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
• autosomal recessive nonsyndromic hearing loss 3 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 3 (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 (2756 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_3 (817 variants)
• Inborn_genetic_diseases (528 variants)
• not_specified (339 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)
• Childhood_onset_hearing_loss (6 variants)
• Ear_malformation (6 variants)
• Monogenic_hearing_loss (4 variants)
• Congenital_sensorineural_hearing_impairment (3 variants)
• Intellectual_disability (2 variants)
• Deafness,_with_smith-magenis_syndrome (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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	4	22	1019	7	1053
missense	25	135	876	212	7	1255
nonsense	108	42	2			152
start loss						0
frameshift	190	96	1			287
splice donor/acceptor (+/-2bp)	52	79	1	1		133
Total	376	356	902	1232	14

Highest pathogenic variant AF is 0.00019952585

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
1.25e-56	0.910	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

Haploinsufficiency Scores

• pHI: 0.381
• ghis: 0.503

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

Mouse Genome Informatics

• Gene name: Myo15
• Phenotype: vision/eye 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

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