On this page
MYO7A
myosin VIIA
The MYO7A gene provides instructions for producing myosin VIIA, a protein crucial for the proper function of the inner ear and retina, with variants being a significant cause of inherited hearing and vision loss. MYO7A encodes the myosin VIIA protein, which is an unconventional myosin involved in intracellular transport and cellular structure, particularly in the hair cells of the inner ear and the retinal pigment epithelium of the eye.
MYO7A is located on the long (q) arm of chromosome 11, at band 11q13.5. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 11 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The MYO7A gene is responsible for creating the myosin VIIA protein, which belongs to a family of unconventional myosins. These proteins play a vital role in moving molecules within cells, interacting with actin to facilitate cellular movement and maintain cell shape. Myosin VIIA is particularly important in specialised cells of the inner ear and the retina, where its proper function is essential for hearing, balance, and vision.
What the gene does
Myosin VIIA functions as a motor protein that uses actin filaments as tracks for transporting other molecules within cells. In the inner ear, myosin VIIA is critical for the development and maintenance of stereocilia, which are hair-like projections that bend in response to sound waves, converting them into nerve impulses for hearing and balance. It helps in the structural integrity of these stereocilia, which are also crucial for transmitting signals from the vestibular system related to balance. In the retina, myosin VIIA is predominantly found in the retinal pigment epithelium (RPE), a layer of cells that supports and nourishes the retina. Here, it is thought to transport melanosomes (pigment sacs) and other essential molecules required for normal vision, contributing to the development and maintenance of this tissue. Dysfunction of this protein can disrupt these processes, leading to sensory impairments.
Video: Genetics 101
Chromosome location
The MYO7A gene is located on chromosome 11 at band 11q13.5. This specific chromosomal location places the gene in a region that has been linked to various inherited disorders affecting sensory functions. The gene provides instructions for a protein that is 2215 amino acids long.
Protein structure
The myosin VIIA protein features several distinct domains essential for its function. These include a Myosin motor domain (amino acids 65-741) responsible for its motor activity, and an Actin-binding region (amino acids 632-639). It also contains five IQ domains (IQ 1 to IQ 5, ranging from amino acids 745-857), a SAH region (amino acids 858-935), and two MyTH4 domains (MyTH4 1 from 1017-1253 and MyTH4 2 from 1747-1896). Additionally, the protein has two FERM domains (FERM 1 from 1258-1602 and FERM 2 from 1902-2205), and an SH3 domain (amino acids 1603-1672), all contributing to its diverse roles in intracellular processes.
Key variants
Variants within the MYO7A gene can lead to a range of inherited conditions, predominantly affecting hearing and vision. More than 200 different changes in the gene have been identified in individuals with associated health issues. These variants can alter the structure or function of the myosin VIIA protein, impairing its ability to perform its crucial roles in the inner ear and retina.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1005_1012delinsTGCCAACAGCCCCTTGCTGCCTCCCCTGATGCTGTGCCCC | p.Arg336fs | Pathogenic/Likely pathogenic | ★★☆☆ | Usher syndrome type 1B |
c.1938del | p.Phe647fs | Pathogenic/Likely pathogenic | ★★☆☆ | MYO7A-related disorder |
c.1954T>C | p.Cys652Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Usher syndrome |
c.2028C>G | p.Tyr676Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive MYO7A-related disorders |
c.2187+2_2187+8del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 2 |
c.2209G>T | p.Glu737Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 2 |
c.285+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Usher syndrome type 1 |
c.3158del | p.Pro1053fs | Pathogenic/Likely pathogenic | ★★☆☆ | MYO7A-related disorder |
c.4183del | p.Gln1395fs | Pathogenic | ★★☆☆ | Usher syndrome type 1 |
c.4397G>A | p.Trp1466Ter | Pathogenic/Likely pathogenic | ★★☆☆ | MYO7A-related disorder |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in MYO7A are a known cause of Usher syndrome type 1, specifically Usher syndrome type 1B (USH1B). This condition is characterised by a combination of profound hearing loss, progressive vision loss due to retinitis pigmentosa, and issues with balance and coordination. The gene is also associated with forms of non-syndromic hearing loss and age-related hearing loss.
- Usher syndrome type 1 Dedicated page coming soon
UK clinical status
MYO7A is recognised in the UK by the NHS Genomic Medicine Service. It is listed on the DDG2P panel as 'green', indicating strong evidence for disease causation. It is also included on the Monogenic hearing loss panel (R67) and the Retinal disorders panel (R32), both rated 'green' to signify its clinical relevance for genetic testing in these areas.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the MYO7A gene responsible for?
The MYO7A gene provides instructions for making the myosin VIIA protein, which is vital for the proper function of the inner ear and retina. It helps in intracellular transport and maintaining the structure of specialised sensory cells.
What health conditions are associated with MYO7A variants?
Variants in the MYO7A gene are primarily associated with Usher syndrome type 1B, a condition characterised by combined hearing loss, vision loss, and balance problems. It can also be linked to non-syndromic hearing loss.
Is MYO7A included in UK genetic testing programmes?
Yes, MYO7A is recognised in the UK by the NHS Genomic Medicine Service and is included on several panels, such as DDG2P, Monogenic hearing loss (R67), and Retinal disorders (R32), due to its clinical significance.
References
- Lenassi E, Saihan Z, Cipriani V. Natural history and retinal structure in patients with Usher syndrome type 1 owing to MYO7A mutation. Ophthalmology. 2014. PMID: 24199935
- Rong W, Chen X, Zhao K. Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2. PloS one. 2014. PMID: 24831256
- Williams DS, Lopes VS. The many different cellular functions of MYO7A in the retina. Biochemical Society transactions. 2011. PMID: 21936790
- Hildebrand MS, Thorne NP, Bromhead CJ. Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation. Clinical genetics. 2010. PMID: 20132242
- Riazuddin S, Nazli S, Ahmed ZM. Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function. Human mutation. 2008. PMID: 18181211
- Liu XZ, Walsh J, Mburu P. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nature genetics. 1997. PMID: 9171832
- Weil D, Küssel P, Blanchard S. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nature genetics. 1997. PMID: 9171833
- Weil D, Blanchard S, Kaplan J. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature. 1995. PMID: 7870171