SLC5A1 Gene: Function, Mutations, and Associated Diseases | SGLT1

SLC5A1 encodes the sodium/glucose cotransporter 1 (SGLT1), a member of the solute carrier family 5. SGLT1 is primarily expressed in the brush border of intestinal epithelial cells and renal proximal tubules, where it mediates active transport of glucose and galactose across cell membranes coupled with sodium. This transporter is critical for dietary sugar absorption and renal glucose reabsorption. Mutations in SLC5A1 cause glucose-galactose malabsorption, a rare autosomal recessive disorder characterized by severe diarrhea in infancy. SGLT1 also plays roles in other tissues and has been implicated in various physiological and pathological processes.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Carbohydrate digestion and absorption (KEGG hsa04973)

• Sodium/glucose cotransporter activity in renal reabsorption

• Transport of glucose and other sugars (Reactome)

SGLT1 is a 664-amino acid integral membrane protein with 14 transmembrane helices. It couples the downhill influx of sodium to the uphill transport of glucose or galactose, with a stoichiometry of 2 Na+:1 sugar. The protein is heavily glycosylated and localized to the apical membrane of enterocytes and renal proximal tubule cells. Its structure includes a core domain for sugar binding and a gate domain for conformational changes. SGLT1 is also expressed in other tissues, where it may have non-transport functions, such as in glucose sensing. The protein is a target for pharmacological inhibition in diabetes (e.g., SGLT inhibitors), though SGLT2 is the primary target in the kidney.