MYO6

Summary

MYO6 (myosin VI, HGNC:7605) is a protein-coding gene on chromosome 6q14.1, encoding Unconventional myosin-VI (Q9UM54). Myosins are actin-based motor molecules with ATPase activity.

This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 4646 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 970 total — 55 pathogenic, 45 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_004999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7605
Approved symbol	MYO6
Name	myosin VI
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0389
Ensembl gene	ENSG00000196586
Ensembl biotype	protein_coding
OMIM	600970
Entrez	4646

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 6 nonsense_mediated_decay, 1 retained_intron

ENST00000369975, ENST00000369977, ENST00000369985, ENST00000430435, ENST00000462633, ENST00000615563, ENST00000627432, ENST00000653423, ENST00000653917, ENST00000660420, ENST00000662184, ENST00000662603, ENST00000663400, ENST00000664209, ENST00000664640, ENST00000671923, ENST00000672093, ENST00000672162, ENST00000927893, ENST00000927894, ENST00000927895, ENST00000927896, ENST00000927897, ENST00000947980, ENST00000947981, ENST00000947982

RefSeq mRNA: 7 — MANE Select: NM_004999 NM_001300899, NM_001368136, NM_001368137, NM_001368138, NM_001368865, NM_001368866, NM_004999

CCDS: CCDS34487, CCDS75481, CCDS93948, CCDS93949, CCDS93950

Canonical transcript exons

ENST00000369977 — 35 exons

Exon	Start	End
ENSE00000797963	75892530	75892690
ENSE00000797964	75907605	75907708
ENSE00001027382	75891228	75891306
ENSE00001027384	75898373	75898411
ENSE00001027392	75895231	75895260
ENSE00001413891	75914813	75919537
ENSE00001426804	75749239	75749423
ENSE00002144831	75861023	75861095
ENSE00002148953	75848351	75848531
ENSE00002150623	75890057	75890265
ENSE00002155619	75817501	75817664
ENSE00002158868	75857097	75857254
ENSE00002161121	75886004	75886094
ENSE00002162496	75866526	75866621
ENSE00002162690	75911672	75911698
ENSE00002166761	75858902	75858993
ENSE00002170619	75830416	75830545
ENSE00002171556	75844897	75844977
ENSE00002172610	75908496	75908627
ENSE00002174053	75886844	75886994
ENSE00002174681	75841214	75841378
ENSE00002179233	75866932	75867105
ENSE00002182048	75835901	75835956
ENSE00002186410	75822782	75822851
ENSE00002187366	75832842	75832947
ENSE00002189621	75840585	75840682
ENSE00002194935	75855139	75855283
ENSE00002195738	75862596	75862723
ENSE00002198337	75914063	75914281
ENSE00002200953	75828540	75828613
ENSE00003518307	75879820	75879950
ENSE00003528802	75880043	75880120
ENSE00003604385	75873207	75873300
ENSE00003637744	75881689	75881818
ENSE00003637880	75870647	75870685

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0838 / max 922.6606, expressed in 1654 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68643	15.0182	1609
68645	4.4309	1354
68642	2.1385	1111
68644	1.7842	1002
68648	0.7120	151

