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EOGT
EGF domain specific O-linked N-acetylglucosamine transferase
The EOGT gene provides instructions for creating an enzyme crucial for modifying other proteins, a process that influences cell signalling and development. EOGT encodes 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 is responsible for producing the enzyme EGF domain specific O-linked N-acetylglucosamine transferase. This enzyme plays a role in post-translational modification, specifically by attaching N-acetylglucosamine (GlcNAc) to other proteins. This type of modification, known as O-GlcNAcylation, can influence how proteins function and interact within cells, impacting various biological pathways.
Changes in the EOGT gene have been linked to certain inherited conditions, highlighting its importance in normal human development and cellular regulation.
What the gene does
The EOGT gene directs the synthesis of an enzyme that performs O-GlcNAc modification. This involves transferring an N-acetylglucosamine molecule to specific target proteins. This modification can alter the stability of proteins and regulate several cellular activities, including cell signalling and the initial steps of gene transcription.
While the full range of proteins modified by EOGT remains under investigation, research suggests that Notch proteins may be among its targets. Notch proteins are integral to signalling pathways that are vital for the development of numerous tissues throughout the body, such as bones, the heart, liver, muscles, and blood cells. Therefore, EOGT's activity can indirectly influence these developmental processes.
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Chromosome location
The EOGT gene is situated on the short arm of chromosome 3 at position 14.1, a location denoted as 3p14.1. This specific genomic address helps in identifying its precise position within the human genome.
Protein structure
The EOGT protein is composed of 527 amino acids. It contains specific regions that are critical for its function and cellular localisation. A motif located between amino acids 295 and 297 is required for the enzyme's optimal activity. Additionally, a motif found at amino acids 524-527 prevents the protein from being secreted from the endoplasmic reticulum, ensuring it remains within the cell to perform its functions.
Key variants
Genetic variations, or variants, within the EOGT gene can alter the function of the encoded enzyme. These changes can range from single base-pair substitutions to larger deletions or insertions, potentially affecting protein production, stability, or activity. The impact of such variants depends on their specific nature and location within the gene.
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.621-2A>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Adams-Oliver syndrome 4 |
c.78_81del | p.His27fs | 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.1335-1G>A | - | Pathogenic | ★☆☆☆ | Adams-Oliver syndrome 4 |
c.196_199del | p.Leu66fs | Pathogenic | ★☆☆☆ | Adams-Oliver syndrome 4 |
c.311+1G>T | - | 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
Variants in the EOGT gene have been associated with Adams-Oliver syndrome. This condition is characterised by specific developmental abnormalities, notably aplasia cutis congenita (areas of missing skin, typically on the scalp) and malformations of the hands and feet. The severity and specific manifestations can vary among individuals.
No disease links recorded for this gene in our reference set.
UK clinical status
The EOGT gene is included on several NHS Genomic Medicine Service (GMS) approved panels within the UK. It is categorised as 'green' (evidence for a gene-disease association) on panels for 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 primary function of the EOGT gene?
The EOGT gene provides instructions for making an enzyme that modifies other proteins by attaching N-acetylglucosamine molecules. This modification influences protein stability and cellular processes like signalling and gene transcription.
Which condition is associated with variants in the EOGT gene?
Variants in the EOGT gene are associated with Adams-Oliver syndrome. This condition typically presents with aplasia cutis congenita (missing skin areas) and malformations of the hands and feet.
Where is the EOGT gene located in the human genome?
The EOGT gene is located on chromosome 3, specifically on the short arm at position 14.1, which is denoted as 3p14.1.
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