AUDITORY MECHANOTRANSDUCTION PATHWAY (PW:0001503)
Description
The auditory system has exquisitely intricate mechanisms that convert mechanical stimuli - mechanotransduction, intro electrical signals that are processed by the brain and account for the perception of sound, gravity and movement. The inner ear - a fluid-filled organ, contains the shell-shaped cochlea and the vestibule responsible for sound and for gravitation and movement mechanotransduction, respectively. Within the cochlea, the organ of Corti (OC) contains the hair cells - specialized sensory cells that carry out the auditory mechanotransduction pathway. In the mammalian OC, the hair cells are arranged in three rows of outer hair cells (OHC) and one of inner hair cell (IHC). Hair cells have protruding hair bundles and each hair bundle contains actin-filled stereocilia. Apically, the hair cells are covered by the tectorial membrane; basally, hair cells and various associated non-sensory cells referred to as supporting cells, sit on the basilar membrane. Oscillations in air pressure generated by sound waves are converted into fluid pressure that induce vibrations into the basilar membrane leading to deflections of the hair bundles, opening of mechanotransducer channels and cell depolarization. OHC serve as amplifiers while IHC transduce the auditory input. Specialized bipolar neurons known as spiral ganglion neuron (SGN) type I and II are the afferent connections of IHC (90-95% of SGN population) and OHC (remaining 5-10%), respectively; in turn, connecting to the brain. Specialized ribbon synapses are located at the pre-synaptic active zone of IHC and tethered by synaptic vesicles; upon stimulation they release glutamate. Slc17a8 known as Vglut3 is the IHC glutamate transporter. The molecular mechanisms of ribbon synapse function are not fully characterized yet. OHC are innervated by olivocochlear efferents originating from the superior olivary complex in the brainstem with an inhibitory effect. Each sterocilium in the hair bundle is connected to the next taller sterocilium neighbor via the tip link. The electron-dense areas at the insertion points of the tip link into the stereocilia are referred to as the lower tip-link density (LTLD) and upper tip-link density (UTLD), respectively. An elusive mechanotransduction (MET) channel - a non-selective cation channel with preference for calcium (Ca2+) and also potassium (K+) oscillates between open and closed states in the absence of stimuli; the molecular identity of the channel continues to be a conundrum. Stimuli that deflect the hair bundles of hair cells towards the tallest sterocilium result in the channel being open longer; if the tilt is towards the shortest, the channel closes. There are probably ~2 channels per stereocilium and they are located at the base of the tip link. The tip links consist of parallel cis-homodimers of cadherin 23 (Cdh23) interacting in trans with parallel protocadherin 15 (Pcdh15) cis-homodimers. Classical cadherins are characterized by the presence of five extracellular cadherin (EC) repeats; Cdh23 and Pcdh15 differ from the classical cadherins in that they contain 27 and 11 EC repeats, respectively. Adapters and myosin motors are associated with UTLD, LTLD and the stereocilium. The adapter Ush1c known as harmonin, is found in UTLD; it interacts with Myo7a and in vitro, with both Cdh23 and Pcdh15. Also, at UTLD is Myo1c which binds phosphatidylinositol 4,5-bisphosphate (PIP2) and in vitro, interacts with Cdh23. At LTLD there are Myo15a and the adapter Dfnb31, known as whirlin whose domain structure is similar to Ush1c/harmonin. Also at LTLD is Myo3a which interacts with the actin crosslinker espin (Espn). Ush1g known as Sans appears to reside at both LTLD and UTLD; structural studies indicate that Ush1c/harmonin and Ush1g/Sans can interact and the latter can also interact with Myo7a. The core of sterocilia has cross-linked and bundled actin filaments with a 2:1 ratio of gamma Actg1 to beta Actb, that are cross-linked by Espn, plastin 1 (Pls1) and t-Plastin (Pls3). At the base of stereocilia are Gpr98 known as Vlgr1 and Ush2a known as usherin. Myo6 is found in the cuticular plate to which the stereocilia are anchored; it interacts with otoferlin, a synaptic vesicle protein. Ptprq is also at the base of the stereocilium. How the tip links open the channels is not clear but models have been proposed and there are also models for the adaptation to mechanical stimuli that occurs on fast and slow timescale. More detailed functional characterization of proteins presented here and of others postulated to be implicated, is still to be delineated. Many of the proteins associated with the auditory mechanotransduction system have been implicated in hearing loss either non-syndromic or syndromic as in the case of Usher which also involves the blindness phenotype of retinitis pigmentosa (RP).