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.38	gold quality
medial globus pallidus	UBERON:0002477	96.99	gold quality
corpus callosum	UBERON:0002336	96.97	gold quality
globus pallidus	UBERON:0001875	96.85	gold quality
sural nerve	UBERON:0015488	96.83	gold quality
lateral globus pallidus	UBERON:0002476	96.70	gold quality
pancreatic ductal cell	CL:0002079	96.16	gold quality
inferior vagus X ganglion	UBERON:0005363	96.16	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.89	gold quality
subthalamic nucleus	UBERON:0001906	95.83	gold quality
renal medulla	UBERON:0000362	95.74	gold quality
corpus epididymis	UBERON:0004359	95.74	gold quality
jejunal mucosa	UBERON:0000399	95.66	gold quality
endothelial cell	CL:0000115	95.47	gold quality
seminal vesicle	UBERON:0000998	95.38	gold quality
esophagus squamous epithelium	UBERON:0006920	95.09	gold quality
epithelium of nasopharynx	UBERON:0001951	95.07	gold quality
pylorus	UBERON:0001166	94.98	gold quality
caput epididymis	UBERON:0004358	94.90	gold quality
choroid plexus epithelium	UBERON:0003911	94.88	gold quality
bronchial epithelial cell	CL:0002328	94.84	gold quality
duodenum	UBERON:0002114	94.68	gold quality
substantia nigra pars compacta	UBERON:0001965	94.25	gold quality
islet of Langerhans	UBERON:0000006	94.09	gold quality
nephron tubule	UBERON:0001231	94.02	gold quality
nasal cavity epithelium	UBERON:0005384	93.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.63	gold quality
lower esophagus mucosa	UBERON:0035834	93.52	gold quality
oral cavity	UBERON:0000167	93.51	gold quality
squamous epithelium	UBERON:0006914	93.48	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	480.39
E-HCAD-10	yes	29.98
E-MTAB-7316	yes	22.90
E-CURD-112	yes	14.68
E-CURD-114	yes	7.04
E-MTAB-6075	no	2581.06
E-GEOD-106540	no	864.24
E-MTAB-8271	no	280.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU4F3, TP53

miRNA regulators (miRDB)

180 targeting MYO6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3692-3P	99.98	70.27	2139

Literature-anchored findings (GeneRIF, showing 40)

