The PROS1 gene provides instructions for making a protein called protein S that is important for controlling blood clotting. By itself, protein S cannot carry out the chemical reactions necessary for regulating the formation of blood clots. Instead, protein S attaches to certain enzymes and enhances their function. On the basis of this action, protein S is called a cofactor.
Protein S is made chiefly by cells in the liver. The protein circulates in the bloodstream in two forms; it is either attached (bound) to a specific protein or occurs by itself in a free form. Both forms of proteins S can act as cofactors; however, bound protein S is less effective than the free form. Protein S is a cofactor for an enzyme called activated protein C (APC). APC turns off (inactivates) the blood clotting proteins known as factor Va and factor VIIIa. Protein S also helps an enzyme known as tissue factor pathway inhibitor (TFPI) block the activity of another clotting protein, factor Xa.
Health Conditions Related to Genetic Changes
Protein S deficiency
More than 220 mutations in the PROS1 gene have been found to cause protein S deficiency. Most of these mutations change single protein building blocks (amino acids) in protein S, which disrupts its ability to act as a cofactor. Protein S deficiency can be divided into three types based on the mutation in the PROS1 gene.
Protein S deficiency type I is caused by PROS1 gene mutations that result in reduced levels of protein S. Affected individuals do not have enough protein S to control blood clotting, which causes the increased risk for abnormal blood clots in protein S deficiency.
Mutations that cause protein S deficiency type II result in the production of an altered protein S with reduced activity. Individuals with this form of the condition have normal levels of protein S, but the protein is not able to interact with other molecules involved in blood clotting. If protein S does not function properly, abnormal blood clots may form.
Protein S deficiency type III occurs when there is a low amount of free protein S, but the overall amount of protein S is normal. Because free protein S is a more effective cofactor than bound protein S, reduced levels of free protein S can disrupt the inactivation of blood clotting proteins.More About This Health Condition
Other Names for This Gene
- protein S (alpha)
- protein S, alpha
- protein S, alpha preproprotein
- protein Sa
- vitamin K-dependent plasma protein S
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Castoldi E, Hackeng TM. Regulation of coagulation by protein S. Curr Opin Hematol. 2008 Sep;15(5):529-36. doi: 10.1097/MOH.0b013e328309ec97. Citation on PubMed
- Garcia de Frutos P, Fuentes-Prior P, Hurtado B, Sala N. Molecular basis of protein S deficiency. Thromb Haemost. 2007 Sep;98(3):543-56. Citation on PubMed
- Hackeng TM, Maurissen LF, Castoldi E, Rosing J. Regulation of TFPI function by protein S. J Thromb Haemost. 2009 Jul;7 Suppl 1:165-8. doi: 10.1111/j.1538-7836.2009.03363.x. Citation on PubMed
- Pintao MC, Garcia AA, Borgel D, Alhenc-Gelas M, Spek CA, de Visser MC, Gandrille S, Reitsma PH. Gross deletions/duplications in PROS1 are relatively common in point mutation-negative hereditary protein S deficiency. Hum Genet. 2009 Sep;126(3):449-56. doi: 10.1007/s00439-009-0687-9. Epub 2009 May 23. Citation on PubMed or Free article on PubMed Central
- Ten Kate MK, Platteel M, Mulder R, Terpstra P, Nicolaes GA, Reitsma PH, van der Steege G, van der Meer J. PROS1 analysis in 87 pedigrees with hereditary protein S deficiency demonstrates striking genotype-phenotype associations. Hum Mutat. 2008 Jul;29(7):939-47. doi: 10.1002/humu.20687. Citation on PubMed
- ten Kate MK, van der Meer J. Protein S deficiency: a clinical perspective. Haemophilia. 2008 Nov;14(6):1222-8. doi: 10.1111/j.1365-2516.2008.01775.x. Epub 2008 May 7. Citation on PubMed