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Pathway Diagram:
Genes in Pathway:
G
Actb
actin, beta
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr12:16,776,664...16,779,634
Ensembl chr12:16,776,661...16,780,242
G
Actg1
actin, gamma 1
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr10:106,118,106...106,120,951
Ensembl chr10:106,118,108...106,120,951
G
Adgrv1
adhesion G protein-coupled receptor V1
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr 2:13,067,149...13,647,407
Ensembl chr 2:13,067,150...13,647,372
G
Cdh23
cadherin-related 23
ISO
RGD
PMID:19804752 PMID:22177415
RGD:8547667 , RGD:8547671
NCBI chr20:28,783,124...29,165,624
Ensembl chr20:28,783,564...29,165,332
G
Espn
espin
ISO
RGD
PMID:19804752 PMID:20624897
RGD:8547667 , RGD:8547669
NCBI chr 5:167,909,271...167,943,168
Ensembl chr 5:167,909,271...167,942,984
G
Myo15a
myosin XVA
ISO
RGD
PMID:19804752
RGD:8547667
NCBI chr10:45,776,907...45,835,473
Ensembl chr10:45,776,907...45,835,473
G
Myo1c
myosin 1C
ISO
RGD
PMID:19804752
RGD:8547667
NCBI chr10:60,996,642...61,019,022
Ensembl chr10:60,996,638...61,019,022
G
Myo3a
myosin IIIA
ISO
RGD
PMID:19804752
RGD:8547667
NCBI chr17:89,451,567...89,667,654
Ensembl chr17:89,451,567...89,667,654
G
Myo6
myosin VI
ISO
RGD
PMID:20624897 PMID:22715884
RGD:8547669 , RGD:8547672
NCBI chr 8:89,967,351...90,122,219
Ensembl chr 8:89,967,377...90,122,215
G
Myo7a
myosin VIIA
ISO
RGD
PMID:19804752 PMID:22177415
RGD:8547667 , RGD:8547671
NCBI chr 1:161,755,110...161,825,397
Ensembl chr 1:161,755,110...161,825,365
G
Otof
otoferlin
ISO
RGD
PMID:22715884
RGD:8547672
NCBI chr 6:31,647,869...31,744,476
Ensembl chr 6:31,647,914...31,744,476
G
Pcdh15
protocadherin related 15
ISO
RGD
PMID:19804752 PMID:22177415
RGD:8547667 , RGD:8547671
NCBI chr20:13,996,383...15,495,206
Ensembl chr20:13,999,116...15,493,958
G
Pls1
plastin 1
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr 8:105,196,312...105,306,252
Ensembl chr 8:105,197,455...105,292,447
G
Pls3
plastin 3
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr X:116,401,247...116,495,898
Ensembl chr X:116,401,293...116,495,893
G
Ptprq
protein tyrosine phosphatase, receptor type, Q
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr 7:44,720,916...44,903,291
Ensembl chr 7:44,720,916...44,903,291
G
Slc17a8
solute carrier family 17 member 8
ISO
RGD
PMID:22715884
RGD:8547672
NCBI chr 7:25,881,557...25,936,837
Ensembl chr 7:25,881,557...25,935,410
G
Ush1c
USH1 protein network component harmonin
ISO
RGD
PMID:19804752 PMID:22177415
RGD:8547667 , RGD:8547671
NCBI chr 1:105,831,719...105,880,082
Ensembl chr 1:105,831,723...105,880,082
G
Ush1g
USH1 protein network component sans
ISO
RGD
PMID:22177415
RGD:8547671
NCBI chr10:101,055,923...101,062,753
Ensembl chr10:101,057,208...101,062,564
G
Ush2a
usherin
ISO
RGD
PMID:20624897
RGD:8547669
NCBI chr13:102,368,783...103,035,230
Ensembl chr13:102,368,783...103,035,217
G
Whrn
whirlin
ISO
RGD
PMID:19804752
RGD:8547667
NCBI chr 5:81,843,820...81,933,400
Ensembl chr 5:81,843,820...81,927,381
Pathway Gene Annotations
Disease Annotations Associated with Genes in the auditory mechanotransduction pathway
