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GLE1
GLE1 RNA export mediator
The GLE1 gene provides instructions for making a protein crucial for transporting messenger RNA (mRNA) from the cell's nucleus to the cytoplasm, a fundamental step in protein synthesis. The GLE1 gene is vital for cellular function, specifically in regulating what leaves the nucleus.
GLE1 is located on the long (q) arm of chromosome 9, at band 9q34.11. Arm ratio per GRCh38 - banding schematic.
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Overview
The GLE1 gene, also known as GLE1 RNA export mediator, encodes a protein that is an essential component of the nuclear pore complex (NPC). This complex acts as a selective gate, controlling the movement of molecules between the nucleus and the cytoplasm. The GLE1 protein is primarily involved in the export of messenger RNA (mRNA) from the nucleus, a critical process for gene expression and protein production.
What the gene does
The protein produced by the GLE1 gene is an essential component of the mRNA export pathway. It works in conjunction with other proteins to ensure that mature mRNA molecules are correctly transported from the nucleus, where they are transcribed, to the cytoplasm, where they are translated into proteins. This regulated export mechanism is vital for maintaining cellular homeostasis and proper development. The GLE1 protein interacts specifically with NUP155 and NUP42, other proteins involved in nuclear pore function, facilitating its role in guiding mRNA through the nuclear pore complex.
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Chromosome location
The GLE1 gene is situated on chromosome 9 at band 9q34.11. This specific location indicates its position on the long (q) arm of chromosome 9. Understanding the chromosomal location helps in mapping genes and investigating their association with inherited conditions.
Protein structure
The GLE1 protein consists of 698 amino acids and features several distinct regions critical for its function. An interaction with NUP155 region is found at amino acids 1-29. There are also disordered regions located at amino acids 63-121 and 332-375. Two distinct coiled coil domains are present, one spanning amino acids 151-277 and another from amino acids 305-356. A significant region from amino acids 444-483 mediates the shuttling between the nucleus and the cytoplasm, and an interaction with NUP42 region is found at amino acids 656-698.
Key variants
Variants within the GLE1 gene can alter the structure or function of the GLE1 protein, potentially impairing its role in mRNA export. These genetic changes can range from small alterations in the DNA sequence to larger deletions or duplications. The specific effect of a variant depends on its location and how it impacts the protein's ability to participate in nuclear transport.
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.1006_1007del | p.Lys336fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal congenital contractural syndrome Finnish type |
c.1054C>T | p.Gln352Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal congenital contractural syndrome Finnish type |
c.1092dup | p.Ala365fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.112G>T | p.Glu38Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal congenital contractural syndrome Finnish type |
c.1135del | p.Gln379fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal congenital contractural syndrome Finnish type |
c.1203_1204del | p.Leu402fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal arthrogryposis-anterior horn cell disease syndrome |
c.153G>A | p.Trp51Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal congenital contractural syndrome Finnish type |
c.357_364del | p.Gln121fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal arthrogryposis-anterior horn cell disease syndrome |
c.450G>A | p.Trp150Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal arthrogryposis-anterior horn cell disease syndrome |
c.456_472dup | p.Val158fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal congenital contracture syndrome 1 |
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 GLE1 gene have been linked to severe neurological and developmental disorders, often presenting with symptoms such as arthrogryposis. These conditions arise from the disruption of the crucial mRNA export process, which is essential for normal cellular development and function, particularly in the brain and nervous system.
No disease links recorded for this gene in our reference set.
UK clinical status
The GLE1 gene is recognised in the UK, with its inclusion on several NHS England Genomic Medicine Service clinical panels. It is listed as 'green' for Arthrogryposis (R83), DDG2P (Developmental Disorders Gene Panel), and Foetal anomalies (R21), signifying its established role in these conditions and its routine consideration in diagnostic testing within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the GLE1 gene?
The GLE1 gene encodes a protein that facilitates the transport of messenger RNA (mRNA) from the cell's nucleus to the cytoplasm, which is essential for protein synthesis.
Which conditions are associated with variants in the GLE1 gene?
Variants in the GLE1 gene are associated with severe developmental and neurological conditions, including arthrogryposis.
How is the GLE1 gene status determined in the UK?
In the UK, the GLE1 gene is assessed through NHS England Genomic Medicine Service clinical panels, specifically for conditions like arthrogryposis, developmental disorders, and foetal anomalies.