SLC5A2 Gene

The SLC5A2 gene (SLC5A2 stands for Solute Carrier Family 5 Member 2) is a protein-coding gene located on chromosome 16p11.2. Two transcript variants have been found for this gene, one of which encodes the protein while the other does not. The encoded protein is a member of the sodium-glucose cotransporter family. These are sodium-dependent glucose transport proteins.

The sodium-glucose cotransporters SGLT1(encoded by SGLT1, alsoknownas SLC5A1) and SGLT2 (encodedby SGLT2, also known as SLC5A2) are important mediators of epithelial glucose transport. While SGLT1 is responsible for most of the glucose ingested with food in the intestine, SGLT2 is responsible for most of the glucose reuptake in the tubular system of the kidney, with SGLT1 reabsorbing the rest of the filtered glucose.

Mutations in the SLC5A1 gene cause glucose/galactose malabsorption, while mutations in the SLC5A2 gene are associated with glucosuria.

Since the cloning of SGLT1 more than 30 years ago, great progress has been made in the understanding of these transporters and their suitability as drug targets. The substance phlorizin was the starting point for the development of specific inhibitors of SGLT1 and SGLT2 as well as dual SGLT1/2 inhibitors. Since the approval of the first SGLT2 inhibitor in 2013 by the US Food and Drug Administration (FDA), SGLT2 inhibitors have become a new mainstay in the treatment of type 2 diabetes mellitus. They also have beneficial effects on the cardiovascular system (including heart failure) and the kidneys.

1. Li S et al. (2019) A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature. Mol Med Rep 19:4364-4376.
2. Rieg T et al (2018) Development of SGLT1 and SGLT2 inhibitors. Diabetologia 61: 2079-2086.