Protein S deficiency disease: genes and variants
Protein S deficiency disease is linked to 1 analyzed protein (PROS1). 7 DNA variants are known to cause it; 12 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Protein S deficiency disease
PROS1: Vitamin K-dependent protein S
It serves as an essential cofactor for activated protein C and also participates in TAM-receptor signaling involved in clearance of apoptotic cells. Heterozygous deficiency increases susceptibility to venous thrombosis, while severe deficiency can cause neonatal purpura fulminans.
7 disease-causing and 12 uncertain variants in PROS1 are linked to Protein S deficiency disease.
Where Protein S deficiency disease variants cluster
- PROS1 Laminin G-like 2 (positions 484–666): 3 of 7 disease-causing changes, 1.6× more than its size predicts.
Known disease-causing variants in Protein S deficiency disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PROS1 C639Y | 639 | Laminin G-like 2 | Disease-causing (★★) |
| PROS1 C666R | 666 | Laminin G-like 2 | Disease-causing (★) |
| PROS1 S324P | 324 | Laminin G-like 1 | Disease-causing (★) |
| PROS1 F72S | 72 | Gla | Disease-causing (★) |
| PROS1 R515C | 515 | Laminin G-like 2 | Disease-causing (★) |
| PROS1 P118L | 118 | EGF-like 1 | Disease-causing (★) |
| PROS1 D376N | 376 | Laminin G-like 1 | Disease-causing (★) |
Same protein, different disease
- Thrombophilia due to protein S deficiency, autosomal recessive is also caused by PROS1 variants; they fall mostly in different places as the Protein S deficiency disease variants (26 disease-causing).
Diseases related to Protein S deficiency disease
- Thrombophilia due to protein S deficiency, autosomal recessive, also linked to PROS1
Frequently asked questions
Which genes are linked to Protein S deficiency disease?
In CATVariant, Protein S deficiency disease is linked to 1 analyzed protein: PROS1 (Vitamin K-dependent protein S).
How many genetic variants are linked to Protein S deficiency disease?
19 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.
Which uncertain variants in Protein S deficiency disease look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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