Actb Aminoacylase 1 Deficiency , Animal Mammary Neoplasms , Baraitser-Winter syndrome , Baraitser-Winter syndrome 1 , Becker Nevus Syndrome , carcinoma , Chemical and Drug Induced Liver Injury , coloboma , CONGENITAL SMOOTH MUSCLE HAMARTOMA, WITH OR WITHOUT HEMIHYPERTROPHY , Craniofacial Abnormalities , Dwarfism , dysostosis , dystonia , Esophageal Neoplasms , Experimental Mammary Neoplasms , Febrile Seizures , genetic disease , hand, foot and mouth disease , hepatocellular carcinoma , Hypoxia , intellectual disability , Juvenile-Onset Dystonia , Lung Neoplasms , metabolic dysfunction-associated steatotic liver disease , Myocardial Ischemia , Neoplasm Invasiveness , Nervous System Malformations , Neurodevelopmental Disorders , osteoarthritis , sensorineural hearing loss , smooth muscle hamartoma , temporal lobe epilepsy , thrombocytopenia , Thrombocytopenia 8 Actg1 Acute Coronary Syndrome , Animal Mammary Neoplasms , autosomal dominant nonsyndromic deafness 20 , Baraitser-Winter syndrome , Baraitser-Winter syndrome 1 , Baraitser-Winter syndrome 2 , CAKUT , carcinoma , coloboma , Craniofacial Abnormalities , Experimental Mammary Neoplasms , genetic disease , Hearing Loss , intellectual disability , lissencephaly , microcephaly , Neoplastic Cell Transformation , Nervous System Malformations , nonsyndromic deafness , osteoporosis , Presbycusis Adgrv1 arteriovenous malformations of the brain , autosomal recessive nonsyndromic deafness , beta-mannosidosis , familial adenomatous polyposis 1 , familial febrile seizures 1 , familial febrile seizures 4 , fundus dystrophy , genetic disease , Hearing Loss , Hereditary Neoplastic Syndromes , Idiopathic Generalized Epilepsy , Meniere's disease , Neurodevelopmental Disorders , optic atrophy , retinitis pigmentosa , Usher syndrome , Usher syndrome type 1 , Usher syndrome type 2 , Usher syndrome type 2A , Usher Syndrome Type 2B , Usher syndrome type 2C Cdh23 atypical Gaucher's disease due to saposin C deficiency , Atypical Krabbe Disease due to Saposin A Deficiency , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 12 , beta-mannosidosis , combined saposin deficiency , Deafness , fundus dystrophy , genetic disease , Hearing Loss , Hearing Loss, Noise-Induced , Hereditary Neoplastic Syndromes , Krabbe disease , Meniere's disease , metachromatic leukodystrophy , Metachromatic Leukodystrophy due to Saposin B Deficiency , Neurodevelopmental Disorders , nonsyndromic deafness , Nonsyndromic Sensorineural Hearing Loss , optic atrophy , pituitary adenoma 5 , pneumoconiosis , Presbycusis , retinal disease , retinitis pigmentosa , retinitis pigmentosa-deafness syndrome , sensorineural hearing loss , Stickler syndrome , Usher syndrome , Usher syndrome type 1 , Usher Syndrome Type 1B , Usher syndrome type 1D , Usher syndrome type 2 , Usher syndrome type 2A , Usher Syndrome, Type ID/F Espn autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 36 , chromosome 1p36 deletion syndrome , Deafness , fundus dystrophy , genetic disease , Hearing Loss , Neurodevelopmental Disorders , optic atrophy , sensorineural hearing loss , Usher syndrome type 1 , Usher Syndrome Type 1M , vestibular disease Myo15a Alport syndrome , autistic disorder , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 3 , autosomal recessive nonsyndromic deafness 9 , Birt-Hogg-Dube syndrome , blindness , common variable immunodeficiency 2 , Deafness, with Smith-Magenis Syndrome , genetic disease , Hearing Loss , Joubert syndrome , nonsyndromic deafness , Potocki-Lupski