GLE1: RNA Export Mediator and Motor Neuron Disease Gene
Essential regulator of mRNA export from nucleus to cytoplasm, implicated in ALS and LCCS1
Gene Information Card
| Symbol | GLE1 |
|---|---|
| Full Name | GLE1 RNA export mediator |
| Gene Type | protein-coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 2733 ncbi.nlm.nih.gov/gene/2733 |
| Ensembl ID | ENSG00000112392 |
| UniProt ID | Q53GS7 |
| OMIM ID | 603371 |
| HGNC ID | 4315 |
| Aliases | GLE1L, hGLE1, LCCS1, CMT2V |
Description
GLE1 encodes a protein that plays a critical role in the export of mRNA from the nucleus to the cytoplasm. It is a component of the TREX-2 complex and interacts with the nuclear pore complex to facilitate mRNA transport. Mutations in GLE1 are associated with autosomal recessive lethal congenital contracture syndrome 1 (LCCS1) and amyotrophic lateral sclerosis (ALS). The protein is also implicated in cell cycle regulation and stress granule formation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lethal congenital contracture syndrome 1 (LCCS1) | Loss-of-function mutations impair mRNA export, leading to defective motor neuron development and fetal akinesia. | OMIM #253310; ClinVar |
| Amyotrophic lateral sclerosis (ALS) | Missense mutations (e.g., p.Ser562Pro) disrupt GLE1 function, contributing to motor neuron degeneration. | OMIM #603371; ClinVar; PMID: 25620204 |
| Charcot-Marie-Tooth disease type 2V (CMT2V) | Heterozygous mutations in GLE1 cause axonal peripheral neuropathy. | OMIM #618531; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 15.3 | Medium |
| Testis | 20.1 | High |
| Heart | 8.7 | Low |
| Liver | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.4 | Neuronal model |
| HeLa (cervical carcinoma) | 22.1 | High expression |
| HEK293 (embryonic kidney) | 14.7 | Moderate expression |
| U-2 OS (osteosarcoma) | 16.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1684T>C (p.Ser562Pro) | Missense | Rare | Associated with ALS; disrupts mRNA export activity |
| c.43C>T (p.Arg15*) | Nonsense | Rare | Loss-of-function; causes LCCS1 |
| c.226G>A (p.Gly76Arg) | Missense | Rare | Likely pathogenic; reported in CMT2V |
| c.1045C>T (p.Arg349Trp) | Missense | Rare | Uncertain significance; ClinVar |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg15*) lead to truncated protein and loss of mRNA export function, causing LCCS1.
Gain of Function (GOF)
No clear gain-of-function mutations reported for GLE1.
Dominant Negative (DN)
Missense mutations (e.g., p.Ser562Pro) may exert dominant-negative effects by interfering with wild-type GLE1 function in ALS.
View complete mutation data：
Gene Ontology (GO)
| • mRNA export from nucleus (GO:0006406) | • nuclear pore (GO:0005643) |
| • protein binding (GO:0005515) | • RNA binding (GO:0003723) |
| • regulation of nucleocytoplasmic transport (GO:0046822) |
Pathways
• mRNA export from nucleus (Reactome: R-HSA-168276)
• TREX-2 complex pathway (Reactome: R-HSA-164952)
Protein Summary
GLE1 is a 698-amino-acid protein that localizes to the nuclear pore complex and is essential for mRNA export. It contains a coiled-coil domain and a GLE1-specific domain. The protein interacts with NUP155 and DDX19B to facilitate the release of mRNA from the nuclear basket. In the cytoplasm, GLE1 is involved in stress granule assembly. Mutations in GLE1 impair these processes, leading to motor neuron diseases.
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