Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Required for the arrangement of stereocilia in mature hair bundles (By similarity)

Cell projection, stereociliumCytoplasm, cytoskeleton

Deafness, autosomal recessive, 3

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.

Orphan G-protein coupled receptor involved in the regulation of hair cell orientation in mechanosensory organs of the inner ear. It is required to trigger a 180 degree reversal in hair cell orientation, creating a virtual line of polarity reversal (LPR) across which stereociliary bundles are arranged in opposite orientations

Cell membrane

Deafness, autosomal recessive, 121

A form of non-syndromic deafness characterized by congenital or prelingual onset of moderate sensorineural hearing loss. Sensorineural hearing loss 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.

Required to maintain microtubule bundles in inner ear supporting cells, affording them with mechanical stiffness to transmit sound energy through the cochlea

Cytoplasm, cytoskeleton, stress fiberMembrane

Deafness, autosomal recessive, 125

A form of non-syndromic deafness characterized by congenital sensorineural hearing loss. Sensorineural hearing loss 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.

Plasma membrane t-SNARE that mediates docking of transport vesicles (By similarity). Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane (By similarity). In neurons, recruited at neurite tips to membrane domains rich in the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) which promotes neurite tip surface expression of the dopamine transporter SLC6A3/DAT by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity). T

Cell membraneCell projection, neuron projectionCell projection, stereociliumCytoplasm, perinuclear region

Deafness, autosomal recessive, 123

A form of non-syndromic deafness characterized by bilateral, severe to profound sensorineural hearing loss with onset in the first decade of life. Sensorineural hearing loss 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.

mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Also regulates the splicing of CD44, CTNND1, ENAH, 3 transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of

Nucleus

Deafness, autosomal recessive, 109

A form of non-syndromic, sensorineural deafness characterized by bilateral, congenital, severe to profound 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. DFNB109 affected individuals additionally exhibit vestibular dysplasia, although they do not manifest problems with balance or movement.

Lipid transporter that specifically mediates export of sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and sphinganine-1-phosphate in the lymph, thereby playing a role in lymphocyte trafficking (PubMed:19074308, PubMed:21084291, PubMed:23180825). S1P is a bioactive signaling molecule that regulates many physiological processes important for the development and for the immune system (PubMed:19074308, PubMed:23180825). Regulates levels of S1P and the S1P gradient that exists between the

Cell membraneEndosome membrane

Deafness, autosomal recessive, 115

A form of non-syndromic deafness characterized by severe sensorineural hearing impairment in early childhood. 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.

Plays a key role to hearing function. Required for normal organization and maintenance of the stereocilia bundle and for mechano-electrical transduction

Cell projection, stereocilium membrane

Deafness, autosomal recessive, 117

A form of non-syndromic deafness characterized by prelingual, moderate-to-profound sensorineural hearing loss. Sensorineural hearing loss 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.

May be responsible for potassium buffering action of glial cells in the brain (By similarity). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it (PubMed:8995301). Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages (PubMed:8995301). The inward rectification is mainly d

MembraneBasolateral cell membrane

Seizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalance

A complex disorder characterized by generalized seizures with onset in infancy, delayed psychomotor development, ataxia, sensorineural hearing loss, hypokalemia, metabolic alkalosis, and hypomagnesemia.

Transcriptional activator required for the development of normal hearing, sense of balance and kidney function. Required for the expression of SLC26A4/PDS, JAG1 and COCH in a subset of epithelial cells and the development of the endolymphatic system in the inner ear. Also required for the expression of SLC4A1/AE1, SLC4A9/AE4, ATP6V1B1 and the differentiation of intercalated cells in the epithelium of distal renal tubules (By similarity)

Nucleus

Component of hair-cell stereocilia coat. Required for normal hearing

MembraneCell projection, stereocilium membrane

Deafness, autosomal recessive, 124

A form of non-syndromic deafness characterized by progressive sensorineural hearing loss with onset at birth. Sensorineural hearing loss 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.

In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links. Blocks inhibition of adenylate cyclase activity mediated by ADGRV1

Cell projection, ciliumNucleusCell projection, stereocilium

Deafness, autosomal recessive, 57

A form of non-syndromic, sensorineural deafness characterized by symmetric, bilateral hearing loss with onset in early childhood. Vestibular function is preserved. 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. DFNB57 severity ranges from moderate to severe.

Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) entry into hepatic cells

Cell junction, tight junctionCell membrane

Deafness, autosomal recessive, 116

A form of non-syndromic deafness characterized by slowly progressive, moderate to profound 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.

Multifunctional actin-bundling protein. Plays a major role in regulating the organization, dimension, dynamics and signaling capacities of the actin filament-rich microvilli in the mechanosensory and chemosensory cells (PubMed:29572253). Required for the assembly and stabilization of the stereociliary parallel actin bundles. Plays a crucial role in the formation and maintenance of inner ear hair cell stereocilia (By similarity). Involved in the elongation of actin in stereocilia (PubMed:29572253

Cytoplasm, cytoskeletonCell projection, stereociliumCell projection, microvillus

Deafness, autosomal recessive, 36, with or without vestibular involvement

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. DFNB36 is characterized by prelingual, profound hearing loss, and vestibular areflexia in some patients.

Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (By similarity). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR

Cytoplasm, cytosolCytoplasm, cytoskeletonCell projection, microvillus

Usher syndrome 1C

USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.

Required for hearing (By similarity). Plays a role in maintaining cochlear stereocilia bundles that are involved in sound detection (PubMed:24619944). Ensures the restriction of TPRN to the basal region of stereocilia in hair cells (By similarity)

Cell projection, stereocilium

Deafness, autosomal recessive, 101

A form of non-syndromic deafness characterized by bilateral, moderate to severe hearing loss. Vestibular function is unaffected.

Secreted

Deafness, autosomal recessive, 84B

A form of non-syndromic deafness characterized by congenital, non-progressive, sensorineural, symmetric hearing loss. Vestibular hypofunction is rarely observed.

Probable serine protease that plays a role in hearing. Acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival (By similarity). Activates ENaC (in vitro)

Endoplasmic reticulum membrane

Deafness, autosomal recessive, 8

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.

Pore-forming subunit of the mechanotransducer (MET) non-selective cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system (By similarity). The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, and aided by several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, and the tip-link PCDH15 (By similarity). MET channel is activated by tension in

Cell membrane

Deafness, autosomal dominant, 36

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. DFNA36 is a bilateral hearing loss, and begins at 5-10 years of age. It progresses to profound deafness within 10-15 years.

Cytoplasm

Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both bar

Cytoplasm, cell cortexCell projection, ruffle membraneCell projection, growth coneCell projection, stereociliumSynapse, synaptosome

Deafness, autosomal recessive, 102

A form of non-syndromic deafness characterized by profound hearing loss affecting all frequencies. Vestibular function is unaffected.

Required for normal inner ear hair cell function and hearing

Membrane

Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskel

Cytoplasm, cytosol

Deafness, autosomal recessive, 100

A form of non-syndromic, sensorineural deafness characterized by prelingual hearing impairment. 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.

Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane

Cell membraneCytoplasm, cytoskeletonCleavage furrowCell projection, microvillusCell projection, stereocilium

Deafness, autosomal recessive, 24

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.

Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. In the retina, plays an important role in the renewal of the outer photoreceptor disks. Plays an important role in the distribution and migration of retinal pigment epithelial (RPE) melanosomes and phagosomes, and in the regulation of opsin transport in retinal photore

CytoplasmCytoplasm, cell cortexCytoplasm, cytoskeletonSynapse

Usher syndrome 1B

USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.

Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining the proper organization of the stereocilia bundle of hair cells in the cochlea and the vestibule during late embryonic/early postnatal development. It is part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for norma

Cell membrane

Usher syndrome 1D

USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.

Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:17186462)

Cell membraneCell junction, tight junction

Deafness, autosomal recessive, 49

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.

ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:15829536, PubMed:17234811). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment (PubMed:15829536, PubMed:17234811). Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics. At parallel fiber to Purkinje neuron s

Cell membraneSynapseApical cell membraneBasolateral cell membrane

Dephosphorylates phosphatidylinositol phosphates, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 3,5-diphosphates, with preference for PIP3 (PubMed:23897475). Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring (PubMed:23897475). Has low tyrosine-protein phosphatase activity in vitro; however, the relevance of such activity in vivo is unclear (By similarity). Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regu

Cell projection, stereociliumApical cell membraneBasal cell membrane

Deafness, autosomal recessive, 84A

A form of non-syndromic deafness characterized by progressive, sensorineural hearing loss and vestibular dysfunction.

Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the asparagine amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis (PubMed:25385316). The reaction occurs in a two steps: asparagine is first activated by ATP to form Asn-AMP and then transferred to the acceptor end of tRNA(Asn) (Probable)

Mitochondrion matrixMitochondrion

Combined oxidative phosphorylation deficiency 24

An autosomal recessive mitochondrial disorder with wide phenotypic variability. Some patients have a milder form affecting only skeletal muscle, whereas others may have a more severe disorder, reminiscent of Alpers syndrome. Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter.

Involved in hearing. Required for normal function of hair cells in the inner ear (By similarity)

Cell projection, stereocilium

Deafness, autosomal recessive, 77

A form of non-syndromic deafness characterized by preserved low-frequency hearing, and a trend toward mild to moderate mid-frequency and high-frequency hearing loss during childhood and adolescence. Hearing loss progresses to become moderate to severe at mid and high frequencies during adulthood.

May act as an adhesion molecule

Apical cell membraneSecreted, extracellular space, extracellular matrix

Deafness, autosomal recessive, 22

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.

Mediates homophilic cell-cell adhesion

Membrane

Deafness, autosomal recessive, 111

A form of non-syndromic, sensorineural deafness characterized by early-onset, moderate to severe hearing loss with no vestibular involvement. 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.

Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (tTJs) (PubMed:23239027). Crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs. Mediates fatty acids and lipoproteins-stimulated CCK/cholecystokinin secretion in the small intestine. In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1 (By similar

Cell membraneCell junction, tight junctionCytoplasmCytoplasm, cytosol

Deafness, autosomal recessive, 42

A prelingual, non-progressive 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.

Involved in hearing and vision as member of the USH2 complex. Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear. Involved in the maintenance of the hair bundle ankle region, which connects stereocilia in cochlear hair cells of the inner ear. In retina photoreceptors, required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport

CytoplasmCell projection, stereociliumCell projection, growth conePhotoreceptor inner segmentSynapse

Deafness, autosomal recessive, 31

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.

One of the major non-collagenous components of the tectorial membrane (By similarity). The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals

Cell membraneSecreted, extracellular space, extracellular matrix

Deafness, autosomal dominant, 12

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.

Auxiliary subunit of the mechanotransducer (MET) non-specific cation channel complex located at the tips of the shorter stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system. The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, and aided by several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, and the tip-link PCDH15. Functionally couples PCDH15 to the transduction channel

Cell membrane

Deafness, autosomal recessive, 67

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.

Required for sound encoding at inner hair cells (IHCs) synapses, likely via inhibition of the inactivation of voltage-gated calcium channel of type 1.3 (Cav1.3) in the IHCs (PubMed:28183797). Required for the normal transfer of light signals through the retina (By similarity)

Cytoplasm, perinuclear regionCell membraneGolgi apparatus

Deafness, autosomal recessive, 93

A form of non-syndromic deafness characterized by stable, bilateral, symmetric, prelingual moderate to severe deafness. Hearing impairment is slightly more pronounced in the mid-frequencies, resulting in a distinctive shallow U-shaped audiogram.

Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis (By similarity). Acts as an auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells (By similarity). Essential for mechanoelectrical transduction (MET) currents in auditory hair cells and thereby required for hearing (By similarity). Regulates the function of hair cell mechanotransduction by controlling the distribution of transmembrane channel-like proteins TMC1 and T

CytoplasmCell projection, stereociliumPhotoreceptor inner segmentCell projection, cilium, photoreceptor outer segmentCell membrane, sarcolemma

Deafness, autosomal recessive, 48

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. DFNB48 patients have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies.

General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site

Nucleus

Deafness, autosomal recessive, 112

A form of non-syndromic, sensorineural deafness characterized by postlingual progressive hearing impairment. 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.

Regulates actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin and prevents its depolymerization (PubMed:18194665, PubMed:28438837). May also serve as a linker protein to recruit proteins required for F-actin formation and turnover (PubMed:18194665). Essential for correct mitotic progression (PubMed:22820163, PubMed:24692559) Plays a pivotal role in the formation of stereocilia rootlets Plays a pivotal role in the formation

NucleusCytoplasm, cytoskeleton, microtubule organizing center, centrosomeMidbodyChromosome, telomere

Deafness, autosomal recessive, 28

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.

