SLC13A5

Description

The SLC13A5 (solute carrier family 13 member 5) is a protein-coding gene located on chromosome 17.

SLC13A5 (Solute carrier family 13 (sodium-dependent citrate transporter), member 5), also known as the Na+/citrate cotransporter or mIndy, is a protein encoded by the SLC13A5 gene in humans. It is the mammalian homolog of the fly Indy gene. SLC13A5 is a tricarboxylate plasma transporter with a preference for citrate. Mutations in SLC13A5 cause autosomal recessive epileptic encephalopathy with seizure onset in the first days of life. Those afflicted suffer from seizures, global developmental delay, movement disorder, and hypotonia. Reduced expression of this gene is associated with longer lifespans in various organisms, including some non-human primates. Increased expression is linked to type 2 diabetes and non-alcoholic fatty liver disease. A sugary diet and Interleukin 6 signaling upregulate the expression of the gene.

SLC13A5 is a high-affinity sodium/citrate cotransporter that facilitates the entry of citrate into cells. Citrate is a crucial participant in several biochemical pathways, including energy production (Krebs cycle), fatty acid synthesis, cholesterol synthesis, glycolysis, and gluconeogenesis. The transporter utilizes a sodium-dependent mechanism, specifically recognizing the trivalent form of citrate at physiological pH. Although it can recognize succinate as a substrate, its affinity for succinate is significantly lower than for citrate. The stoichiometry likely involves 4 sodium ions for each carboxylate, regardless of the divalent or trivalent nature of the transported substrate, resulting in an electrogenic process. SLC13A5 plays a role in regulating citrate levels within the brain.

SLC13A5 is also known as DEE25, EIEE25, INDY, NACT, mIndy.

Associated Diseases

• Amelocerebrohypohidrotic syndrome
• Non-specific early-onset epileptic encephalopathy
• Epileptic encephalopathy, early infantile, 25, with amelogenesis imperfecta