MYO7A

myosin VIIA, the group of FERM domain containing|Myosin heavy chains, class VII|A-kinase anchoring proteins

Basic information

Region (hg38): 11:77128246-77215241

Previous symbols: [ "USH1B", "DFNB2", "DFNA11" ]

Links

ENSG00000137474 ∙ NCBI:4647 ∙ OMIM:276903 ∙ HGNC:7606 ∙ Uniprot:Q13402 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 11 (Strong), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 2 (Limited), mode of inheritance: AR
• Usher syndrome type 1 (Strong), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss 11 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Usher syndrome type 1 (Supportive), mode of inheritance: AR
• Usher syndrome type 2 (Supportive), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss 11 (Strong), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 2 (Moderate), mode of inheritance: AR
• Usher syndrome type 1B (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 2 (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 2 (Strong), mode of inheritance: AR
• Usher syndrome type 1B (Strong), mode of inheritance: AR
• Usher syndrome type 1 (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 recessive 2; Usher syndrome, type I	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	7951250; 8776602; 9171832; 7870171; 9171833; 11391666; 11889386; 15221449; 18181211; 20132242; 21436283; 21150918; 23226338
The timing of onset has been reported as highly variable, though heterozygous variants appear to result in postlingual onset

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO7A gene.

• not_provided (3951 variants)
• Usher_syndrome_type_1 (755 variants)
• Usher_syndrome_type_1B (722 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_2 (717 variants)
• Autosomal_dominant_nonsyndromic_hearing_loss_11 (465 variants)
• not_specified (408 variants)
• Inborn_genetic_diseases (264 variants)
• MYO7A-related_disorder (159 variants)
• Retinal_dystrophy (108 variants)
• Rare_genetic_deafness (104 variants)
• Usher_syndrome (89 variants)
• Hearing_loss,_autosomal_recessive (30 variants)
• Hearing_impairment (24 variants)
• Nonsyndromic_genetic_hearing_loss (13 variants)
• Meniere_disease (9 variants)
• Retinitis_pigmentosa (9 variants)
• Ear_malformation (7 variants)
• Deafness (7 variants)
• Usher_syndrome_type_2 (3 variants)
• Sensorineural_hearing_loss_disorder (3 variants)
• Auditory_neuropathy (3 variants)
• Retinitis_pigmentosa-deafness_syndrome (2 variants)
• Hearing_loss (2 variants)
• Nonsyndromic_Hearing_Loss,_Dominant (2 variants)
• Cone-rod_dystrophy (2 variants)
• Global_developmental_delay (2 variants)
• See_cases (2 variants)
• Monogenic_hearing_loss (2 variants)
• Childhood_onset_hearing_loss (2 variants)
• Intellectual_disability (1 variants)
• Microcephaly (1 variants)
• Bilateral_sensorineural_hearing_impairment (1 variants)
• Hepatomegaly (1 variants)
• Seizure (1 variants)
• Pendred_syndrome (1 variants)
• Optic_atrophy (1 variants)
• Hypoglycemia (1 variants)
• Cohen_syndrome (1 variants)
• Short_stature (1 variants)
• Hearing_loss,_autosomal_dominant_80 (1 variants)
• Hereditary_breast_ovarian_cancer_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO7A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000260.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	2	50	1192	7	1252
missense	32	192	1290	120	3	1637
nonsense	129	98	2			229
start loss		2				2
frameshift	192	115	5			312
splice donor/acceptor (+/-2bp)	51	100	1	1	1	154
Total	405	509	1348	1313	11

Highest pathogenic variant AF is 0.00040516612

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO7A	protein_coding	protein_coding	ENST00000409709	48	86975

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.61e-38	0.610	124977	0	199	125176	0.000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	1242	1.35e+3	0.918	0.0000884	14374
Missense in Polyphen		552	609.14	0.9062		6320
Synonymous	-0.749	585	562	1.04	0.0000384	4197
Loss of Function	2.89	77	110	0.702	0.00000527	1285

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00179	0.00155
Ashkenazi Jewish	0.000804	0.000795
East Asian	0.000455	0.000437
Finnish	0.00129	0.00125
European (Non-Finnish)	0.000732	0.000698
Middle Eastern	0.000455	0.000437
South Asian	0.00111	0.00108
Other	0.000845	0.000822

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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 photoreceptors. In the inner ear, plays an important role in differentiation, morphogenesis and organization of cochlear hair cell bundles. Involved in hair-cell vesicle trafficking of aminoglycosides, which are known to induce ototoxicity (By similarity). Motor 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 hearing. {ECO:0000250, ECO:0000269|PubMed:19643958, ECO:0000269|PubMed:21493626, ECO:0000269|PubMed:21687988, ECO:0000269|PubMed:21709241}.
• Disease: DISEASE: Usher syndrome 1B (USH1B) [MIM:276900]: 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. {ECO:0000269|PubMed:10094549, ECO:0000269|PubMed:10364543, ECO:0000269|PubMed:10447383, ECO:0000269|PubMed:10930322, ECO:0000269|PubMed:12112664, ECO:0000269|PubMed:15660226, ECO:0000269|PubMed:16679490, ECO:0000269|PubMed:23559863, ECO:0000269|PubMed:24831256, ECO:0000269|PubMed:25798947, ECO:0000269|PubMed:7870171, ECO:0000269|PubMed:8900236, ECO:0000269|PubMed:9002678, ECO:0000269|PubMed:9382091, ECO:0000269|PubMed:9718356}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 2 (DFNB2) [MIM:600060]: 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:28281779, ECO:0000269|PubMed:9171832, ECO:0000269|PubMed:9171833}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 11 (DFNA11) [MIM:601317]: 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. DFNA11 is characterized by onset after complete speech acquisition and subsequent gradual progression. {ECO:0000269|PubMed:15121790, ECO:0000269|PubMed:15221449, ECO:0000269|PubMed:15300860, ECO:0000269|PubMed:9354784}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling by GPCR;Signal Transduction;The canonical retinoid cycle in rods (twilight vision);G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.339

Intolerance Scores

• loftool: 0.0260
• rvis_EVS: -2.51
• rvis_percentile_EVS: 0.93

Haploinsufficiency Scores

• pHI: 0.121
• hipred: N
• hipred_score: 0.289
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.851

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myo7a
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; hearing/vestibular/ear 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); pigmentation phenotype; hematopoietic system phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: myo7aa
• Affected structure: auditory receptor cell
• Phenotype tag: abnormal
• Phenotype quality: splayed

Gene ontology

• Biological process: phagolysosome assembly;intracellular protein transport;lysosome organization;visual perception;sensory perception of sound;actin filament-based movement;cellular protein localization;eye photoreceptor cell development;mechanoreceptor differentiation;post-embryonic animal organ morphogenesis;sensory perception of light stimulus;equilibrioception;pigment granule transport;auditory receptor cell stereocilium organization
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;cytoplasm;lysosomal membrane;cytosol;microvillus;cell cortex;apical plasma membrane;myosin VII complex;photoreceptor connecting cilium;stereocilium;melanosome;synapse;stereocilium base;upper tip-link density
• Molecular function: microfilament motor activity;protein binding;calmodulin binding;ATP binding;protein domain specific binding;spectrin binding;actin-dependent ATPase activity;protein homodimerization activity;ADP binding;protein N-terminus binding;actin filament binding