MYO6

myosin VI, the group of Myosin heavy chains, class VI

Basic information

Region (hg38): 6:75749200-75919537

Previous symbols: [ "DFNA22", "DFNB37" ]

Links

ENSG00000196586 ∙ NCBI:4646 ∙ OMIM:600970 ∙ HGNC:7605 ∙ Uniprot:Q9UM54 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 22 (Strong), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 37 (Strong), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 22 (Strong), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 37 (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 22; Deafness, autosomal recessive 37	AD/AR	Audiologic/Otolaryngologic	Deafness, autosomal dominant 22 may involve hypertrophic cardiomyopathy, and awareness may enable early identification and management of cardiac manifestations; In Deafness, autosomal recessive 37, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	11468689; 12687499; 15060111; 18212818; 18348273; 19893302; 28000701; 29044474; 29224747
One kindred has been described also segregating hypertrophic cardiomyopathy with the MYO6 variant, but the overall evidence appears mixed as relates to cardiac findings

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO6 gene.

• not provided (457 variants)
• Autosomal dominant nonsyndromic hearing loss 22 (189 variants)
• Autosomal recessive nonsyndromic hearing loss 37 (180 variants)
• not specified (104 variants)
• Inborn genetic diseases (26 variants)
• Nonsyndromic Hearing Loss, Dominant (14 variants)
• Nonsyndromic Hearing Loss, Recessive (14 variants)
• Hearing impairment (12 variants)
• MYO6-related condition (12 variants)
• Rare genetic deafness (12 variants)
• Nonsyndromic genetic hearing loss (7 variants)
• Autosomal dominant nonsyndromic hearing loss 22;Autosomal recessive nonsyndromic hearing loss 37 (5 variants)
• Autosomal recessive nonsyndromic hearing loss 37;Autosomal dominant nonsyndromic hearing loss 22 (4 variants)
• Infertility disorder;Male infertility (1 variants)
• Sensorineural deafness with hypertrophic cardiomyopathy (1 variants)
• MYO6-Related Disorders (1 variants)
• Autosomal dominant nonsyndromic hearing loss (1 variants)
• Ear malformation (1 variants)
• Essential tremor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	37	1	45
missense		6	215	8	2	231
nonsense	10	7	1			18
start loss						0
frameshift	15	8	4			27
inframe indel			4			4
splice donor/acceptor (+/-2bp)	3	9	1			13
splice region			12	11		23
non coding			67	96	90	253
Total	28	30	299	141	93

Highest pathogenic variant AF is 0.0000341

Variants in MYO6

This is a list of pathogenic ClinVar variants found in the MYO6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-75749210-G-A		Nonsyndromic Hearing Loss, Recessive • Nonsyndromic Hearing Loss, Dominant	Uncertain significance (Jun 14, 2016)
6-75749246-G-C		Autosomal dominant nonsyndromic hearing loss 22 • Autosomal recessive nonsyndromic hearing loss 37	Conflicting classifications of pathogenicity (May 26, 2021)
6-75749286-G-T		Autosomal recessive nonsyndromic hearing loss 37 • Autosomal dominant nonsyndromic hearing loss 22	Uncertain significance (Jan 13, 2018)
6-75749422-C-G		Autosomal dominant nonsyndromic hearing loss 22 • Autosomal recessive nonsyndromic hearing loss 37	Conflicting classifications of pathogenicity (May 15, 2021)
6-75749465-G-T			Benign (May 13, 2021)
6-75817254-A-G			Benign (Nov 29, 2018)
6-75817304-C-A			Likely benign (Aug 06, 2019)
6-75817304-C-CA			Benign (Sep 09, 2019)
6-75817304-C-CAAAA			Benign (Sep 08, 2019)
6-75817304-C-CAAAAA			Likely benign (Sep 19, 2019)
6-75817319-A-G			Benign (Aug 13, 2019)
6-75817326-G-A			Likely benign (Dec 22, 2018)
6-75817335-G-A			Benign (Dec 17, 2018)
6-75817344-C-T			Likely benign (Dec 31, 2018)
6-75817498-C-G			Uncertain significance (Oct 23, 2023)
6-75817529-C-A		Autosomal dominant nonsyndromic hearing loss 22 • Autosomal recessive nonsyndromic hearing loss 37	Uncertain significance (Feb 02, 2018)
6-75817534-ATCC-A		not specified	not provided (Jan 28, 2014)
6-75817551-G-A			Uncertain significance (Jan 18, 2022)
6-75817565-C-T		not specified	Likely benign (Apr 28, 2021)
6-75817573-C-T		Autosomal recessive nonsyndromic hearing loss 37 • Autosomal dominant nonsyndromic hearing loss 22	Uncertain significance (May 31, 2019)
6-75817574-G-A		not specified	Likely benign (Apr 18, 2023)
6-75817582-C-CT		Autosomal recessive nonsyndromic hearing loss 37	Pathogenic (May 01, 2003)
6-75817592-A-G			Likely benign (Jun 16, 2021)
6-75817599-A-G		not specified	Uncertain significance (Jul 06, 2021)
6-75817608-A-G			Uncertain significance (Apr 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO6	protein_coding	protein_coding	ENST00000369977	34	170346

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000243	1.00	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	586	689	0.851	0.0000378	8555
Missense in Polyphen		85	94.302	0.90136		1092
Synonymous	0.593	219	230	0.950	0.0000118	2251
Loss of Function	5.92	25	83.4	0.300	0.00000480	971

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000714	0.000713
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000109	0.000109
South Asian	0.000327	0.000327
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: 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. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity). {ECO:0000250, ECO:0000269|PubMed:10519557, ECO:0000269|PubMed:11447109, ECO:0000269|PubMed:16507995, ECO:0000269|PubMed:16949370}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:11468689}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:12687499}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy (DFNHCM) [MIM:606346]: An autosomal dominant sensorineural deafness associated with hypertrophic cardiomyopathy. {ECO:0000269|PubMed:15060111}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: VEGFA-VEGFR2 Signaling Pathway;Vesicle-mediated transport;Membrane Trafficking;Neuronal System;EGFR1;Trafficking of AMPA receptors;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation;Stabilization and expansion of the E-cadherin adherens junction (Consensus)

Recessive Scores

• pRec: 0.319

Intolerance Scores

• loftool: 0.179
• rvis_EVS: -0.37
• rvis_percentile_EVS: 28.26

Haploinsufficiency Scores

• pHI: 0.261
• hipred: Y
• hipred_score: 0.698
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.301

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Myo6
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: myo6a
• Affected structure: angioblastic mesenchymal cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: intracellular protein transport;endocytosis;sensory perception of sound;actin filament-based movement;DNA damage response, signal transduction by p53 class mediator;response to drug;positive regulation of transcription by RNA polymerase II;regulation of secretion
• Cellular component: ruffle;nucleus;nucleoplasm;cytoplasm;lysosomal membrane;Golgi apparatus;cytosol;actin filament;plasma membrane;microvillus;clathrin-coated pit;cell cortex;membrane;unconventional myosin complex;RNA polymerase II, holoenzyme;endocytic vesicle;clathrin-coated vesicle membrane;cytoplasmic vesicle;filamentous actin;nuclear membrane;ruffle membrane;apical part of cell;clathrin-coated endocytic vesicle;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: motor activity;actin binding;protein binding;calmodulin binding;ATP binding;ADP binding;actin filament binding;minus-end directed microfilament motor activity