== Function == ADGRV1 (also known as GPR98 or VLGR1) encodes one of the largest G protein-coupled receptors in humans, with over 6000 amino acids. This receptor is a member of the adhesion GPCR family, characterized by a large extracellular N-terminal region containing multiple calx-beta domains and a GPS (GPCR proteolysis site) domain. ADGRV1 is expressed predominantly in the inner ear, retina, and central nervous system, where it plays critical roles in sensory perception and neuronal development. [@weston2004]
In the inner ear, ADGRV1 is essential for stereocilia organization and hair cell function, working alongside other proteins like USH2A (whirlin) in the ankle-link complex that connects stereocilia tips. In the brain, ADGRV1 is expressed in the cerebellum, [hippocampus](/brain-regions/hippocampus), and cerebral [cortex](/brain-regions/cortex), where it may function in synaptic organization and neuronal migration during development. [@bayne2005]
== Function == ADGRV1 (also known as GPR98 or VLGR1) encodes one of the largest G protein-coupled receptors in humans, with over 6000 amino acids. This receptor is a member of the adhesion GPCR family, characterized by a large extracellular N-terminal region containing multiple calx-beta domains and a GPS (GPCR proteolysis site) domain. ADGRV1 is expressed predominantly in the inner ear, retina, and central nervous system, where it plays critical roles in sensory perception and neuronal development. [@weston2004]
In the inner ear, ADGRV1 is essential for stereocilia organization and hair cell function, working alongside other proteins like USH2A (whirlin) in the ankle-link complex that connects stereocilia tips. In the brain, ADGRV1 is expressed in the cerebellum, [hippocampus](/brain-regions/hippocampus), and cerebral [cortex](/brain-regions/cortex), where it may function in synaptic organization and neuronal migration during development. [@bayne2005]
== Disease Associations == [@mcgee2006a] Mutations in ADGRV1 cause Usher syndrome type 2C (USH2C), a recessive disorder characterized by: [@michalski2017a]
Sensorineural Hearing Loss: Progressive hearing loss beginning in childhood
Retinitis Pigmentosa: Progressive retinal degeneration leading to tunnel vision and blindness
Vestibular Function: Typically normal vestibular function in USH2C
ADGRV1 mutations have also been associated with: [@ebermann2007a]
Febrile Seizures: Some variants may lower seizure threshold
Autism Spectrum Disorder: Rare variants reported in some ASD cohorts
Epilepsy: Specific variants linked to febrile and afebrile seizures
== Expression == [@weston2004a] ADGRV1 shows high expression in: [@nikkola2013]
Inner ear: Hair cells of the cochlea and vestibular organs
Retina: Photoreceptor cells and retinal pigment epithelium
[Bayebaa et al., Identification of ADGRV1 mutations causing Usher syndrome type 2C (2005)](https://doi.org/10.1016/j.ajhg.2005.07.004)
[McGee et al., The very large G-protein coupled receptor VLGR1: cell surface expression and localization in inner ear (2006)](https://doi.org/10.1002/cne.21050)
[Michalski et al., ADGRV1 and USH2A co-localize in retinal photoreceptor cells (2017)](https://doi.org/10.1016/j.exer.2017.07.012)
ADGRV1 (Adhesion G Protein-Coupled Receptor V1), also known as GPR98 or VLGR1, encodes the largest G protein-coupled receptor involved in synapse organization and auditory hair bundle development. ADGRV1 plays roles in synaptic transmission, calcium signaling, and neuronal excitability. Mutations in ADGRV1 cause Usher syndrome type IIA, characterized by hearing loss and retinitis pigmentosa. The gene has also been implicated in epilepsy and autism spectrum disorder.
Brain Atlas Resources
[Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
[Bayebaa et al., Identification of ADGRV1 mutations causing Usher syndrome type 2C (2005) (2005)](https://doi.org/10.1016/j.ajhg.2005.07.004)
[McGee et al., The very large G-protein coupled receptor VLGR1: cell surface expression and localization in inner ear (2006) (2006)](https://doi.org/10.1002/cne.21050)
[Michalski et al., ADGRV1 and USH2A co-localize in retinal photoreceptor cells (2017) (2017)](https://doi.org/10.1016/j.exer.2017.07.012)
[Ebermann et al., Genetic screening of USH2C patients reveals ADGRV1 mutations (2007) (2007)](https://doi.org/10.1007/s00439-007-0386-3)
[Weston et al., ADGRV1 (VLGR1) mutations in Usher syndrome type II (2004) (2004)](https://doi.org/10.1002/humu.9256)
[Bayne et al., Identification of ADGRV1 mutations causing Usher syndrome type 2C (2005) (2005)](https://doi.org/10.1016/j.ajhg.2005.07.004)
[McGee et al., The very large G-protein coupled receptor VLGR1: cell surface expression and localization in inner ear (2006) (2006)](https://doi.org/10.1002/cne.21050)
[Michalski et al., ADGRV1 and USH2A co-localize in retinal photoreceptor cells (2017) (2017)](https://doi.org/10.1016/j.exer.2017.07.012)
[Ebermann et al., GPR98 mutations cause Usher syndrome type 2 (2007) (2007)](https://doi.org/10.1016/j.ajhg.2007.09.014)
[Weston et al., ADGRV1 (VLGR1) mutations in Usher syndrome type II (2004) (2004)](https://doi.org/10.1002/humu.20017)
[Nikkola et al., Role of ADGRV1 in neuroligin binding and synaptogenesis (2013) (2013)](https://doi.org/10.1371/journal.pone.0053833)
[Beurg et al., Mechanoelectrical transduction by stereociliary bundles (2017) (2017)](https://doi.org/10.1016/j.tins.2017.04.002)
[Petit et al., Usher syndrome: Genetics and molecular basis (2021) (2021)](https://doi.org/10.1016/j.neuron.2021.01.016)