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EYS
EGF-like photoreceptor maintenance factor
The EYS gene provides instructions for making a protein crucial for the development and maintenance of photoreceptor cells in the retina, playing a key role in vision. The EYS gene directs the synthesis of a large protein, EGF-like photoreceptor maintenance factor, which is primarily found in the eye.
EYS is located on the long (q) arm of chromosome 6, at band 6q12. Arm ratio per GRCh38 - banding schematic.
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Overview
The EYS gene, also known as EGF-like photoreceptor maintenance factor, is critical for vision, specifically for the proper development and ongoing health of the retina's photoreceptor cells [PMID:24713735]. These cells are responsible for converting light into electrical signals that the brain interprets as images. When the EYS gene does not function correctly due to genetic variants, it can lead to various forms of inherited retinal disease, characterised by progressive vision loss.
Studying the EYS gene helps us understand the complex mechanisms behind retinal function and the genetic basis of inherited blindness. It also aids in developing diagnostic tools and potential therapeutic strategies for these conditions.
What the gene does
The EYS gene encodes a substantial protein known as the EGF-like photoreceptor maintenance factor. This protein is predominantly expressed in the retina, specifically within the photoreceptor outer segment, a highly specialised part of the cell responsible for light detection [PMID:24713735]. The EYS protein is thought to play a structural role, contributing to the organisation and stability of the photoreceptor outer segments.
Its function is crucial for maintaining the integrity and overall health of these light-sensing cells. While the precise molecular mechanisms are still under investigation, it is believed that the EYS protein helps ensure the proper development and renewal of photoreceptors, which are constantly turning over their outer segments. Defective EYS protein can disrupt this intricate process, leading to the degeneration of photoreceptors and subsequent vision impairment.
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Chromosome location
The EYS gene is situated on the long arm of chromosome 6, specifically at position 6q12. Chromosome 6 is one of the 23 pairs of chromosomes in humans, containing a significant portion of our genetic material. The precise location of EYS helps in understanding its genetic linkage and inheritance patterns with other genes located nearby.
Protein structure
The EGF-like photoreceptor maintenance factor protein, encoded by the EYS gene, is a very large protein comprising 3165 amino acids [PMID:21727776]. It features numerous EGF-like domains, indicating potential roles in cell signalling or protein-protein interactions. These domains include EGF-like 1 (amino acids 170-212), EGF-like 2 (amino acids 213-254), EGF-like 3 (amino acids 256-292), EGF-like 4 (amino acids 332-368), EGF-like 5 (amino acids 370-406), EGF-like 6 (amino acids 567-602), and EGF-like 7 (amino acids 643-679). Additionally, the protein contains several calcium-binding EGF-like domains: EGF-like 8; calcium-binding (amino acids 681-720), EGF-like 9; calcium-binding (amino acids 733-769), EGF-like 10; calcium-binding (amino acids 771-807), EGF-like 11 (amino acids 809-847), EGF-like 12 (amino acids 849-888), EGF-like 13 (amino acids 890-926), EGF-like 14; calcium-binding (amino acids 928-964), EGF-like 15 (amino acids 966-1002), EGF-like 16; calcium-binding (amino acids 1004-1040), EGF-like 17 (amino acids 1042-1077), EGF-like 18 (amino acids 1079-1115), EGF-like 19 (amino acids 1117-1159), and EGF-like 20; calcium-binding (amino acids 1161-1197).
Key variants
Variants within the EYS gene can alter the structure or function of the EGF-like photoreceptor maintenance factor protein. These genetic changes can range from small alterations in DNA building blocks to larger deletions or duplications. The impact of a specific variant depends on its location within the gene and how it affects the resultant protein, potentially leading to a non-functional or abnormally functioning protein.
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.1057del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 25 |
c.2494C>T | p.Gln832Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 25 |
c.3215del | p.Thr1072fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 25 |
c.5868del | p.Phe1956fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 25 |
c.7269_7270dup | p.Phe2424fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 25 |
c.8159_8162del | p.Ile2720fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 25 |
GRCh37/hg19 6q12(chr6:65199723-65748082)x1 | - | Pathogenic | ★☆☆☆ | not specified |
GRCh37/hg19 6q12(chr6:65731552-65863629)x1 | - | Pathogenic | ★☆☆☆ | not specified |
g.(65532716_65596589)_(65767621_66005755)del | - | Pathogenic | ★☆☆☆ | Retinitis pigmentosa |
g.(65612394_65622376)_(65655808_65707474)del | - | Pathogenic | ★☆☆☆ | Retinitis pigmentosa |
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
Variants in the EYS gene are associated with various inherited retinal disorders, which are conditions that primarily affect the retina and can lead to progressive vision loss. These disorders often manifest as retinitis pigmentosa, a group of genetic conditions characterised by the degeneration of photoreceptor cells. The inheritance pattern for EYS-related conditions is typically autosomal recessive, meaning an individual must inherit two copies of the altered gene (one from each parent) to develop the condition.
No disease links recorded for this gene in our reference set.
UK clinical status
The EYS gene is recognised within the NHS Genomic Medicine Service and is included on the Retinal disorders testing panel, which is currently rated as green (R32). This categorisation indicates that there is strong evidence for the gene's association with these conditions, and it is routinely considered for genetic testing in the UK for individuals with suspected inherited retinal disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the EYS gene?
The EYS gene provides the instructions for making a protein called EGF-like photoreceptor maintenance factor. This protein is essential for the healthy development and ongoing maintenance of photoreceptor cells in the retina, which are crucial for vision.
What conditions are associated with variants in the EYS gene?
Variants in the EYS gene are primarily associated with various inherited retinal disorders, most notably retinitis pigmentosa. These conditions lead to the progressive degeneration of photoreceptor cells and can result in significant vision loss.
How are EYS-related conditions inherited?
Conditions linked to EYS gene variants are typically inherited in an autosomal recessive manner. This means that an individual must inherit two altered copies of the EYS gene, one from each parent, to develop the associated retinal disorder.