syndrome , sensorineural hearing loss Myo1c atrial fibrillation , Experimental Liver Cirrhosis , Meniere's disease , Miller-Dieker lissencephaly syndrome , syndromic microphthalmia 5 Myo3a autosomal dominant nonsyndromic deafness 30 , autosomal dominant nonsyndromic deafness 90 , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 30 , Bilateral Hearing Loss , genetic disease , Hearing Loss , nonsyndromic deafness , Nonsyndromic Sensorineural Hearing Loss , sensorineural hearing loss Myo6 autosomal dominant nonsyndromic deafness , autosomal dominant nonsyndromic deafness 22 , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 37 , COVID-19 , essential tremor , genetic disease , Hearing Loss , hypertension , junctional epidermolysis bullosa with pyloric atresia , male infertility , Meniere's disease , nonsyndromic deafness , Nonsyndromic Sensorineural Hearing Loss , ovarian cancer , prostate cancer , Sensorineural Deafness with Hypertrophic Cardiomyopathy , sensorineural hearing loss , substance-related disorder , Ullrich congenital muscular dystrophy 2 , Waardenburg syndrome Myo7a Auditory Neuropathy , autosomal dominant nonsyndromic deafness 11 , autosomal dominant nonsyndromic deafness 80 , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 2 , autosomal recessive nonsyndromic deafness 7 , Cohen syndrome , congenital nystagmus , COVID-19 , Cutis Verticis Gyrata, Retinitis Pigmentosa, and Sensorineural Deafness , Deafness , fundus dystrophy , genetic disease , Hearing Loss , hereditary breast ovarian cancer syndrome , intellectual disability , Leber congenital amaurosis , melanoma , Meniere's disease , nonsyndromic deafness , Nonsyndromic Sensorineural Hearing Loss , optic atrophy , Pendred syndrome , retinitis pigmentosa , retinitis pigmentosa-deafness syndrome , sensorineural hearing loss , Usher syndrome , Usher syndrome type 1 , Usher Syndrome Type 1B , Usher syndrome type 2 , vestibular disease Otof Arthrogryposis and Ectodermal Dysplasia , Auditory Neuropathy , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 3 , autosomal recessive nonsyndromic deafness 9 , COVID-19 , Deafness , genetic disease , Hearing Loss , hypothyroidism , mitochondrial trifunctional protein deficiency , nonsyndromic deafness , Pendred syndrome , sensorineural hearing loss , Tatton-Brown-Rahman syndrome Pcdh15 autistic disorder , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 23 , cochlear disease , Deafness , fundus dystrophy , genetic disease , Hearing Loss , Hirschsprung's disease , Meniere's disease , nonsyndromic deafness , Nonsyndromic Sensorineural Hearing Loss , optic atrophy , retinitis pigmentosa , retinitis pigmentosa-deafness syndrome , schizophrenia , substance-related disorder , Usher syndrome , Usher syndrome type 1 , Usher Syndrome Type 1B , Usher syndrome type 1D , Usher syndrome type 1F , Usher syndrome type 1G , Usher Syndrome, Type ID/F Pls1 autosomal dominant nonsyndromic deafness , autosomal dominant nonsyndromic deafness 76 , genetic disease , Hearing Loss , Liver Neoplasms , sensorineural hearing loss Pls3 Anterior Diaphragmatic Hernia , autistic disorder , autosomal hemophilia A , Chemical and Drug Induced Liver Injury , congenital diaphragmatic hernia , factor VIII deficiency , genetic disease , osteoarthritis , osteogenesis imperfecta , osteoporosis , Postmenopausal Osteoporosis , syndromic X-linked intellectual disability Lubs type Ptprq autosomal dominant centronuclear myopathy , autosomal dominant nonsyndromic deafness 73 , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 84A , congenital structural myopathy , Deafness , genetic disease , Hearing Loss , sensorineural hearing loss Slc17a8 autosomal dominant nonsyndromic deafness 25 , autosomal recessive nonsyndromic deafness 9 , cochlear disease , genetic disease , Hyperalgesia , Nonsyndromic Sensorineural Hearing Loss , Parkinsonism , sciatic neuropathy , transient cerebral ischemia , trichinosis Ush1c autosomal recessive nonsyndromic deafness , Autosomal Recessive Nonsyndromic Deafness 18 , autosomal recessive nonsyndromic deafness 18A , fundus dystrophy , genetic disease , Hearing Loss , intellectual disability , Meniere's disease , optic atrophy , progressive myoclonus epilepsy 7 , retinitis pigmentosa , retinitis pigmentosa-deafness syndrome , sensorineural hearing loss , Usher syndrome , Usher syndrome type 1 , Usher Syndrome Type 1B , Usher syndrome type 1C , Usher syndrome type 2 Ush1g autosomal recessive nonsyndromic deafness , Autosomal Recessive Nonsyndromic Deafness 18 , autosomal recessive nonsyndromic deafness 18A , Deafness , fundus dystrophy , genetic disease , Hearing Loss , Nonsyndromic Sensorineural Hearing Loss , optic atrophy , retinitis pigmentosa , retinitis pigmentosa-deafness syndrome , Usher syndrome , Usher syndrome type 1 , Usher syndrome type 1G Ush2a autism spectrum disorder , autosomal recessive nonsyndromic deafness , Bardet-Biedl syndrome , blindness , cone-rod dystrophy , cone-rod dystrophy 3 , congenital stationary night blindness , Deafness , fundus dystrophy , gastrointestinal stromal tumor , genetic disease , Hearing Loss , Joubert syndrome , Leber congenital amaurosis , Loeys-Dietz syndrome 4 , macular degeneration , nonsyndromic deafness , optic atrophy , parathyroid carcinoma , prostate cancer , Pulmonary Surfactant Metabolism Dysfunction 2 , retinal degeneration , retinitis pigmentosa , retinitis pigmentosa 39 , retinitis pigmentosa-deafness syndrome , sensorineural hearing loss , Usher syndrome , Usher syndrome type 1 , Usher syndrome type 2 , Usher syndrome type 2A , Usher syndrome type 3A , Vision Disorders Whrn Aland Island eye disease , autosomal recessive nonsyndromic deafness , autosomal recessive nonsyndromic deafness 31 , Deafness , fundus dystrophy , genetic disease , Hearing Loss , optic atrophy , retinitis pigmentosa-deafness syndrome , sensorineural hearing loss , Usher syndrome , Usher syndrome type 2D
Acute Coronary Syndrome Actg1 Aland Island eye disease Whrn Alport syndrome Myo15a Aminoacylase 1 Deficiency Actb Animal Mammary Neoplasms Actb , Actg1 Anterior Diaphragmatic Hernia Pls3 arteriovenous malformations of the brain Adgrv1 Arthrogryposis and Ectodermal Dysplasia Otof atrial fibrillation Myo1c atypical Gaucher's disease due to saposin C deficiency Cdh23 Atypical Krabbe Disease due to Saposin A Deficiency Cdh23 Auditory Neuropathy Myo7a , Otof autism spectrum disorder Ush2a autistic disorder Myo15a , Pcdh15 , Pls3 autosomal dominant centronuclear myopathy Ptprq autosomal dominant nonsyndromic deafness Myo6 , Pls1 autosomal dominant nonsyndromic deafness 11 Myo7a autosomal dominant nonsyndromic deafness 