• In families with recessively inherited deafness, DFNB37, our sequence analyses of MYO6 reveal a frameshift mutation (36-37insT), a nonsense mutation (R1166X), and a missense mutation (E216V) (PMID:12687499)
• Results report the effects of the C442Y mutation on the kinetics of the actomyosin ATP hydrolysis mechanism and motor function of myosin VI. (PMID:15123708)
• Inhibiting myosin VI expression in high-grade ovarian carcinoma cells impeded cell spreading and migration in vitro; optical imaging and histopathologic studies revealed that inhibiting myosin VI expression reduces tumor dissemination in nude mice (PMID:15146066)
• myosin VI and Dab2 facilitate CFTR endocytosis by a mechanism that requires actin filaments (PMID:15247260)
• a novel function for p53 in the maintenance of Golgi complex integrity and for myosin VI in the p53-dependent prosurvival pathway. (PMID:16507995)
• Myosin VI modulates RNAPII-dependent transcription of active genes, implicating the possibility of an actin-myosin based mechanism of transcription. (PMID:16949370)
• These results support that myosin VI is critical in maintaining the malignant properties of the majority of human prostate cancers diagnosed today. (PMID:17071605)
• We have identified three binding sites in the Myosin VI carboxy-terminal: a WWY motif for Disabled-2, a RRL motif for glucose-transporter binding protein and optineurin binding and a site that binds specifically to PtdIns(4,5)P2-containing liposomes. (PMID:17187061)
• results suggest that myosin VI-T6BP-NDP52 complexes may play a role in coordinating cytokine signalling and membrane transport pathways with actin filament organisation and cell adhesion (PMID:17635994)
• Results are consistent with vesicle-associated myosin VI existing as a processive dimer, capable of its known trafficking function. (PMID:17683200)
• Myosin VI and LMTK2 are required for the transport of cargo, such as the Transferrin Receptor, from early endosomes to the endocytic recycling compartment. (PMID:18029400)
• inner ear hair cells are sensitive to changes in expression levels of MYO6 (PMID:18212818)
• In conclusion, a novel nonsense MYO6 mutation causes post-lingual, slowly progressive autosomal dominant nonsyndromic moderate to severe hearing loss in a Danish family. (PMID:18348273)
• Results show that BREK is critical for the transition of endocytosed membrane vesicles from early endosomes to recycling endosomes and also suggest an involvement of myosin VI in this pathway. (PMID:18429820)
• Golgi apparatus in prostate cancer cells differs from the normal Golgi by elevated levels of two molecules, GOLPH2 and MYO6. (PMID:18543251)
• Data show that downregulation of myosin VI expression results in a significant reduction in PSA and VEGF secretion in LNCaP cells, and the intracellular targeting seems to involve myosin VI-interacting proteins, GIPC and LMTK2 and Dab2. (PMID:19855435)
• This study describes the phenotype of 2 Belgian families with SNHL linked to DFNA22, both with a pathogenic change in the deafness gene MYO6. (PMID:19893302)
• Our data indicate that miR-143 and miR-145 are involved in the regulation of MYO6 expression and possibly in the development of prostate cancer. (PMID:20353999)
• Myosin VI is differentially regulated by DNA damage in p53- and cell type-dependent manners. (PMID:20576604)
• In migratory cells ablation of myosin VI or optineurin inhibits the polarized delivery of the epidermal growth factor receptor into the leading edge and leads to profound defects in lamellipodia formation. (PMID:20604900)
• Study suggests 2 tilt angles during myo6 stepping, corresponding to the pre- & post powerstroke states regulating leading head; large steps with hand-over-hand mechanism & small steps with inchworm-like mechanism increasing in frequency with ADP. (PMID:20850010)
• results suggest a novel role for myosin VI and optineurin in regulation of fusion pores formed between secretory vesicles and the plasma membrane during the final stages of secretion (PMID:21148290)
• Role of insert-1 of myosin VI in modulating nucleotide affinity. (PMID:21278381)
• In this review, we describe the structure, kinetic properties and functions proposed for myosin VI, and present current hypotheses on the mechanisms of functioning of this unique protein in vivo. (PMID:21735821)
• Studies from crystallographic structures of myosin VI have revealed that rearrangements within the converter subdomain occur. (PMID:22171985)
• myosin VI regulates the organization of actin dynamics at the surface of a specialized organelle (PMID:22321127)
• detailed kinetic characterization of the myosin-6 motor domain (PMID:22884421)
• analysis of the dynamic exchange of myosin VI on endocytic structures (PMID:22992744)
• The central regions of the cadherin tail adjacent to the juxtamembrane sequence also display binding activity for Myo VI-CBD. (PMID:23007415)
• It was shown that that myosin VI, in concert with Tom1, plays a crucial role in autophagy. Tom1 was identified as a myosin VI binding partner on endosomes. (PMID:23023224)
• Report Dutch family with progressive autosomal dominant sensorineural hearing loss caused by a mutation in MYO6 resembling presbyacusis. (PMID:23340379)
• we identified a novel MYO6 mutation at the splice acceptor site of exon 7 (c.554-1G>A) in an extended German family with autosomal dominant postlingual non-syndromic hearing impairment. (PMID:23635807)
• Myo6 plays a critical role in the fusion of endosome/lysosome in Rmc epithelial cells. Deficiency of myo6 compromises the epithelial barrier function (PMID:24028494)
• Data indicate nine novel mutations in the genes encoding myosin VI, myosin VIIA and myosin XVA in hearing-impaired individuals from Israeli Jewish and Palestinian Arab families. (PMID:24105371)
• Myosin VI mediates the movement of NHE3 to the microvillus in intestinal epithelial cells. (PMID:24928903)
• Three mutations (p.R825X, p.R991X and Q918fsX941) produce a premature truncation of the myosin VI protein. p.R205Q, was associated with diminished actin-activated ATPase activity and actin gliding velocity of myosin VI in an in vitro analysis. (PMID:25080041)
• In myopathies associated with fiber atrophy, the amount of MVI was enhanced and its localization in affected fibers was changed. (PMID:25125183)
• The frameshift deletion in MYO6 was confirmed as the causative variant for this dominant nonsyndromic hearing loss DFNA22 family (PMID:25227905)
• MYO6 is crucial in maintaining cell cycle and cell growth of lung cancer cells.MYO6 is highly expressed in human lung cancer tissues. (PMID:25643992)
• MYO6 was highly expressed in hepatocellular carcinoma. (PMID:25703929)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	myo6b	ENSDARG00000042141
danio_rerio	myo6a	ENSDARG00000044016
mus_musculus	Myo6	ENSMUSG00000033577
rattus_norvegicus	Myo6	ENSRNOG00000011852
drosophila_melanogaster	jar	FBGN0011225
caenorhabditis_elegans	spe-15	WBGENE00004969