Required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion

Deafness, autosomal recessive, 15

A form of non-syndromic sensorineural hearing loss with prelingual onset. 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.

Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization (PubMed:17150207, PubMed:23241886, PubMed:24687993, PubMed:24958875, PubMed:25588844, PubMed:27556504). Inhibits chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration (PubMed:23241886). Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion (By si

CytoplasmCytoplasm, cytoskeletonCell projection, filopodiumCell projection, stereociliumCell projection, stereocilium membraneApical cell membrane

Deafness, autosomal recessive, 104

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.

Peroxisome-associated protein required to protect auditory hair cells against noise-induced damage. Acts by regulating noise-induced peroxisome proliferation in auditory hair cells and neurons, and promoting autophagic degradation of damaged peroxisomes (pexophagy). Noise overexposure increases reactive oxygen species (ROS) levels, causing oxidative damage to auditory hair cells and resulting in hearing loss. PJVK acts as a ROS sensor that recruits the autophagy machinery to trigger pexophagy of

Peroxisome membraneCell projection, cilium

Deafness, autosomal recessive, 59

A form of sensorineural hearing impairment with absent or severely abnormal auditory brainstem response but normal otoacoustic emissions (auditory neuropathy or auditory dys-synchrony). 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.

Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P) (PubMed:10617617, PubMed:25274307). S1P is a bioactive lysophospholipid that elicits diverse physiological effects on most types of cells and tissues (PubMed:10617617). When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis (PubMed:10617617). Receptor for the chemokine-like protein FAM19A5 (PubMed:29453251). Mediates the inhibitory effect of FAM19A5 on vascular

Cell membrane

Deafness, autosomal recessive, 68

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.

Regulator of neurite outgrowth required for normal hearing and vision

Cell membrane

Deafness and myopia

An autosomal recessive disorder characterized by prelingual sensorineural hearing loss associated with high myopia.

One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell

Cell membraneCell junction, gap junction

Erythrokeratodermia variabilis et progressiva 1

A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.

Essential to the formation of horizontal top connectors between outer hair cell stereocilia

Cell surfaceCell projection, kinociliumCell projection, stereocilium

Deafness, autosomal recessive, 16

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.

Acts as a GTPase-activating protein (GAP) for ARL2 with low specific activity

Cell projection, stereociliumCell projection, kinociliumCytoplasm, cytoskeleton

Deafness, autosomal recessive, 88

A form of non-syndromic deafness characterized by prelingual onset of severe to profound mixed conductive and sensorineural hearing loss.

Auxiliary subunit of the mechanotransducer (MET) non-specific cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system. The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, and aided by several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, and the tip-link PCDH15. May contribute to the formation of the pore

Membrane

Deafness, autosomal recessive, 6

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.

One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell

Cell membraneCell junction, gap junction

Ectodermal dysplasia 2, Clouston type

A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD2 is an autosomal dominant condition characterized by atrichosis, nail hypoplasia and deformities, hyperpigmentation of the skin, normal teeth, normal sweat and sebaceous gland function. Palmoplantar hyperkeratosis is a frequent feature. Hearing impairment has been detected in few cases.

Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity

Cell junction, tight junctionCell membrane

Deafness, autosomal recessive, 29

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.

Dual-specificity phosphatase. Required for centrosome separation and productive cytokinesis during cell division. Dephosphorylates SIRT2 around early anaphase. May dephosphorylate the APC subunit FZR1/CDH1, thereby promoting APC-FZR1 dependent degradation of mitotic cyclins and subsequent exit from mitosis. Required for normal hearing (PubMed:29293958)

NucleusCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, spindle poleCytoplasm, cytoskeleton, spindleCell projection, kinociliumCell projection, stereocilium

Deafness, autosomal recessive, 32, with or without immotile sperm

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. DFNB32 is characterized by prelingual, progressive, moderate to profound sensorineural deafness. Some affected men are infertile.

