gene replacement therapy using adeno-associated virus (AAV) vectors and antisense oligonucleotides (ASOs) designed to correct specific splicing mutations, such as the c.216G>A Acadian mutation (PubMed: 28165461). These interventions aim to restore harmonin expression to prevent or delay retinal degeneration and hearing loss by stabilizing the Usher protein network within the eye.

Other names

PDZ domain-containing protein USH1CUsher syndrome type-1C proteinAIE-75DFNB18NY-CO-38PDZ-73

Restoration of functional harmonin protein levels through adeno-associated virus (AAV) mediated gene replacement or the use of antisense oligonucleotides (ASOs) to correct pre-mRNA splicing defects, specifically targeting the c.216G>A mutation.