THBD Gene

The THBD gene (THBD stands for "thrombomodulin") is a protein-coding gene located at 20p11.21.

The protein encoded by the THBD gene is an endothelial-specific type I membrane receptor (thrombomodulin) that binds thrombin. Thrombomodulin forms a stoichiometric 1:1 complex with thrombin. This complex is responsible for the conversion of protein C to activated protein C (protein Ca). Activated protein C degrades clotting factors Va and VIIIa, reducing the amount of thrombin produced.

Mutations in this gene are a cause of thromboembolic diseases, also known as hereditary thrombophilia (Thrombophilia 12 due to thrombomodulin defect; OMIM: 614486)

and

hemolytic uremic syndrome, atypical 6.

The role of thrombomodulin in thrombosis is controversial. Although there are several reports of THBD mutations in patients with venous thrombosis, clear functional evidence for the pathogenicity of these mutations is lacking.

Anastasiou et al (2012) noted that thrombomodulin plays an important role in capillary beds and that THBD variations may not be associated with thrombosis in large vessels. It is likely that genetic or environmental risk factors, in addition to the THBD mutant, are involved in the pathogenesis of venous thrombosis. However, a variation in the THBD gene may be associated with an increased risk of arterial thrombosis and myocardial infarction. This association may be due to the fact that thrombomodulin can modulate inflammatory processes, complement activity, and fibrinolysis.

• Anastasiou G et al. (2012) Thrombomodulin as a regulator of the anticoagulant pathway: implication in the development of thrombosis. Blood Coagul Fibrinolysis 23: 1-10.
• Great Dane CJM et al (1998) A mutation in the thrombomodulin gene, 127G to A coding for ala25-to-thr, and the risk of myocardial infarction in men. Thromb Haemost 80: 743-748.
• Faioni EM et al (2002) Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia. Brit J Haemat 118: 595-599.
• Franchi F et al (2001) Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss. Brit J Haemat 114: 641-646.
• Kunz G et al (2000) Identification and characterization of a thrombomodulin gene mutation coding for an elongated protein with reduced expression in a kindred with myocardial infarction. Blood 95: 569-576.