### NUDT15 Gene Overview

**Gene Symbol:** NUDT15  
**Location:** Human Chromosome 10

**Function:**  
NUDT15 encodes a Nudix hydrolase enzyme that plays a critical role in nucleotide metabolism, specifically in the hydrolysis of nucleoside triphosphates and di- and tri-phosphates, helping to prevent the incorporation of oxidatively damaged nucleotides into DNA. This enzyme is particularly involved in the metabolism of thiopurine drugs used in cancer therapy and autoimmune diseases.

### 1. Associated Genes
NUDT15 is known to have interactions or associations with several other genes involved in thiopurine metabolism and DNA repair, including:

- **TPMT (Thyopurine S-methyltransferase):** Involved in the metabolism of thiopurine drugs.
- **MGMT:** DNA repair gene that may interact with pathways involving oxidative damage.
- **MTHFR (Methylenetetrahydrofolate reductase):** Related in the metabolic pathways that may influence thiopurine metabolism.

### 2. Aging and Age-Related Diseases
Research has indicated that mutations in NUDT15 are linked to susceptibility to various hematological conditions, particularly in patients undergoing thiopurine therapy, which is often given for autoimmune conditions that may be more common in older populations. Additionally, oxidative stress and DNA damage repair mechanisms, in which NUDT15 is involved, are critical processes that have implications for aging and age-related diseases.

### 3. Drug Interactions
NUDT15 is particularly notable for its role in thiopurine drug metabolism. Key drugs and drug classes known to interact with this gene include:

- **Thiopurine Drugs:** Such as azathioprine, mercaptopurine, and thioguanine. Variants of NUDT15 can lead to enhanced toxicity and adverse reactions when these drugs are administered.
  
The NUDT15 gene is not directly linked to many other drug classes but has significant implications in the pharmacogenomics of drugs that require thiopurine metabolism.

### 4. Pathways and Biological Processes
NUDT15 is involved in several critical pathways and biological processes:

- **Nucleotide Metabolism:** Hydrolysis of nucleotides is crucial for DNA and RNA synthesis and repair.
- **Thiopurine Metabolism:** Hydrolyzes thiopurine derivatives for proper metabolism and toxicity regulation.
- **DNA Repair Mechanism:** May play a role in the repair of oxidatively damaged nucleotides to maintain genomic stability.
- **Cell Cycle Regulation:** NUDT15 may influence the stabilization and activity of cell cycle proteins, including PCNA (proliferating cell nuclear antigen).
- **RNA Decapping:** Exhibits decapping activity towards specific RNA molecules, contributing to RNA turnover and regulation of gene expression.

### Summary
The NUDT15 gene encodes a crucial enzyme that is integral to nucleotide metabolism, particularly in the context of thiopurine drug metabolism and oxidative stress response. Its interactions with other genes, its role in disease susceptibility, particularly in older adults, and its involvement in DNA repair and cell cycle regulation highlight its importance in both pharmacogenomics and overall genomic stability.