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PROS1 gene
URL of this page: https://medlineplus.gov/genetics/gene/pros1/

PROS1 gene

protein S

Normal Function

The PROS1 gene provides instructions for making a protein called protein S that is important for the regulation of blood clotting. Although protein S can work on its own to inhibit certain clotting factors, it often works as a cofactor. Cofactors enhance the function of proteins that speed up chemical reactions (enzymes).

Protein S is made by cells in the liver. The protein circulates in the bloodstream in two forms; it is either attached (bound) to a specific protein, or it occurs by itself in a free form. The free form of protein S can act as 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 a protein called tissue factor pathway inhibitor (TFPI) block the activity of another clotting protein, factor Xa. This inactivation slows down the clotting process so that blood flow is not impaired. 

Health Conditions Related to Genetic Changes

Protein S deficiency

Hundreds of variants (also called mutations) in the PROS1 gene have been found to cause protein S deficiency. People with this condition have an increased risk of developing blood clots. Most of these variants change a single DNA building block (base pair) in the PROS1 gene.

Some variants in the PROS1 gene have been found to reduce the amount of available protein S. Other variants impair the function of protein S. Individuals with protein S deficiency may not have enough functional protein S to inactivate clotting proteins, which increases the risk of developing blood clots.


More About This Health Condition

Other Names for This Gene

  • PROS
  • protein S, alpha
  • PS21
  • PS22
  • PS23
  • PS24
  • PS25
  • PSA
  • THPH5
  • THPH6
  • 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

Gene and Variant Databases

References

  • Alshehri FS, Bashmeil AA, Alamar IA, Alouda SK. The natural anticoagulant protein S; hemostatic functions and deficiency. Platelets. 2024 Dec;35(1):2337907. doi: 10.1080/09537104.2024.2337907. Epub 2024 Apr 11. Citation on PubMed
  • 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
  • Gierula M, Ahnstrom J. Anticoagulant protein S-New insights on interactions and functions. J Thromb Haemost. 2020 Nov;18(11):2801-2811. doi: 10.1111/jth.15025. Epub 2020 Aug 24. Citation on PubMed
  • Gupta A, Tun AM, Gupta K, Tuma F. Protein S Deficiency. 2022 Dec 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK544344/ 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

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.