### XPO1 Gene Overview

**Gene Symbol:** XPO1  
**Function:** The XPO1 gene encodes the exportin-1 protein, which is crucial for mediating the transport of proteins and RNAs out of the nucleus in a process that requires a leucine-rich nuclear export signal (NES). This protein is involved in various cellular processes including cell cycle regulation and signaling pathways.

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### 1. Genes Associated with XPO1

Aside from the genes mentioned in the summary (such as those involved in cellular processes and pathways), XPO1 has several interactions with other genes and proteins:

- **TP53:** The tumor suppressor protein p53 can affect the expression and function of XPO1, integrating the cellular response to stress.
- **NPM1:** Nucleophosmin, which is implicated in the regulation of nucleolar stress and may affect nuclear export pathways.
- **SR proteins (e.g., SRSF1):** SR proteins are involved in mRNA splicing and are also exported from the nucleus via XPO1.
- **Other exportins** (e.g. XPO5): There is functional interdependence between different exportins for the transport of various RNA species.

### 2. Age and Age-Related Diseases

XPO1 is implicated in several age-related diseases and aging processes:

- **Cancer:** Altered expression of XPO1 has been associated with various cancers (e.g., hematologic malignancies) due to its role in the nuclear export of tumor suppressor proteins like p53 and other oncogenic proteins, which can affect cellular proliferation and apoptosis.
- **Neurodegenerative Diseases:** Abnormalities in the nucleocytoplasmic transport pathway, including those mediated by XPO1, have been linked to diseases such as Alzheimer’s and Huntington's disease. Proteins such as tau can be mislocalized due to dysfunctions in XPO1.
- **Aging:** Studies suggest that the efficiency of nuclear export mechanisms may decline with age, potentially leading to the accumulation of mislocalized proteins in the nucleus, which could contribute to aging phenotypes and associated age-related pathologies.

### 3. Drugs or Drug Classes Interacting with XPO1

Several drugs target the XPO1 pathway, and inhibitors of XPO1 are currently being developed or studied:

- **Selinexor (KPT-330):** An inhibitor of XPO1 that has shown efficacy in certain hematological malignancies like multiple myeloma and acute myeloid leukemia (AML). This compound disrupts the export of proteins involved in cell growth and proliferation.
- **Other XPO1 inhibitors:** Various other inhibitors are being tested in clinical trials, as XPO1 remains a potential therapeutic target for cancer treatment.

### 4. Pathways and Biological Processes Involved with XPO1

XPO1 is involved in multiple biological pathways, including:

- **Nuclear Export Pathway:** Directly mediates nuclear export of proteins and RNAs bearing NES signals.
- **Cell Cycle Regulation:** Contributes to the localization and export of cyclins and cyclin-dependent kinase inhibitors, thereby influencing cell cycle progression.
- **Immune Response:** Involved in the export of transcription factors like NFAT and AP-1, which are significant for immune signaling.
- **RNA Processing and Transport:** Plays a critical role in the transport of various RNAs, including small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs), from their sites of synthesis to their functional locations.

XPO1 is a key regulator of cellular homeostasis and its dysregulation can lead to an array of health issues, highlighting its importance as a genetic and therapeutic target in various diseases.