MYO15A

myosin XVA, the group of FERM domain containing|Myosin heavy chains, class XV

Basic information

Region (hg38): 17:18108756-18179802

Previous symbols: [ "DFNB3", "MYO15" ]

Links

ENSG00000091536

∙ NCBI:51168 ∙ OMIM:602666 ∙ HGNC:7594 ∙ Uniprot:Q9UKN7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive nonsyndromic hearing loss 3 (Strong), mode of inheritance: AR
hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 3 (Definitive), mode of inheritance: AR
nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 3	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	17851452; 23226338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO15A gene.

not_provided (2818 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_3 (834 variants)
Inborn_genetic_diseases (577 variants)
not_specified (353 variants)
MYO15A-related_disorder (97 variants)
Rare_genetic_deafness (50 variants)
Hearing_impairment (27 variants)
Nonsyndromic_genetic_hearing_loss (16 variants)
Hearing_loss,_autosomal_recessive (16 variants)
Monogenic_hearing_loss (12 variants)
Childhood_onset_hearing_loss (6 variants)
Ear_malformation (6 variants)
Congenital_sensorineural_hearing_impairment (3 variants)
Intellectual_disability (2 variants)
Deafness,_with_smith-magenis_syndrome (1 variants)
Carney_complex,_type_1 (1 variants)
Alport_syndrome (1 variants)
Sensorineural_hearing_loss_disorder (1 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_9 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO15A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016239.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	2 clinvar	4 clinvar	24 clinvar	1038 clinvar	7 clinvar	1075
missense	24 clinvar	138 clinvar	933 clinvar	216 clinvar	6 clinvar	1317
nonsense	109 clinvar	43 clinvar	1 clinvar	1 clinvar		154
start loss						0
frameshift	194 clinvar	100 clinvar	1 clinvar			295
splice donor/acceptor (+/-2bp)	53 clinvar	79 clinvar	4 clinvar	1 clinvar		137
Total	382	364	963	1256	13

Highest pathogenic variant AF is 0.00019952585

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO15A	protein_coding	protein_coding	ENST00000205890	65	71097

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124453	1	468	124922	0.00188

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.646	1975	2.06e+3	0.960	0.000147	22488
Missense in Polyphen		138	152.41	0.90545		1301
Synonymous	1.60	826	886	0.932	0.0000662	7280
Loss of Function	3.78	116	169	0.686	0.00000936	1848

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00371	0.00367
Ashkenazi Jewish	0.000600	0.000596
East Asian	0.00400	0.00384
Finnish	0.000559	0.000557
European (Non-Finnish)	0.00187	0.00182
Middle Eastern	0.00400	0.00384
South Asian	0.00223	0.00193
Other	0.00217	0.00214

dbNSFP

Source: dbNSFP

Function: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Required for the arrangement of stereocilia in mature hair bundles (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.160

Intolerance Scores

loftool: 0.0478
rvis_EVS: -1.26
rvis_percentile_EVS: 5.35

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.620

Gene Damage Prediction

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

Gene ontology

Biological process: sensory perception of sound;locomotory behavior;inner ear morphogenesis
Cellular component: cytoplasm;myosin complex;stereocilium;extracellular exosome
Molecular function: motor activity;actin binding;calmodulin binding;ATP binding