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Unconventional myosin-VI — Q9UM54 (reviewed: Q9UM54)

Alternative names: Unconventional myosin-6

All UniProt accessions (15): Q9UM54, A0A0A0MRM8, A0A0D9SGC1, A0A1Y0BRN3, A0A590UJ40, A0A590UJ48, A0A590UJ75, A0A590UJW9, A0A590UJY4, A0A590UK22, A0A590UK71, A0A590UK86, A0A590UKB0, A0A5F9ZI03, Q5JVM0

UniProt curated annotations — full annotation on UniProt →

Function. Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. Together with TOM1, mediates delivery of endocytic cargo to autophagosomes thereby promoting autophagosome maturation and driving fusion with lysosomes. Links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN. May act as a regulator of F-actin dynamics. As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. May play a role in the extension and network organization of neurites. Required for structural integrity of inner ear hair cells. Required for the correct localization of CLIC5 and RDX at the stereocilium base. Modulates RNA polymerase II-dependent transcription.

Subunit / interactions. Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding. Able to function as a monomer under specific conditions in vitro. Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells. Component of the DISP/DOCK7-induced septin displacement complex, at least composed of DOCK7, LRCH3 and MYO6. Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal. This interaction occurs only if the C-terminal lobe of calmodulin is occupied by calcium. Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells. Interacts with DAB2. In vitro, the C-terminal globular tail binds a C-terminal region of DAB2. Interacts with CFTR. Interacts with CABP5. Interacts with TOM1. Interacts with OPTN. Interacts with TAX1BP1 and CALCOCO2/NDP52. Interacts with TOM1L2. Interacts with CLIC5; may work together in a complex which also includes RDX and MYO6 to stabilize linkages between the plasma membrane and subjacent actin cytoskeleton at the base of stereocilia.

Subcellular location. Golgi apparatus. trans-Golgi network membrane. Nucleus. Cytoplasm. Perinuclear region. Membrane. Clathrin-coated pit. Cytoplasmic vesicle. Clathrin-coated vesicle. Cell projection. Filopodium. Ruffle membrane. Microvillus. Cytosol. Autophagosome. Endosome Cytoplasmic vesicle. Clathrin-coated vesicle membrane Cytoplasmic vesicle. Clathrin-coated vesicle membrane.

Tissue specificity. Expressed in most tissues examined including heart, brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in brain, pancreas, testis and small intestine. Also expressed in fetal brain and cochlea. Isoform 1 and isoform 2, containing the small insert, and isoform 4, containing neither insert, are expressed in unpolarized epithelial cells.

Post-translational modifications. Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK).

Disease relevance. Deafness, autosomal dominant, 22 (DFNA22) [MIM:606346] 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. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal recessive, 37 (DFNB37) [MIM:607821] 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. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy (DFNHCM) [MIM:606346] An autosomal dominant sensorineural deafness associated with hypertrophic cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding. The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. Its contribution to the mechanism conferring the myosin movement on actin filaments is debated.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UM54-3	3	yes
Q9UM54-1	1
Q9UM54-2	2
Q9UM54-4	4
Q9UM54-5	5
Q9UM54-6	6

RefSeq proteins (7): NP_001287828, NP_001355065, NP_001355066, NP_001355067, NP_001355794, NP_001355795, NP_004990* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001609	Myosin_head_motor_dom-like	Domain
IPR004009	SH3_Myosin	Domain
IPR008989	Myosin_S1_N	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032412	Myosin-VI_CBD	Domain
IPR036114	MYSc_Myo6	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR049016	MYO6_lever	Domain

Pfam: PF00063, PF16521, PF21521

UniProt features (46 total): helix 14, region of interest 9, modified residue 5, splice variant 4, strand 4, domain 3, sequence variant 3, chain 1, binding site 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6J56	X-RAY DIFFRACTION	1.8
8W41	ELECTRON MICROSCOPY	3.54
2N0Z	SOLUTION NMR
2N10	SOLUTION NMR
2N11	SOLUTION NMR
2N12	SOLUTION NMR
2N13	SOLUTION NMR
6E5N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UM54-F1	79.07	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 151–158

