Defective SLC17A8 causes autosomal dominant deafness 25 (DFNA25)

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser
There are two classes of glutamate transporters; the excitatory amino acid transporters (EAATs) which depend on an electrochemical gradient of Na+ ions and vesicular glutamate transporters (VGLUTs) which are proton-dependent. Together, these transporters uptake and release glutamate to mediate this neurotransmitter's excitatory signal and are part of the glutamate-glutamine cycle. Three members of the SLC17A gene family (7, 6 and 8) encode VGLUTs 1-3 respectively. This uptake is thought to be coupled to the proton electrochemical gradient generated by the vacuolar type H+-ATPase. They are all expressed in the CNS in neuron-rich areas but SLC17A8 (VGLUT3) is also expressed on astrocytes and in the liver and kidney. Defects in SLC17A8 can cause autosomal dominant deafness 25 (DFNA25; MIM:605583), a form of non-syndromic sensorineural hearing loss. The cochlea expresses SLC17A8 and in mice which lack this transporter are congenitally deaf. Hearing loss is due to the lack of glutamate release by inner hair cells therefore a loss of synaptic transmission at the IHC-afferent nerve synapse. Successful restoration of hearing by gene replacement in mice could be a significant advance toward gene therapy of human deafness (Ruel et al. 2008, Akil et al. 2012).
Literature References
PubMed ID Title Journal Year
22841313 Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy

During, M, Burke, K, Lustig, LR, Edwards, RH, Seal, RP, Akil, O, Alemi, A, Wang, C

Neuron 2012
18674745 Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice

Smith, RJ, El Mestikawy, S, Bersot, T, Nouvian, R, Giros, B, Ruel, J, Emery, S, Delprat, B, Puel, JL, Moser, T, Sivakumaran, TA, Rebillard, G, Lenoir, M, Amilhon, B, Lesperance, MM, Eybalin, M, Van Rybroek, JM

Am. J. Hum. Genet. 2008
Name Identifier Synonyms
autosomal dominant nonsyndromic deafness DOID:0050564 autosomal dominant deafness
Cite Us!