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EOGT
EGF domain specific O-linked N-acetylglucosamine transferase
The EOGT gene provides instructions for a protein that modifies other proteins, influencing various cellular processes and development. The EOGT gene codes for an enzyme called EGF domain specific O-linked N-acetylglucosamine transferase.
EOGT is located on the short (p) arm of chromosome 3, at band 3p14.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The EOGT gene, also known by other names such as AER61 or AOS4, contains the genetic blueprint for a protein involved in protein modification. This modification, known as O-GlcNAcylation, is important for regulating protein function and stability within cells. Alterations in the EOGT gene have been linked to developmental disorders, including Adams-Oliver syndrome, which affects skin and limb development.
What the gene does
The EOGT gene produces an enzyme responsible for a specific type of protein modification. This enzyme transfers an N-acetylglucosamine molecule onto other proteins, a process termed O-GlcNAc modification. This alteration can impact the stability of the modified proteins and is thought to regulate several fundamental cellular activities, such as intracellular signalling and the initial steps of protein synthesis from genetic instructions. While the full range of proteins modified by EOGT is still being understood, research suggests that Notch proteins may be targets. Notch proteins are key players in signalling pathways that are essential for the proper development of various tissues throughout the body, including bone, heart, liver, muscles, and blood cells.
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Chromosome location
The EOGT gene is situated on chromosome 3. Specifically, its location is mapped to band 3p14.1. This precise genomic address helps in understanding its position within the human genome.
Protein structure
The EOGT protein consists of 527 amino acids. It contains specific regions that are crucial for its function and cellular handling. A motif located at amino acids 295-297 is required for optimal activity of the enzyme. Additionally, a motif found at amino acids 524-527 prevents the protein from being secreted from the endoplasmic reticulum, ensuring its proper localisation within the cell.
Key variants
Variations within the EOGT gene can lead to changes in the protein it produces, potentially affecting its function. These changes can range from small alterations to larger structural variations, which may impact the gene's ability to properly modify other proteins. The clinical significance of many of these variants is an ongoing area of research.
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.1074del | p.Gly359fs | Pathogenic/Likely pathogenic | ★★☆☆ | Adams-Oliver syndrome 4 |
c.1335-1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | EOGT-related disorder |
c.311+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | EOGT-related disorder |
c.621-2A>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Adams-Oliver syndrome 4 |
c.78_81del | p.His27fs | Pathogenic/Likely pathogenic | ★★☆☆ | Adams-Oliver syndrome 4 |
g.(?_69058895)_(69061253_?)del | - | Pathogenic | ★☆☆☆ | Adams-Oliver syndrome 4 |
c.1234C>T | p.Gln412Ter | Pathogenic | ★☆☆☆ | Adams-Oliver syndrome 4 |
c.196_199del | p.Leu66fs | Pathogenic | ★☆☆☆ | Adams-Oliver syndrome 4 |
c.404G>A | p.Cys135Tyr | Pathogenic | ★☆☆☆ | Adams-Oliver syndrome 4 |
c.1130G>A | p.Arg377Gln | Pathogenic | - | Adams-Oliver syndrome 4 |
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 the EOGT gene have been associated with Adams-Oliver syndrome. This condition is characterised by aplasia cutis congenita, which involves areas of missing skin, typically on the scalp, and malformations affecting the hands and feet. Specific EOGT gene variants, including one common in the Arab population, have been identified in individuals with this syndrome, often leading to a shortened protein product.
No disease links recorded for this gene in our reference set.
UK clinical status
The EOGT gene is reviewed by the UK's NHS Genomic Medicine Service through PanelApp. It is listed as 'green' for several clinical panels, indicating strong evidence for its association with specific conditions. These panels include Clefting, Congenital disorders of glycosylation, DDG2P, Foetal anomalies (R21), Likely inborn error of metabolism (R98), Limb disorders, and Skeletal dysplasia (R104).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the EOGT gene?
The EOGT gene provides instructions for an enzyme that modifies other proteins by adding an N-acetylglucosamine molecule. This process, called O-GlcNAc modification, is important for regulating protein stability and various cellular processes, including signalling.
What condition is associated with variants in the EOGT gene?
Variants in the EOGT gene have been linked to Adams-Oliver syndrome. This condition is characterised by areas of missing skin, usually on the scalp, and malformations of the hands and feet.
Where is the EOGT gene located?
The EOGT gene is located on chromosome 3, specifically at the band 3p14.1 within the human genome.
References
- Ogawa M, Sawaguchi S, Kawai T. Impaired O-linked N-acetylglucosaminylation in the endoplasmic reticulum by mutated epidermal growth factor (EGF) domain-specific O-linked N-acetylglucosamine transferase found in Adams-Oliver syndrome. The Journal of biological chemistry. 2015. PMID: 25488668
- Cohen I, Silberstein E, Perez Y. Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. European journal of human genetics : EJHG. 2014. PMID: 23860037
- Shaheen R, Aglan M, Keppler-Noreuil K. Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome. American journal of human genetics. 2013. PMID: 23522784
- Sakaidani Y, Ichiyanagi N, Saito C. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1. Biochemical and biophysical research communications. 2012. PMID: 22310717
- Sakaidani Y, Nomura T, Matsuura A. O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions. Nature communications. 2011. PMID: 22158438