SLC19A3

Overview

SLC19A3 is a gene that encodes the thiamine transporter protein, which is crucial for the transport of thiamine (vitamin B1) into cells. Thiamine is an essential nutrient that plays a vital role in carbohydrate metabolism and neural function. The SLC19A3 gene is located on chromosome 2q36.3 in humans.

Function

The protein encoded by the SLC19A3 gene is a member of the solute carrier family 19, which includes other thiamine transporters such as SLC19A2. SLC19A3 specifically facilitates the uptake of thiamine into cells, particularly in tissues with high metabolic demands such as the brain and liver. This transporter is essential for maintaining adequate intracellular levels of thiamine, which is a cofactor for several enzymes involved in energy metabolism, including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.

Clinical Significance

Mutations in the SLC19A3 gene can lead to a rare neurological disorder known as Thiamine Metabolism Dysfunction Syndrome 2 (THMD2), also referred to as Biotin-Thiamine-Responsive Basal Ganglia Disease (BTBGD). This condition is characterized by recurrent episodes of encephalopathy, seizures, and movement disorders, often triggered by febrile illnesses. Early diagnosis and treatment with high doses of thiamine and biotin can significantly improve outcomes and prevent neurological deterioration.

Genetic Variants

Several pathogenic variants of the SLC19A3 gene have been identified, including missense, nonsense, and splice-site mutations. These mutations can lead to a loss of function of the thiamine transporter, resulting in reduced thiamine uptake and subsequent neurological symptoms. Genetic testing can confirm the diagnosis of THMD2 in affected individuals.

Research and Future Directions

Ongoing research is focused on understanding the precise mechanisms by which SLC19A3 mutations lead to neurological symptoms and exploring potential therapeutic interventions. Gene therapy and other novel treatment approaches are being investigated to provide more effective management options for patients with THMD2.

Also see

• Thiamine
• SLC19A2
• Vitamin B1 deficiency
• Neurological disorders