Glycoprotein specific to acellular membranes of the inner ear. May be required for the anchoring of the otoconial membranes and cupulae to the underlying neuroepithelia in the vestibule. May be involved in the organization and/or stabilization of the fibrillar network that compose the tectorial membrane in the cochlea. May play a role in mechanotransduction processes (By similarity)

Apical cell membraneSecreted, extracellular space

Deafness, autosomal recessive, 18B

A form of non-syndromic deafness characterized by a moderate hearing impairment, which can be associated with vestibular dysfunction, and a flat to shallow 'U' or slightly downsloping shaped audiograms.

Myosins are actin-based motor molecules with ATPase activity (By similarity). Unconventional myosins serve in intracellular movements (By similarity). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (PubMed:10519557). Has slow rate of actin-activated ADP release due to weak ATP binding (By similarity). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (By similarity). Required for the stru

Golgi apparatus, trans-Golgi network membraneGolgi apparatusNucleusCytoplasm, perinuclear regionMembrane, clathrin-coated pitCytoplasmic vesicle, clathrin-coated vesicleCell projection, filopodiumCell projection, ruffle membraneCell projection, microvillusCytoplasm, cytosolCytoplasmic vesicle, autophagosomeEndosomeCytoplasmic vesicle, clathrin-coated vesicle membrane

Deafness, autosomal dominant, 22

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. DFNA22 is progressive and postlingual, with onset during childhood. By the age of approximately 50 years, affected individuals invariably have profound sensorineural deafness.

Key calcium ion sensor involved in the Ca(2+)-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)

Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membraneBasolateral cell membraneEndoplasmic reticulum membraneGolgi apparatus membranePresynaptic cell membraneCell membraneGolgi apparatus, trans-Golgi network

Deafness, autosomal recessive, 9

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.

In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor (By similarity). Can insert into membranes and form non-selective ion channels almost equally permeable to Na(+), K(+) and Cl(-) (PubMed:15184393, PubMed:18028448). Required for normal hearing (PubMed:24781754). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti (By similarity). May play a role in the regulatio

Cytoplasm, cytoskeletonCytoplasm, cell cortexMembraneApical cell membraneCytoplasmMitochondrionCell projection, stereociliumGolgi apparatusCytoplasm, cytoskeleton, microtubule organizing center, centrosome

Deafness, autosomal recessive, 103

A form of sensorineural deafness with onset in early childhood. Hearing impairment progresses from mild to severe or even profound before the second decade, and is accompanied by vestibular areflexia.

Couples signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. Plays a role in the inner ear and in hearing (PubMed:30610177)

MembraneSynapse

Deafness, autosomal recessive, 114

A form of non-syndromic deafness characterized by congenital profound 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.

Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing

Cytoplasm, cytoskeletonCytoplasmCell projection, filopodium tipCell projection, stereocilium

Deafness, autosomal recessive, 30

A form of non-syndromic deafness characterized by bilateral progressive hearing loss, which first affects the high frequencies. Hearing loss begins in the second decade, and by age 50 is severe in high and middle frequencies and moderate at low frequencies.

Essential for hearing (By similarity). Required for maintenance of stereocilia on both inner and outer hair cells (By similarity). Necessary for the integrity of the stereociliary rootlet (By similarity). May act as an actin cytoskeleton regulator involved in the regulation of actin dynamics at the pointed end in hair cells (By similarity). Forms rings at the base of stereocilia and binds actin filaments in the stereocilia which may stabilize the stereocilia (By similarity). Acts as a strong inh

Cell projection, stereociliumCell projection, microvillusNucleus, nucleoplasmCytoplasm

Deafness, autosomal recessive, 79

A form of non-syndromic deafness characterized by progressive and severe sensorineural hearing loss. There are no symptoms of vestibular dysfunction.

Calcium-dependent cell-adhesion protein. Essential for maintenance of normal retinal and cochlear function

Cell membraneSecreted

Usher syndrome 1F

USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.

Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane

Secreted

Deafness, autosomal dominant, 4B

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.

Voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ (By similarity). Converts changes in the transmembrane electric potential into mechanical displacements resulting in the coupling of its expansion to movement of a charged voltage sensor across the lipid membrane (By similarity). The nature of the voltage sensor is not completely clear, and two models compete. In the first model, acts as an incomplet

Lateral cell membrane

Deafness, autosomal recessive, 61

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.

Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Involved in morula development

NucleusCytoplasmChromosome

Deafness, autosomal recessive, 35

A form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss.

