**TMEM199 Gene Overview**

**Gene Symbol:** TMEM199  
**Location:** Chromosome 1  
**Function:** The TMEM199 gene encodes a protein that localizes to the endoplasmic reticulum–Golgi intermediate compartment (ERGIC) and is involved in several critical biological functions, including intracellular iron homeostasis and endolysosomal acidification.

### 1. Associated Genes:
While TMEM199 is primarily associated with its own function in glycosylation disorders and iron homeostasis, it can be indirectly related to or co-expressed with several other genes involved in similar pathways or diseases, including:

- **VMA12 (yeast protein homolog)**: Similar function in vacuolar proton-transporting V-ATPase.
- **HIF1A (Hypoxia-inducible factor 1 alpha)**: Involved in oxygen sensing and metabolism in response to hypoxia, which shares a regulatory pathway with TMEM199 relating to prolyl hydroxylases.
- **ATP6V0A1 and ATP6V1A**: Subunits of the vacuolar ATPase that are functionally related to TMEM199 concerning proton transport and lysosomal function.
  
Additional genes related to congenital disorders of glycosylation may also be interconnected due to their roles in protein processing and glycosylation pathways.

### 2. Aging and Age-related Diseases:
While specific studies linking TMEM199 to aging directly may be limited, its role in intracellular iron homeostasis, lysosomal acidification, and glycosylation suggests potential involvement in age-related cellular processes. Dysfunctions in iron metabolism and lysosomal degradation pathways can contribute to various age-related diseases, including neurodegenerative disorders. Impaired glycosylation is also implicated in aging and age-associated decline in cellular function, as proper glycoprotein modifications are crucial for cellular communication and maintenance.

### 3. Drug Interactions:
Currently, there is limited information regarding specific drugs that directly target TMEM199. However, since TMEM199 is implicated in pathways related to iron metabolism and cellular stress responses, drugs that modulate these systems (like iron chelators or antioxidants) could indirectly influence the functions associated with TMEM199.

Some classes of drugs that may be relevant include:

- **Iron chelators (e.g., Deferoxamine)**: As TMEM199 is involved in iron homeostasis, alterations in iron levels may impact its function.
- **Proteasome inhibitors**: Related to HIF1A degradation processes.

### 4. Pathways and Biological Processes:
TMEM199 is involved in several key biological pathways, including:

- **Ion transport processes**: Involvement in the proton-transporting vacuolar (V)-ATPase complex conditionally associated with the endolysosome, influencing ionic homeostasis within cells.
- **Glycosylation pathways**: Since defects lead to congenital disorders of glycosylation, it contributes to processes linked to protein modification.
- **Cellular response to hypoxia**: Through regulation of HIF1A hydroxylation and degradation.
- **Lysosomal function**: Participates in lysosomal acidification and degradation processes, which are critical for cellular recycling and waste management.

Additionally, TMEM199’s role in maintaining Golgi homeostasis suggests its involvement in secretory pathways that could affect various cellular functions.