TFG (gene)

TFG, also known as Thyroid transcription factor-1-interacting protein or TRK-fused gene, is a human gene located on chromosome 3q12.1. It encodes a protein that is involved in various cellular processes, including protein trafficking, vesicular transport, and the unfolded protein response (UPR).

The TFG protein contains several domains, including an N-terminal coiled-coil domain, a central region with multiple phosphorylation sites, and a C-terminal region that interacts with other proteins. It functions as a scaffold protein, interacting with various proteins to regulate their function and localization.

TFG plays a crucial role in endoplasmic reticulum (ER) homeostasis and the response to ER stress. It is involved in the formation and maintenance of the ER exit sites (ERES), which are specialized regions of the ER membrane where transport vesicles bud off. It interacts with components of the COPII coat complex, which mediates the transport of proteins from the ER to the Golgi apparatus.

Mutations in the TFG gene have been implicated in several diseases, including hereditary sensory and autonomic neuropathy type 1E (HSAN1E), also known as distal hereditary motor neuropathy type V (dHMN-V). HSAN1E is a rare neurodegenerative disorder characterized by progressive sensory loss, autonomic dysfunction, and motor weakness. These mutations typically affect the coiled-coil domain of the TFG protein, disrupting its ability to interact with other proteins and impairing ER function.

TFG has also been shown to be involved in cancer. Chromosomal translocations involving the TFG gene have been identified in some cases of papillary thyroid carcinoma (PTC), leading to the formation of fusion proteins that can contribute to tumorigenesis. The most common fusion partner is NTRK1, resulting in a constitutively active tyrosine kinase that promotes cell proliferation and survival.

Research continues to explore the precise mechanisms by which TFG contributes to cellular function and its role in various diseases. Understanding its function and regulation is crucial for developing potential therapeutic strategies for diseases associated with TFG dysfunction.