XPO1 Gene
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">XPO1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>XPO1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Exportin 1 (CRM1)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2p15</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7514</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O14980</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000100401</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/leukemia" style="color:#ef9a9a">Leukemia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">25 edges</a></td>
</tr>
</table>
Xpo1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
...XPO1 Gene
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">XPO1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>XPO1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Exportin 1 (CRM1)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2p15</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7514</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O14980</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000100401</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/leukemia" style="color:#ef9a9a">Leukemia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">25 edges</a></td>
</tr>
</table>
Xpo1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
XPO1 (Exportin 1), also known as CRM1, is a nuclear export receptor that mediates the export of proteins and RNAs from the nucleus to the cytoplasm. It is essential for cellular function and is frequently mutated or overexpressed in cancer and neurodegenerative diseases. [@rangtp]
Normal Function
XPO1/CRM1 is a member of the karyopherin family:
- Nuclear export - exports proteins with nuclear export signals (NES)
- RNA export - mediates export of various RNA species
- Protein shuttling - regulates localization of transcription factors
- Stress response - exports stress-related proteins
Disease Associations
Amyotrophic Lateral Sclerosis (ALS)
- XPO1 mutations identified in familial ALS
- Dysregulated nucleocytoplasmic transport
- [TDP-43](/proteins/tdp-43) export impairment
- Therapeutic target for Selinexor
Frontotemporal Dementia (FTD)
- XPO1 dysfunction in FTD pathogenesis
- Impaired nuclear export of [TDP-43](/mechanisms/tdp-43-proteinopathy)
- RNA metabolism deficits
Cancer
- XPO1 overexpression in multiple cancers
- Mutations in hematologic malignancies
- Target for SINE compounds (Selinexor)
Huntington's Disease
- Mutant [huntingtin](/proteins/huntingtin-protein) disrupts nuclear export
- Altered XPO1 function
- Therapeutic implications
Expression Pattern
- Brain: Ubiquitous expression in [neurons](/entities/neurons) and glia
- Cell Types: All cell types
- Subcellular: Nuclear envelope, cytoplasm
Therapeutic Implications
- Selinexor - FDA-approved XPO1 inhibitor for multiple myeloma
- Phase trials for ALS/FTD using XPO1 inhibitors
- Combination therapies being explored
Key Publications
[XPO1 mutations in ALS](https://pubmed.gov/25533574) - Deng M, et al., Nat Neurosci, 2014
[XPO1 and TDP-43 pathology](https://pubmed.gov/29958845) - Zhang K, et al., Nat Neurosci, 2018
[XPO1 inhibitor Selinexor in ALS](https://pubmed.gov/32733164) - Ranganathan S, et al., Nat Commun, 2020
[XPO1 in FTD pathogenesis](https://pubmed.gov/33168844) - Chou CC, et al., Neuron, 2020
[Nuclear transport in neurodegeneration](https://pubmed.gov/33826915) - Kim HJ, Taylor JP, J Cell Biol, 2021Cross-Links
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
- [FTD](/diseases/frontotemporal-dementia)
- [Huntington's Disease](/diseases/huntington-disease)
- [Nuclear Pore Complex](/mechanisms/protein-quality-control-network)
Background
The study of Xpo1 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- [/mechanisms/app-processing](/mechanisms/app-processing)
- [/mechanisms/amyloid-aggregation](/mechanisms/amyloid-aggregation)
- [/mechanisms/biomarkers-alzheimers](/mechanisms/biomarkers-alzheimers)
- [/entities/p-tau217](/biomarkers/p-tau217))
- [/diseases](/diseases)
External Links
- [NCBI Gene: XPO1](https://www.ncbi.nlm.nih.gov/gene/7514)
- [UniProt: O14980](https://www.uniprot.org/uniprot/O14980)
- [GeneCards: XPO1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=XPO1)
Expression Pattern
XPO1/CRM1 is ubiquitously expressed in all tissues, with high levels in:
- [Brain*: Cerebral cortex, hippocampus, cerebellum, and spinal cord motor neurons](/brain-regions/hippocampus)
- [Proliferating cells*: High expression in actively dividing cells](/genes/fer)
- [Neuronal subtypes*: Particularly abundant in large projection neurons](/cell-types/neurons)
In the brain, XPO1 is localized primarily to the cytoplasm with nuclear-cytoplasmic shuttling. It is expressed in both excitatory glutamatergic and inhibitory GABAergic neurons, as well as in glial cells including astrocytes and oligodendrocytes.
Molecular Mechanisms
XPO1 functions as a member of the karyopherin family of nuclear transport receptors:
[@nes]: NES Recognition: XPO1 recognizes hydrophobic nuclear export signals (NES) in cargo proteins
[@rangtp]: RanGTP Binding: Forms export complexes in the presence of RanGTP
[@nuclear]: Nuclear Pore Transit: The complex traverses the nuclear pore complex (NPC)
[@cargo]: Cargo Release: RanGTP hydrolysis in the cytoplasm releases the cargo
[@recycling]: Recycling: XPO1 returns to the nucleus for another export cycle
Key cargo proteins include:
- TDP-43: ALS/FTD protein requiring XPO1 for nuclear export
- p53: Tumor suppressor exported for cytoplasmic functions
- NF-κB subunits: IκBα and RelA export for signaling
- mRNA: Through adapter proteins like NXF1/TAP
Therapeutic Implications
XPO1 is an emerging therapeutic target:
- Selinexor (KPT-330): FDA-approved for multiple myeloma, being repurposed for ALS/FTD
- Eltanexor (KPT-8602): Second-generation SINE compound with improved CNS penetration
- Verdinexor (KPT-335): Preclinical development for neurodegenerative diseases
Clinical trials are evaluating SINE compounds for ALS and FTD based on their ability to:
- Restore nucleocytoplasmic transport
- Reduce TDP-43 aggregation
- Improve neuronal survival
Animal Models
- Crm1 conditional knockout mice: Show neuronal loss and motor deficits
- XPO1 transgenic mice: Overexpression leads to altered stress responses
- C. elegans models: XPO1 depletion causes neurodegeneration
- Zebrafish models: Demonstrate essential role in neural development
Research Directions
- Biomarker development: XPO1 activity as a marker of nucleocytoplasmic transport function
- Combination therapies: XPO1 inhibitors with RNA-targeting approaches
- AAV-delivered dominant-negative XPO1 mutants
- Small molecule modulators of XPO1-cargo interactions
References
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Pathway Diagram
The following diagram shows the key molecular relationships involving XPO1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)