Post-translational modifications (5): 267, 405, 604, 1025, 1155

Mutagenesis-validated functional residues (1):

Position	Phenotype
1116–1118	decreased localization to autophagosomes.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-190873	Gap junction degradation
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-157858	Gap junction trafficking and regulation
R-HSA-162582	Signal Transduction
R-HSA-190828	Gap junction trafficking
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199991	Membrane Trafficking
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 349 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, JAEGER_METASTASIS_DN, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOZGIT_ESR1_TARGETS_DN, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, REACTOME_MEMBRANE_TRAFFICKING, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT, ONKEN_UVEAL_MELANOMA_UP, WOO_LIVER_CANCER_RECURRENCE_UP

GO Biological Process (12): intracellular protein transport (GO:0006886), endocytosis (GO:0006897), actin filament organization (GO:0007015), sensory perception of sound (GO:0007605), intracellular protein localization (GO:0008104), response to xenobiotic stimulus (GO:0009410), actin filament-based movement (GO:0030048), DNA damage response, signal transduction by p53 class mediator (GO:0030330), inner ear morphogenesis (GO:0042472), inner ear auditory receptor cell differentiation (GO:0042491), regulation of secretion (GO:0051046), protein transport (GO:0015031)

GO Molecular Function (11): microfilament motor activity (GO:0000146), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779), calmodulin binding (GO:0005516), ATP binding (GO:0005524), identical protein binding (GO:0042802), ADP binding (GO:0043531), actin filament binding (GO:0051015), minus-end directed microfilament motor activity (GO:0060001), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (32): ruffle (GO:0001726), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endosome (GO:0005768), autophagosome (GO:0005776), Golgi apparatus (GO:0005794), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), microvillus (GO:0005902), clathrin-coated pit (GO:0005905), cell cortex (GO:0005938), actin cytoskeleton (GO:0015629), membrane (GO:0016020), unconventional myosin complex (GO:0016461), endocytic vesicle (GO:0030139), filopodium (GO:0030175), clathrin-coated vesicle membrane (GO:0030665), cytoplasmic vesicle (GO:0031410), filamentous actin (GO:0031941), nuclear membrane (GO:0031965), ruffle membrane (GO:0032587), apical part of cell (GO:0045177), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), myosin complex (GO:0016459), clathrin-coated vesicle (GO:0030136), protein-containing complex (GO:0032991), cell projection (GO:0042995), clathrin-coated endocytic vesicle (GO:0045334)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RHOBTB GTPase Cycle	2
RHO GTPase cycle	2
Gap junction trafficking	1
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
Transmission across Chemical Synapses	1
Neuronal System	1
Membrane Trafficking	1
Gap junction trafficking and regulation	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Vesicle-mediated transport	1
Neurotransmitter receptors and postsynaptic signal transmission	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endomembrane system	3
cytoplasm	3
intracellular protein localization	2
protein binding	2
adenyl ribonucleotide binding	2
intracellular membrane-bounded organelle	2
cytoplasmic vesicle	2
membrane	2
cell periphery	2
actin-based cell projection	2
protein transport	1
intracellular transport	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
sensory perception of mechanical stimulus	1
macromolecule localization	1
response to chemical	1
actin filament-based process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
hair cell differentiation	1
inner ear receptor cell differentiation	1
secretion	1
regulation of transport	1
transport	1
establishment of protein localization	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
molecular_function	1
cytoskeletal protein binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

2097 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO6	GIPC1	O14908	967
MYO6	OTOF	Q9HC10	924
MYO6	OPTN	Q96CV9	804
MYO6	DAB2	P98082	775
MYO6	TMPRSS3	P57727	735
MYO6	DOCK7	Q96N67	718
MYO6	TPRN	Q4KMQ1	715
MYO6	RGS19	P49795	706
MYO6	LRP2	P98164	700
MYO6	TMPRSS4	Q9NRS4	670
MYO6	CDH23	Q9H251	667
MYO6	KCNQ4	P56696	645
MYO6	SLC26A5	P58743	644
MYO6	TMC1	Q8TDI8	638
MYO6	CACNA1D	Q01668	632

