OTOF

Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene.

Full Name

OTOF

Function

Key calcium ion sensor involved in the Ca2+-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes (By similarity).

Biological Process

Membrane fusionManual Assertion Based On ExperimentTAS:ProtInc
Plasma membrane organizationManual Assertion Based On ExperimentIBA:GO_Central
Sensory perception of soundManual Assertion Based On ExperimentTAS:ProtInc
Synaptic vesicle exocytosisISS:UniProtKB
Synaptic vesicle primingManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane
Basolateral cell membrane
Endoplasmic reticulum membrane
Golgi apparatus membrane
Cell junction, synapse, presynaptic cell membrane
Cell membrane
Detected at basolateral cell membrane with synaptic vesicles surrounding the ribbon and at the presynaptic plasma membrane in the inner hair cells (IHCs) at postnatal day 30 (P30). Colocalizes with GPR25 and RAB8B in inner hair cells.

Involvement in disease

Deafness, autosomal recessive, 9 (DFNB9):
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Auditory neuropathy, autosomal recessive, 1 (AUNB1):
A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. In some cases AUNB1 phenotype can be temperature sensitive.

Topology

Cytoplasmic: 1-1963
Helical: 1964-1984
Extracellular: 1985-1997