RNA-binding protein implicated in numerous RNA metabolic processes (PubMed:29967381, PubMed:39019044). Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction (PubMed:29967381, PubMed:39019044). Mitochondrial intermembrane factor with RNA-processing exoribonulease activity (PubMed:29967381, PubMed:39019044). Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in

CytoplasmMitochondrion matrixMitochondrion intermembrane space

Combined oxidative phosphorylation deficiency 13

A mitochondrial disorder characterized by early onset severe encephalomyopathy, dystonia, choreoathetosis, bucofacial dyskinesias and combined mitochondrial respiratory chain deficiency. Nerve conductions velocities are decreased. Levels of plasma and cerebrospinal fluid lactate are increased.

May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils

Secreted, extracellular space, extracellular matrix

Otospondylomegaepiphyseal dysplasia, autosomal dominant

An autosomal dominant form of otospondylomegaepiphyseal dysplasia, a disorder characterized by sensorineural deafness, enlarged epiphyses, mild platyspondyly, and disproportionate shortness of the limbs. Total body length is normal. Typical facial features are mid-face hypoplasia, short upturned nose and depressed nasal bridge. Most patients have Pierre Robin sequence including an opening in the roof of the mouth (cleft palate) and a small lower jaw (micrognathia). Ocular symptoms are absent. Some patients have early-onset osteoarthritis.

Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization (PubMed:15167892, PubMed:20977675). Activates MAPK signaling following TMPRSS13 cleavage and activation (PubMed:20977675)

Deafness, autosomal recessive, 39

A form of profound prelingual 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.

Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels (By similarity). May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity)

MembraneCell membraneCytoplasmMembrane raft

Deafness, autosomal recessive, 44

A form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies.

As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (By similarity). Behaves as a kinesin cargo, providing a functional binding site for kinesin-1 at the nuclear envelope. Hence may contribute to t

Nucleus outer membrane

Deafness, autosomal recessive, 76

A form of non-syndromic sensorineural deafness, a disorder resulting 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. DFNB76 affected individuals have onset of progressive high frequency hearing impairment between birth and 6 years of age. The hearing loss is severe at high frequencies by adulthood.

Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing

Endoplasmic reticulumMitochondrion

Deafness, autosomal recessive, 74

A form of non-syndromic sensorineural deafness characterized by prelingual, bilateral, profound 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.

Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:18029264, PubMed:18272479, PubMed:9278442). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby media

Cytoplasm, cytosolCytoplasmNucleusCell membraneSecretedMitochondrion

Charcot-Marie-Tooth disease, recessive intermediate B

A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.

Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton. In the cochlea, is required for stereocilia maintenance in adult hair cells (By similarity)

CytoplasmCell projection, stereocilium

Deafness, autosomal recessive, 106

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.

Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350). Via IGFBP5 ligand, forms a complex with ERBB2 to enhance CREB oncogenic signaling (PubMed:36949068)

MembraneCell projection, axon

Deafness, autosomal recessive, 108

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.

Binds cholesterol and may regulate the distribution and homeostasis of cholesterol in hair cells (PubMed:36317962). May play a role in angiogenesis (PubMed:35727972)

Lysosome membraneEndoplasmic reticulum membrane

Deafness, autosomal recessive, 120

A form of non-syndromic deafness characterized by congenital or prelingual onset of severe to profound sensorineural hearing loss. Sensorineural hearing loss 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.

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1,

MembraneSecreted

Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between neighboring cells (By similarity). Forms homotypic and heterotypic channels gated by transjunctional voltage (By similarity). May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph (Probabl

Cell membraneCell junction, gap junctionEndoplasmic reticulumCell junction

Oculodentodigital dysplasia

A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances.

Sodium-independent transporter of chloride and iodide (PubMed:10192399, PubMed:11932316, PubMed:12107249, PubMed:16684826, PubMed:24051746). Mediates electroneutral chloride-bicarbonate, chloride-iodide and chloride-formate exchange with 1:1 stoichiometry (PubMed:10644529, PubMed:15155570, PubMed:24051746, PubMed:35601831). Mediates electroneutral iodide-bicarbonate exchange (By similarity)

Cell membraneApical cell membrane

Pendred syndrome

An autosomal recessive disorder characterized by congenital sensorineural hearing loss in association with thyroid goiter. The disorder may account for up to 10% of the cases of hereditary deafness. The deafness is most often associated with a Mondini cochlear defect. Deafness occurs early, starting at birth or during the first years of life. It is bilateral, sometimes asymmetrical, fluctuant and often progressive. Thyroid perturbations, such as thyroid goiter and/or hypothyroidism appear most commonly during adolescence, but they can be congenital or appear later.