IntAct

230 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
TOLLIP	TOM1	psi-mi:“MI:0914”(association)	0.890
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
LRCH3	DOCK7	psi-mi:“MI:0914”(association)	0.840
DOCK7	LRCH3	psi-mi:“MI:0914”(association)	0.840
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
SH3BP4	GIPC1	psi-mi:“MI:0914”(association)	0.740
MYO6	LRCH3	psi-mi:“MI:0915”(physical association)	0.730
ARHGEF12	GIPC1	psi-mi:“MI:0914”(association)	0.720
ARHGEF12	GIPC1	psi-mi:“MI:2364”(proximity)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MYO6	ARHGEF12	psi-mi:“MI:0403”(colocalization)	0.700
MYO6	GIPC1	psi-mi:“MI:0915”(physical association)	0.690
MYO6	GIPC1	psi-mi:“MI:0914”(association)	0.690
MYO6	TOM1L2	psi-mi:“MI:0915”(physical association)	0.610
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
FBXO30	MYO6	psi-mi:“MI:0915”(physical association)	0.560
MYO6	ENTREP1	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (645): MYO6 (Affinity Capture-MS), MYO6 (Affinity Capture-RNA), MYO6 (Affinity Capture-RNA), MYO6 (Affinity Capture-RNA), MYO6 (Affinity Capture-MS), MYO6 (Affinity Capture-MS), MYO6 (Reconstituted Complex), MYO6 (Affinity Capture-MS), DPP9 (Co-fractionation), MYO6 (Co-fractionation), MYO6 (Co-fractionation), MYO6 (Co-fractionation), MYO6 (Co-fractionation), MYO6 (Co-fractionation), NHLRC2 (Co-fractionation)

ESM2 similar proteins: A1C4A5, A1DBH2, A2R5J1, A3LYL7, A4RE77, A5DKH0, A5E4A8, A6SED8, A6ZMG6, A7EK16, A8N2Y6, A8PWF6, B0CRJ3, B0Y9Q4, E1BPK6, E9Q634, G3UW82, O00160, P0CP00, P0CP01, P12882, P13538, P49824, Q00647, Q04439, Q076A6, Q076A7, Q0CEX5, Q12965, Q1DLP2, Q28641, Q2HDI2, Q2US45, Q4WC55, Q59MQ0, Q63356, Q64331, Q6BUQ2, Q6C7C0, Q6CVE9

Diamond homologs: A8PWF6, B2RTY4, D3ZJP6, E1BPK6, E7EZG2, E7F3F0, E7F9L8, E9Q634, F1PT61, F4HWY6, F4HXP9, F4I460, F4I507, F4I5Q6, F4IRU3, F4IUG9, F4IVR7, F4JIU4, F4JM19, F4K0A6, F4K5J1, F8VQB6, K7U9N8, O00160, O08638, O74805, O94477, P08799, P10569, P10587, P11055, P12844, P12847, P13541, P14105, P19706, P21271, P22467, P24733, P32492

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PAK3	“up-regulates activity”	MYO6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 204 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	5	14.3×	3e-03
Constitutive Signaling by Aberrant PI3K in Cancer	9	8.6×	9e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	9	6.5×	2e-03
PIP3 activates AKT signaling	11	5.5×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to type II interferon	9	10.5×	3e-04
protein autophosphorylation	8	6.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

970 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	45
Uncertain significance	482
Likely benign	168
Benign	100

