SLC2A10

At least 23 SLC2A10 gene mutations have been identified in people with arterial tortuosity syndrome, a connective tissue disorder characterized by abnormal curving and twisting (tortuosity) of the blood vessels that carry blood from the heart to the rest of the body (arteries) and other health problems.

The mutations that cause arterial tortuosity syndrome reduce or eliminate GLUT10 function. By mechanisms that are not well understood, a lack (deficiency) of functional GLUT10 protein leads to overactivity (upregulation) of TGF-β signaling. Excessive growth signaling results in elongation of the arteries. Since the end points of the arteries are fixed, the extra length twists and curves, leading to tortuosity. Overactive TGF-β signaling also interferes with normal formation of the connective tissues in other parts of the body, leading to the joint and skin abnormalities and other features of arterial tortuosity syndrome.

Changes in mitochondrial function related to GLUT10 deficiency may also affect cardiovascular system development, but the relationship between mitochondrial function and the specific signs and symptoms of arterial tortuosity syndrome is unclear.

Several normal variations (polymorphisms) of the SLC2A10 gene have been associated with an increased risk of peripheral artery disease in people with type 2 diabetes, a disorder in which resistance to the hormone insulin leads to excess glucose levels in the blood (hyperglycemia). Peripheral artery disease is a condition in which an accumulation of fatty deposits and scar-like tissue in the lining of the arteries (atherosclerosis) reduces blood flow to the legs, causing pain when walking. Problems with blood vessels, including peripheral artery disease, are common in type 2 diabetes, and are believed to be related to the effect of hyperglycemia on TGF-β signaling. Alterations in the GLUT10 protein caused by SLC2A10 gene variations may also affect TGF-β signaling and increase the risk of blood vessel problems in diabetes.