The prevalence of glycoprotein VI deficiency is unknown. At least 15 cases have been described in the scientific literature.

Glycoprotein VI deficiency can be caused by mutations in the GP6 gene, which provides instructions for making a protein called glycoprotein VI (GPVI). This protein is embedded in the outer membrane of blood cells called platelets, which are an essential component of blood clots. In response to an injury that causes bleeding, the GPVI protein begins clot formation by attaching (binding) to another protein called collagen that is found on blood vessel walls. The binding of GPVI to collagen also signals additional platelets to come together to increase the size of the clot.

GP6 gene mutations can lead to the production of no GPVI protein; an abnormally short, nonfunctional GPVI protein; or a protein that is less able to bind to collagen. Without GPVI binding to collagen, platelets cannot come together efficiently to form a clot, leading to the bleeding problems associated with glycoprotein VI deficiency.

Some cases of glycoprotein VI deficiency are not caused by GP6 gene mutations; instead these cases are acquired, which means they do not appear to be caused by inherited gene mutations. These acquired cases of glycoprotein VI deficiency are associated with autoimmune disorders such as immune thrombocytopenia purpura, Graves disease, or systemic lupus erythematosus (SLE). Autoimmune disorders occur when the immune system malfunctions and attacks the body's own cells and tissues. Some individuals with these autoimmune disorders produce immune proteins called antibodies that attack and destroy the GPVI protein. As a result, there is a shortage (deficiency) of functional GPVI protein on the surface of platelets, which leads to bleeding problems characteristic of glycoprotein VI deficiency.