Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Protein S

The PROS1 gene encodes a protein which plays an important role in taming blood coagulation, so inactivating mutations bring about a higher risk of intravascular coagulation, increased risk of thrombosis. Protein S deficiency is inherited either autosomal dominant or recessive.

Epidemiology

The prevalence of protein C deficiency is 0,03-0,13%. This figure is much higher among patients with thromboembolic diseases (1-5%) and it might rise up to 15% among younger patient. In Patients with Cerebral infarctions occurring without apparent reason before age of 45 this figure is even 20%.

Gene Structure

The gene can be abreviated by PROS1. Its locus is on chromosom 3 (3p11.1-q11.2). Size is about 95kb and it consists of 15 exons.

Phenotype

Clinically important are thromboembolic diseases. Cerebral infarktion before age of 45 are suspect too. An aquired protein S deficiency must be excluded.

Pathology

The protein product is a vitamin K dependent cofactor for activated protein C. It is produced in liver, endothelial and cells.

Test Strategy

Patient with biochemical evidence of Protein S deficiency when a secondary reason is excluded. Family screening if a family member is a carrier.

Interpretation

The mutation is rare but the relative risk for thromboembolic diseases is is 8,2.

Genetests:

Clinic Method Carrier testing
Turnaround 5
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25
Specimen type genomic DNA

Related Diseases:

Autosomal recessive protein S deficiency
PROS1
Autosomal dominant protein S deficiency
PROS1

References:

1.

Tsuda H et al. (2002) Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency: effects on secretion and anticoagulant activity of protein S.

[^]
2.

Watkins PC et al. (1988) The gene for protein S maps near the centromere of human chromosome 3.

[^]
3.

Hoskins J et al. (1987) Cloning and characterization of human liver cDNA encoding a protein S precursor.

[^]
4.

Duchemin J et al. (1995) The Ser 460 to Pro substitution of the protein S alpha (PROS1) gene is a frequent mutation associated with free protein S (type IIa) deficiency.

[^]
5.

Douay X et al. (1998) Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke.

[^]
Update: Sept. 26, 2018