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073626	NM_004999.4(MYO6):c.2571_2574del (p.Ser858fs)	Pathogenic
1297599	NM_004999.4(MYO6):c.2761G>T (p.Glu921Ter)	Pathogenic
1452617	NM_004999.4(MYO6):c.2974C>T (p.Gln992Ter)	Pathogenic
1458447	NM_004999.4(MYO6):c.3256_3257dup (p.Asp1087fs)	Pathogenic
1676028	NM_004999.4(MYO6):c.1859T>A (p.Leu620Ter)	Pathogenic
1679197	NM_004999.4(MYO6):c.560del (p.Pro187fs)	Pathogenic
1684065	NM_004999.4(MYO6):c.2867+1G>A	Pathogenic
1693367	NM_004999.4(MYO6):c.2287-2A>G	Pathogenic
178957	NM_004999.4(MYO6):c.238C>T (p.Arg80Ter)	Pathogenic
2021491	NM_004999.4(MYO6):c.3376del (p.Thr1126fs)	Pathogenic
2029461	NM_004999.4(MYO6):c.2117dup (p.Ser707fs)	Pathogenic
2034241	NM_004999.4(MYO6):c.2240dup (p.Asn747fs)	Pathogenic
2055978	NM_004999.4(MYO6):c.1125del (p.Cys375fs)	Pathogenic
2070231	NM_004999.4(MYO6):c.854_855del (p.Lys285fs)	Pathogenic
228375	NM_004999.4(MYO6):c.2814_2815del (p.Arg939fs)	Pathogenic
228376	NM_004999.4(MYO6):c.458C>G (p.Ser153Ter)	Pathogenic
236034	NM_004999.4(MYO6):c.1473_1473+2delinsC	Pathogenic
2637184	NM_004999.4(MYO6):c.613C>T (p.Arg205Ter)	Pathogenic
2657164	GRCh37/hg19 6q14.1(chr6:76545618-76545673)x1	Pathogenic
2698497	NM_004999.4(MYO6):c.2692del (p.Glu898fs)	Pathogenic
2707703	NM_004999.4(MYO6):c.256del (p.Ile86fs)	Pathogenic
2734912	NM_004999.4(MYO6):c.554-1G>A	Pathogenic
2734913	NM_004999.4(MYO6):c.2473C>T (p.Arg825Ter)	Pathogenic
2734914	NM_004999.4(MYO6):c.2544dup (p.Arg849fs)	Pathogenic
2825213	NM_004999.4(MYO6):c.3040dup (p.Leu1014fs)	Pathogenic
2831928	NM_004999.4(MYO6):c.1452_1453insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGTCTTCAACAATTTTTT (p.Asn485delinsPhePhePhePhePhePheXaaXaaXaaXaaGluGlyGluGlyGluGlyGluGlyGluGlyGluGlyGluGlyGluGlyGluGlyGluSerSerThrIlePheTer)	Pathogenic
2864948	NM_004999.4(MYO6):c.2800G>T (p.Glu934Ter)	Pathogenic
3246186	NC_000006.11:g.(?76568599)(76568730_?)del	Pathogenic
3246189	NC_000006.11:g.(?76527265)(76545693_?)del	Pathogenic
3257374	NM_004999.4(MYO6):c.856G>T (p.Glu286Ter)	Pathogenic

SpliceAI

6076 predictions. Top by Δscore:

Variant	Effect	Δscore
6:75817493:T:A	acceptor_gain	1.0000
6:75817496:A:AG	acceptor_gain	1.0000
6:75817496:AACAG:A	acceptor_gain	1.0000
6:75817497:ACAGG:A	acceptor_gain	1.0000
6:75817498:C:G	acceptor_gain	1.0000
6:75817498:CAG:C	acceptor_loss	1.0000
6:75817498:CAGGT:C	acceptor_gain	1.0000
6:75817499:A:AG	acceptor_gain	1.0000
6:75817499:A:T	acceptor_loss	1.0000
6:75817499:AG:A	acceptor_gain	1.0000
6:75817499:AGGT:A	acceptor_gain	1.0000
6:75817499:AGGTG:A	acceptor_gain	1.0000
6:75817500:G:A	acceptor_loss	1.0000
6:75817500:G:GT	acceptor_gain	1.0000
6:75817500:GG:G	acceptor_gain	1.0000
6:75817500:GGT:G	acceptor_gain	1.0000
6:75817500:GGTG:G	acceptor_gain	1.0000
6:75817500:GGTGA:G	acceptor_gain	1.0000
6:75817660:GCAAG:G	donor_gain	1.0000
6:75817661:C:T	donor_gain	1.0000
6:75817662:AAGG:A	donor_loss	1.0000
6:75817663:AGG:A	donor_loss	1.0000
6:75817665:G:GG	donor_gain	1.0000
6:75817665:GT:G	donor_loss	1.0000
6:75817666:T:G	donor_loss	1.0000
6:75822780:A:AG	acceptor_gain	1.0000
6:75822781:G:GG	acceptor_gain	1.0000
6:75828610:TTATG:T	donor_loss	1.0000
6:75828611:TATGT:T	donor_loss	1.0000
6:75828612:ATGT:A	donor_loss	1.0000

