solute carrier family 2 member 9
The SLC2A9 gene provides instructions for making a protein called glucose transporter 9 (GLUT9). This protein is found mainly in the kidneys, specifically in structures called proximal tubules. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete unneeded substances into the urine. Within the proximal tubules, the GLUT9 protein helps transport a substance called uric acid. Uric acid is a byproduct of certain normal chemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, having too much uric acid in the body is toxic, so excess uric acid is removed from the body in urine. The GLUT9 protein helps reabsorb uric acid (or a similar version of this substance called urate) into the bloodstream or release it into the urine, depending on the body's needs. Most uric acid that is filtered through the kidneys is reabsorbed into the bloodstream; about 10 percent is released into urine.
The GLUT9 protein also plays a role in reabsorbing and excreting the simple sugar glucose.
At least 13 mutations in the SLC2A9 gene have been found to cause renal hypouricemia. This condition results in a reduced amount of uric acid in the blood. Renal hypouricemia often does not cause any health problems but can lead to pain and nausea after exercise, kidney stones, or blood in the urine (hematuria). Most of the mutations that cause renal hypouricemia replace single protein building blocks (amino acids) in the GLUT9 protein and severely reduce or eliminate the protein's ability to reabsorb uric acid in the bloodstream. As a result, an excessive amount of uric acid is lost through the urine. While it is not clear how these changes in uric acid levels lead to the signs and symptoms of renal hypouricemia, it is likely that the loss of uric acid's antioxidant properties in combination with the increase in uric acid passing through the kidneys to be released in urine contribute to the characteristic features of this condition.
Some studies have found variations in the SLC2A9 gene to be associated with a condition called gout, which is a form of arthritis resulting from uric acid crystals in the joints. These variants impair the GLUT9 protein's ability to release uric acid into the urine. As a result, too much uric acid is reabsorbed into the bloodstream, causing a buildup of uric acid in the body. This excess uric acid often accumulates in the body's joints in the form of crystals, leading to painful arthritis. Other studies, however, have not found an association between SLC2A9 gene variants and gout. While the role of the SLC2A9 gene in gout may be unclear, it is known that a combination of lifestyle, genetic, and environmental factors play a part in determining the risk of this complex disorder.
- glucose transporter type 9
- human glucose transporter-like protein-9
- solute carrier family 2 (facilitated glucose transporter), member 9
- solute carrier family 2, facilitated glucose transporter member 9
- urate voltage-driven efflux transporter 1