SLC13A5

SLC13A5 is a tricarboxylate plasma transporter with a preference for citrate.^[5]

In 2014, by means of exome sequencing it was determined that a genetic mutation of the gene is the cause of a rare SLC13A5 Epilepsy.^[6] Mutations in SLC13A5 cause autosomal recessive epileptic encephalopathy with seizure onset in the first days of life.^[6] Those afflicted suffer from seizures, global developmental delay, movement disorder and hypotonia.

Reduced expression of homologous genes is associated with longer lifespan in Drosophila melanogaster and Caenorhabditis elegans,^[7][8] and obesity protection in laboratory mice.^[9] Increased expression is associated with type 2 diabetes and non-alcoholic fatty liver disease. A sugary diet upregulates the expression of the gene, and so does Interleukin 6 signaling.^[10]

There are four small-molecule inhibitors to SLC13A5 that have been reported from Pfizer^[11][12] and a derivative from China Pharmaceutical University,^[13] Boehringer Ingelheim and the group of Elisabeth P. Carpenter from the Centre for Medicines Discovery,^[14] and Eternygen.^[15] The Pfizer molecule is an orthosteric inhibitor that locks the protein in an inward-facing state of the reaction cycle,^[16] while the mechanism of action for other inhibitors remains unknown.