MYO15A

Official Full Name

myosin XVA

Organism

Homo sapiens

Gene ID

51168

Background

This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

Synonyms

DFNB3; MYO15

Cat.No.	Product Name	Price
CSC-DC010018	Panoply™ Human MYO15A Knockdown Stable Cell Line	Inquiry
CSC-SC010018	Panoply™ Human MYO15A Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
LV18973L	human MYO15A (NM_016239) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH212519	shRNA set against Mouse Myo15(NM_010862.2)	Inquiry
SHH348080	shRNA set against Mouse Myo15 (NM_182698.2)	Inquiry
SHH348088	shRNA set against Human MYO15A (NM_016239.3)	Inquiry

Cat.No.	Product Name	Price
CDCR275714	Mouse Myo15 ORF Clone(NM_182698.2)	Inquiry
CDFL008066	Mouse Myo15 cDNA Clone(NM_182698.2)	Inquiry
MiUTR1H-06591	MYO15A miRNA 3'UTR clone	Inquiry
MiUTR1M-07455	MYO15 miRNA 3'UTR clone	Inquiry
MiUTR1M-07456	MYO15 miRNA 3'UTR clone	Inquiry
CDCB182168	Rabbit MYO15A ORF clone (XM_008250366.1)	Inquiry
CDCH391153	Mouse Myo15 ORF clone(NM_010862.2)	Inquiry
CDCH391155	Mouse Myo15 ORF clone(NM_001103171.1)	Inquiry
CDCH391156	Human MYO15A ORF clone(NM_016239.3)	Inquiry

Detailed Information

The MYO15A gene is located at the DFNB3 locus. The researchers first discovered the DFNB3 locus for genome-wide screening of deaf patients from Indonesia. The study found that mouse shaker-2 syndrome is consistent with the localization of DFNB3 deafness in this conservative region, so it is speculated whether this mutation can be found in mice with a phenotype of shaker-2 syndrome and reveals the cause of the human DFNB3 deafness. Mutation of MYO15A gene is one of the causative causes of autosomal recessive non-combination syndrome.

The longest transcript encoded by the MYO15A gene includes 35390 amino acid residues (molecular weight 365 KDa), of which exon 2 encodes an extended N-terminus. This is followed by the motor domain of the head, including: ATP and myosin junction sites, type I and type II spirals, converter, subsequent spiral, SH3 helix, SH1/SH2 helix and a converter domain. The encoded myosin XVa can be divided into two subtypes based on the presence or absence of an N-terminal region encoded by exon 2 of the MYO15A gene in its head: myosin XVa-subtype 1 exists by exon 2 In the encoded N-terminal region, myosin XVa-subtype 2 has no N-terminal region.

Figure 1. The locations of MYO15A variants. (Chang, M. Y., et al. 2018)

MYO15A Mutation Related Mouse Model

Shaker2 (sh2) was first reported in 1928 as a progeny of rats exposed to X-ray ionizing radiation, showing poor response to sound, abnormal shaking and rotational behavior. Sh2 mouse Myo15a is located on chromosome 11 and is homologous to human DFNB3 at 17 pl 1.2. After injecting bacterial artificial chromosome BAC425p24 (140-kb t) (BACs) containing wild-type MYO15A into the fertilized eggs of homozygous mutant sh2 mice, the hearing power of sh2 mice recovered. The offspring of the breeding line carried BAC425p2 and the hearing was normal. It is through BAC that the hearing of sh2 mice can be restored, and MYO15A encoding unconventional myosin is finally identified.

Study on The Correlation between MYO15A Mutant Genotype and Hearing Phenotype

Studies have shown that the N'-end mutation encoded by exon 2 of MYO15A (p.G1112fsX1124) results in a light hearing phenotype with low frequency residual hearing. The study concluded that the hearing loss phenotype of MYO15A mutation patients is closely related to the region in which the gene mutation is located. Myosin XVa is divided into two subtypes, subtype 1 has an N-terminal region encoded by exon 2, and subtype 2 has no N-terminal region. Studies have shown that mutations in the N-terminal region result in abnormal myosin isoform 1 and the hearing phenotype is non-severe severe sensorineural hearing loss with residual hearing, such as reported MYO15A (p.Arg1112ValfsX1124), MYO15A (p .Tyr289X), MYO15A (p. Glu396Argfs*36) and MYO15A (p.Ser1176Valfs*14), etc. The hearing phenotypes that occur in the N-terminal region are low-frequency regions with residual hearing and sensorineural hearing loss.

Mutations in the N-terminal region of MYO15A exon 2 coding are associated with a non-severe hearing phenotype. The results of studies involving mutations in other regions and severe auditory phenotypes provide molecular genetic evidence for precision medical care in patients with MYO15A mutations. The degree of hearing loss can be predicted based on the different regions in which the MYO15A mutation is located. For mutations located in the N-terminal domain encoded by exon 2, low-frequency residual hearing needs to be considered, and low-frequency residual hearing is preserved as much as possible in cochlear implantation. Electroacoustic stimulation (EAS) was chosen as the best choice for hearing rehabilitation after surgery. MYO15A mutations encoding other domains require early consideration of cochlear implants and speech rehabilitation training.

References:

Chang, M. Y. , Lee, C. , Han, J. H. , Kim, M. Y. , Park, H. R. , & Kim, N. , et al. (2018). Expansion of phenotypic spectrum of myo15a pathogenic variants to include postlingual onset of progressive partial deafness. BMC Medical Genetics, 19(1), 29.
Hong, X. , Xiangjun, H. , Yi, G. , Pengzhi, H. , Guangxiang, H. , & Xiong, D. , et al. (2015). Identification of a novel myo15a mutation in a chinese family with autosomal recessive nonsyndromic hearing loss. PLOS ONE, 10(8), e0136306-.
Di, M. , Shanshan, S. , Hui, G. , Hui, G. , Yumei, L. , & Yuhua, H. , et al. (2018). A novel nonsense mutation in myo15a is associated with non-syndromic hearing loss: a case report. BMC Medical Genetics, 19(1), 133-.

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