20 Actg1 autosomal dominant nonsyndromic deafness 22 Myo6 autosomal dominant nonsyndromic deafness 25 Slc17a8 autosomal dominant nonsyndromic deafness 30 Myo3a autosomal dominant nonsyndromic deafness 73 Ptprq autosomal dominant nonsyndromic deafness 76 Pls1 autosomal dominant nonsyndromic deafness 80 Myo7a autosomal dominant nonsyndromic deafness 90 Myo3a autosomal hemophilia A Pls3 autosomal recessive nonsyndromic deafness Adgrv1 , Cdh23 , Espn , Myo15a , Myo3a , Myo6 , Myo7a , Otof , Pcdh15 , Ptprq , Ush1c , Ush1g , Ush2a , Whrn autosomal recessive nonsyndromic deafness 12 Cdh23 Autosomal Recessive Nonsyndromic Deafness 18 Ush1c , Ush1g autosomal recessive nonsyndromic deafness 18A Ush1c , Ush1g autosomal recessive nonsyndromic deafness 2 Myo7a autosomal recessive nonsyndromic deafness 23 Pcdh15 autosomal recessive nonsyndromic deafness 3 Myo15a , Otof autosomal recessive nonsyndromic deafness 30 Myo3a autosomal recessive nonsyndromic deafness 31 Whrn autosomal recessive nonsyndromic deafness 36 Espn autosomal recessive nonsyndromic deafness 37 Myo6 autosomal recessive nonsyndromic deafness 7 Myo7a autosomal recessive nonsyndromic deafness 84A Ptprq autosomal recessive nonsyndromic deafness 9 Myo15a , Otof , Slc17a8 Baraitser-Winter syndrome Actb , Actg1 Baraitser-Winter syndrome 1 Actb , Actg1 Baraitser-Winter syndrome 2 Actg1 Bardet-Biedl syndrome Ush2a Becker Nevus Syndrome Actb beta-mannosidosis Adgrv1 , Cdh23 Bilateral Hearing Loss Myo3a Birt-Hogg-Dube syndrome Myo15a blindness Myo15a , Ush2a CAKUT Actg1 carcinoma Actb , Actg1 Chemical and Drug Induced Liver Injury Actb , Pls3 chromosome 1p36 deletion syndrome Espn cochlear disease Pcdh15 , Slc17a8 Cohen syndrome Myo7a coloboma Actb , Actg1 combined saposin deficiency Cdh23 common variable immunodeficiency 2 Myo15a cone-rod dystrophy Ush2a cone-rod dystrophy 3 Ush2a congenital diaphragmatic hernia Pls3 congenital nystagmus Myo7a CONGENITAL SMOOTH MUSCLE HAMARTOMA, WITH OR WITHOUT HEMIHYPERTROPHY Actb congenital stationary night blindness Ush2a congenital structural myopathy Ptprq COVID-19 Myo6 , Myo7a , Otof Craniofacial Abnormalities Actb , Actg1 Cutis Verticis Gyrata, Retinitis Pigmentosa, and Sensorineural Deafness Myo7a Deafness Cdh23 , Espn , Myo7a , Otof , Pcdh15 , Ptprq , Ush1g , Ush2a , Whrn Deafness, with Smith-Magenis Syndrome Myo15a Dwarfism Actb dysostosis Actb dystonia Actb Esophageal Neoplasms Actb essential tremor Myo6 Experimental Liver Cirrhosis Myo1c Experimental Mammary Neoplasms Actb , Actg1 factor VIII deficiency Pls3 familial adenomatous polyposis 1 Adgrv1 familial febrile seizures 1 Adgrv1 familial febrile seizures 4 Adgrv1 Febrile Seizures Actb fundus dystrophy Adgrv1 , Cdh23 , Espn , Myo7a , Pcdh15 , Ush1c , Ush1g , Ush2a , Whrn gastrointestinal stromal tumor Ush2a genetic disease Actb , Actg1 , Adgrv1 , Cdh23 , Espn , Myo15a , Myo3a , Myo6 , Myo7a , Otof , Pcdh15 , Pls1 , Pls3 , Ptprq , Slc17a8 , Ush1c , Ush1g , Ush2a , Whrn hand, foot and mouth disease Actb Hearing Loss Actg1 , Adgrv1 , Cdh23 , Espn , Myo15a , Myo3a , Myo6 , Myo7a , Otof , Pcdh15 , Pls1 , Ptprq , Ush1c , Ush1g , Ush2a , Whrn Hearing Loss, Noise-Induced Cdh23 hepatocellular carcinoma Actb hereditary breast ovarian cancer syndrome Myo7a Hereditary Neoplastic Syndromes Adgrv1 , Cdh23 Hirschsprung's disease Pcdh15 Hyperalgesia