### SLC28A3 Gene Overview

**Gene Symbol**: SLC28A3  
**Location**: Human chromosome 12q24.31

**Protein Summary**: 
SLC28A3 is a gene that encodes a sodium-dependent nucleoside transporter, which is selective for both pyrimidines and purines. It plays a crucial role in the homeostasis of endogenous nucleosides and is characterized by the transport of thymidine and inosine, employing a sodium-dependent mechanism with a 2:1 ratio of sodium ions to nucleosides. Moreover, it also transports uridine and various therapeutic nucleoside analogs such as gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin, and 3-deazauridine.

### 1. Associated Genes
SLC28A3 has been studied in the context of several other genes, including those involved in nucleoside metabolism and transport, such as:
- **SLC29A1**: Another nucleoside transporter, primarily responsible for the uptake of adenosine and other nucleosides.
- **SLC28A1 and SLC28A2**: Other members of the SLC28 family that have varying specificities for nucleoside transport.
- **ENTs (Equilibrative Nucleoside Transporters)**: Various genes that contribute to nucleoside transport mechanisms alongside SLC28A3.

### 2. Aging and Age-related Diseases
While direct associations between SLC28A3 and aging or age-related diseases are still under investigation, nucleoside metabolism has been linked to various cellular functions that could affect longevity and age-related conditions. Dysregulation of nucleoside transport has been implicated in:
- **Cancer**: Altered nucleoside transport can affect the efficacy of chemotherapeutic agents such as gemcitabine.
- **Neurodegenerative Diseases**: Changes in nucleoside concentrations, including adenosine, can influence neuroprotective pathways.
- **Cardiovascular Diseases**: SLC28A3 function might be linked to heart health through its role in nucleoside signaling, with implications for age-related cardiac conditions.

### 3. Known Drug Interactions
SLC28A3 is known to interact with several drugs and drug classes, including:
- **Nucleoside Analog Drugs**:
  - **Gemcitabine**: An anticancer agent used in treating various malignancies.
  - **Zidovudine (AZT)**: An antiretroviral medication used in HIV treatment.
  - **Ribavirin**: An antiviral medication used for hepatitis C and other viral infections.
  - **3-deazauridine**: A chemotherapeutic agent.
  
Additionally, any drug designed to mimic or interfere with nucleoside transport might exhibit interactions with SLC28A3.

### 4. Pathways and Biological Processes
SLC28A3 is involved in several important pathways and biological processes, such as:
- **Nucleotide Metabolism**: Contributing to the salvage pathways for nucleotides, thereby influencing DNA and RNA synthesis.
- **Signal Transduction**: As nucleosides can act as signaling molecules (e.g., adenosine signaling pathways).
- **Cell Proliferation and Survival**: By modulating nucleoside availability, SLC28A3 can impact cellular proliferation and apoptotic pathways.

In summary, SLC28A3 is a vital gene in nucleoside transport and metabolism, with implications in drug response, potential links to aging and disease, and involvement in critical biological processes. Further investigation is necessary to elucidate its precise roles in health and disease.