Otoferlin (OTOF) (OTOF)

Otoferlin is a large transmembrane protein primarily expressed in the inner hair cells (IHCs) of the cochlea, where it functions as a high-affinity calcium sensor essential for synaptic vesicle exocytosis at the ribbon synapse (UniProt: O88430). It facilitates the rapid and sustained release of neurotransmitters required for the transmission of auditory information to the brain. Mutations in the OTOF gene result in autosomal recessive deafness type 9 (DFNB9), a condition characterized by profound sensorineural hearing loss or auditory neuropathy (NCBI Gene: 9381). Unlike many other forms of genetic deafness, DFNB9 is unique because the cochlear hair cells remain structurally intact for years, providing a window of opportunity for therapeutic intervention. Current clinical-stage treatments utilize gene replacement therapy, specifically dual adeno-associated virus (AAV) vectors, to deliver a functional copy of the OTOF gene directly into the cochlea (ClinicalTrials.gov: NCT05821959, NCT05572515). These therapies aim to restore the protein's function and re-establish hearing sensitivity in pediatric patients.

Other names

Fer-1-like protein 2DFNB9NSRD9Otoferlin

Gene replacement therapy utilizing dual adeno-associated virus (AAV) vectors to deliver a functional OTOF cDNA to inner hair cells, thereby restoring calcium-triggered glutamate release at the ribbon synapse (PubMed: 31010840).