Slc17a8 hypertension Myo6 hypothyroidism Otof Hypoxia Actb Idiopathic Generalized Epilepsy Adgrv1 intellectual disability Actb , Actg1 , Myo7a , Ush1c Joubert syndrome Myo15a , Ush2a junctional epidermolysis bullosa with pyloric atresia Myo6 Juvenile-Onset Dystonia Actb Krabbe disease Cdh23 Leber congenital amaurosis Myo7a , Ush2a lissencephaly Actg1 Liver Neoplasms Pls1 Loeys-Dietz syndrome 4 Ush2a Lung Neoplasms Actb macular degeneration Ush2a male infertility Myo6 melanoma Myo7a Meniere's disease Adgrv1 , Cdh23 , Myo1c , Myo6 , Myo7a , Pcdh15 , Ush1c metabolic dysfunction-associated steatotic liver disease Actb metachromatic leukodystrophy Cdh23 Metachromatic Leukodystrophy due to Saposin B Deficiency Cdh23 microcephaly Actg1 Miller-Dieker lissencephaly syndrome Myo1c mitochondrial trifunctional protein deficiency Otof Myocardial Ischemia Actb Neoplasm Invasiveness Actb Neoplastic Cell Transformation Actg1 Nervous System Malformations Actb , Actg1 Neurodevelopmental Disorders Actb , Adgrv1 , Cdh23 , Espn nonsyndromic deafness Actg1 , Cdh23 , Myo15a , Myo3a , Myo6 , Myo7a , Otof , Pcdh15 , Ush2a Nonsyndromic Sensorineural Hearing Loss Cdh23 , Myo3a , Myo6 , Myo7a , Pcdh15 , Slc17a8 , Ush1g optic atrophy Adgrv1 , Cdh23 , Espn , Myo7a , Pcdh15 , Ush1c , Ush1g , Ush2a , Whrn osteoarthritis Actb , Pls3 osteogenesis imperfecta Pls3 osteoporosis Actg1 , Pls3 ovarian cancer Myo6 parathyroid carcinoma Ush2a Parkinsonism Slc17a8 Pendred syndrome Myo7a , Otof pituitary adenoma 5 Cdh23 pneumoconiosis Cdh23 Postmenopausal Osteoporosis Pls3 Potocki-Lupski syndrome Myo15a Presbycusis Actg1 , Cdh23 progressive myoclonus epilepsy 7 Ush1c prostate cancer Myo6 , Ush2a Pulmonary Surfactant Metabolism Dysfunction 2 Ush2a retinal degeneration Ush2a retinal disease Cdh23 retinitis pigmentosa Adgrv1 , Cdh23 , Myo7a , Pcdh15 , Ush1c , Ush1g , Ush2a retinitis pigmentosa 39 Ush2a retinitis pigmentosa-deafness syndrome Cdh23 , Myo7a , Pcdh15 , Ush1c , Ush1g , Ush2a , Whrn schizophrenia Pcdh15 sciatic neuropathy Slc17a8 Sensorineural Deafness with Hypertrophic Cardiomyopathy Myo6 sensorineural hearing loss Actb , Cdh23 , Espn , Myo15a , Myo3a , Myo6 , Myo7a , Otof , Pls1 , Ptprq , Ush1c , Ush2a , Whrn smooth muscle hamartoma Actb Stickler syndrome Cdh23 substance-related disorder Myo6 , Pcdh15 syndromic microphthalmia 5 Myo1c syndromic X-linked intellectual disability Lubs type Pls3 Tatton-Brown-Rahman syndrome Otof temporal lobe epilepsy Actb thrombocytopenia Actb Thrombocytopenia 8 Actb transient cerebral ischemia Slc17a8 trichinosis Slc17a8 Ullrich congenital muscular dystrophy 2 Myo6 Usher syndrome Adgrv1 , Cdh23 , Myo7a , Pcdh15 , Ush1c , Ush1g , Ush2a , Whrn Usher syndrome type 1 Adgrv1 , Cdh23 , Espn , Myo7a , Pcdh15 , Ush1c , Ush1g , Ush2a Usher Syndrome Type 1B Cdh23 , Myo7a , Pcdh15 , Ush1c Usher syndrome type 1C Ush1c Usher syndrome type 1D Cdh23 , Pcdh15 Usher syndrome type 1F Pcdh15 Usher syndrome type 1G Pcdh15 , Ush1g Usher Syndrome Type 1M Espn Usher syndrome type 2 Adgrv1 , Cdh23 , Myo7a , Ush1c , Ush2a Usher syndrome type 2A Adgrv1 , Cdh23 , Ush2a Usher Syndrome Type 2B Adgrv1 Usher syndrome type 2C Adgrv1 Usher syndrome type 2D Whrn Usher syndrome type 3A Ush2a Usher Syndrome, Type ID/F Cdh23 , Pcdh15 vestibular disease Espn , Myo7a Vision Disorders Ush2a Waardenburg syndrome Myo6