AlphaMissense

8573 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004167 (6:75889875 T>A), RS1000009266 (6:75857601 A>T), RS1000074992 (6:75901009 G>A,C), RS1000089288 (6:75808721 G>A), RS1000093261 (6:75769644 G>A), RS1000119383 (6:75850736 T>G), RS1000129280 (6:75895748 C>G), RS1000137093 (6:75793144 C>T), RS1000138841 (6:75811254 A>G), RS1000188951 (6:75757503 G>C,T), RS1000254979 (6:75883022 T>C), RS1000265301 (6:75806475 A>G), RS1000265391 (6:75906473 C>A,G,T), RS1000272584 (6:75764035 C>A), RS1000273120 (6:75776542 GCCA>G)

Disease associations

OMIM: gene MIM:600970 | disease phenotypes: MIM:606346, MIM:607821, MIM:128600, MIM:156000, MIM:124900, MIM:193500, MIM:190300, MIM:226730

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss 22	Definitive	Autosomal dominant
nonsyndromic genetic hearing loss	Definitive	Autosomal dominant
autosomal recessive nonsyndromic hearing loss 37	Strong	Autosomal recessive
progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome	Supportive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AD

Mondo (15): hearing loss disorder (MONDO:0005365), autosomal dominant nonsyndromic hearing loss 22 (MONDO:0011660), autosomal recessive nonsyndromic hearing loss 37 (MONDO:0011912), ear malformation (MONDO:0007500), nonsyndromic genetic hearing loss (MONDO:0019497), Meniere disease (MONDO:0007972), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), Waardenburg syndrome (MONDO:0018094), obesity disorder (MONDO:0011122), infertility disorder (MONDO:0005047), male infertility (MONDO:0005372), essential tremor (MONDO:0003233), junctional epidermolysis bullosa with pyloric atresia (MONDO:0009183), progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome (MONDO:0016424), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (11): Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome (Orphanet:228012), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare non-syndromic genetic deafness (Orphanet:87884), Rare genetic deafness (Orphanet:96210), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Waardenburg syndrome (Orphanet:3440), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Junctional epidermolysis bullosa with pyloric atresia (Orphanet:79403), NON RARE IN EUROPE: Menière disease (Orphanet:45360), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

8 total (9 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0001751	Abnormal vestibular function
HP:0003577	Congenital onset
HP:0007642	Early-onset non-progressive night blindness
HP:0001513	Obesity

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002606_2	Prostate cancer	4.000000e-08
GCST006192_41	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-08
GCST012226_480	Waist circumference adjusted for body mass index	9.000000e-09
GCST90020028_502	Hip circumference adjusted for BMI	5.000000e-09
GCST90020028_503	Hip circumference adjusted for BMI	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D007246	Infertility	C12.100.750
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D008575	Meniere Disease	C09.218.568.217.500
D014849	Waardenburg Syndrome	C16.131.077.938
C564609	Deafness, Autosomal Recessive (supp.)
C564331	Deafness, Autosomal Recessive 37 (supp.)
C538197	Deafness, autosomal dominant nonsyndromic sensorineural 22 (supp.)
C535377	Epidermolysis bullosa with pyloric atresia (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	4
Benzo(a)pyrene	increases methylation, increases expression	3
mono-(2-ethylhexyl)phthalate	decreases expression	2
bicalutamide	increases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
geraniol	increases expression	1
sodium arsenate	decreases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
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NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
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