May act as a GTPase-activating protein for Rab family protein(s) (PubMed:20727515, PubMed:20797691). Involved in neuronal projections development, probably through a negative modulation of ARF6 function (PubMed:20727515). Involved in the regulation of synaptic vesicle trafficking (PubMed:31257402)

Cell membraneCytoplasmCytoplasmic vesicle membranePresynapse

Familial infantile myoclonic epilepsy

A subtype of idiopathic epilepsy starting in early infancy and manifesting as myoclonic seizures, febrile convulsions, and tonic-clonic seizures.

ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase ac

CytoplasmCytoplasm, cytoskeleton, spindleNucleus

Deafness, autosomal recessive, 119

A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss. Sensorineural hearing loss 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.

Acts as a transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation (PubMed:16772533). In presence of estrogen, binds to ESR1-responsive promoters (PubMed:16772533). Synergizes with YAP1 to enhance PGR activity (PubMed:16772533). Modulates expression of post-synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR (By similarity)

CytoplasmNucleus

Deafness, autosomal recessive, 107

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.

Regulatory subunit of anion-selective CLCNKA:BSND and CLCNKB:BSND heteromeric channels involved in basolateral chloride conductance along the nephron to achieve urine concentration and maintain systemic acid-base homeostasis, and in the stria vascularis of the inner ear to establish the endocochlear potential necessary for normal hearing (PubMed:11734858, PubMed:12111250, PubMed:12574213, PubMed:16849430, PubMed:18776122, PubMed:19646679, PubMed:20538786, PubMed:26013830). Most likely acts as a

Basolateral cell membrane

Bartter syndrome 4A, neonatal, with sensorineural deafness

A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS4A is associated with sensorineural deafness.

May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood (By similarity). Inhibitor of cathepsin G, kallikrein-8 and thrombin. May play an important role in the inner ear in the protection against leakage of lysosomal content during stress and loss of this protection results in cell death and sensorineural hearing loss

Cytoplasm

Deafness, autosomal recessive, 91

A form of non-syndromic deafness characterized by progressive and age-dependent sensorineural hearing loss. Vestibular function is normal.

Protein that plays a role in the inhibition of canonical Wnt signaling pathway (PubMed:25557784). May be involved in neuronal migration during development of the cerebral neocortex (By similarity). Involved in the control of ciliogenesis and ciliary length (PubMed:25601850, PubMed:27319779)

Cell projection, ciliumCytoplasm, cytoskeleton, cilium axonemeCell projection, kinociliumCytoplasm, cytoskeleton

Dyslexia 2

A relatively common, complex cognitive disorder characterized by an impairment of reading performance despite adequate motivational, educational and intellectual opportunities. It is a multifactorial trait, with evidence for familial clustering and heritability.

Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202, PubMed:21816348). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). Plays a role in metaphase spindle orientation (PubMed:22327364). Also plays an important role in asymmetric cell divisions (PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and

CytoplasmCytoplasm, cell cortexCytoplasm, cytoskeleton, spindle poleLateral cell membrane

Chudley-McCullough syndrome

An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal.

Structural component of gap junctions (PubMed:16849369, PubMed:17551008, PubMed:19340074, PubMed:19384972, PubMed:21094651, PubMed:26753910). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (PubMed:17551008, PubMed:19340074, PubMed:21094651, PubMed:26753910). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:16849369, PubM

Cell membraneCell junction, gap junction

Deafness, autosomal recessive, 1A

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.

May play a role in actin filament architecture in developing stereocilia of sensory cells

Cell projection, stereociliumCell projection, microvillusCell projection, kinocilium

Deafness, autosomal recessive, 25

A form of non-syndromic sensorineural deafness characterized by moderate to severe or profound hearing loss which is progressive in some individuals but not in others. Speech development is impaired in some but not all affected individuals, and vestibular dysfunction is observed in some affected individuals. 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.