PROS1
Chr 3ADARprotein S
Also known as: PROS, PS21, PS22, PS23, PS24, PS25, PSA, THPH5
Protein S is a vitamin K-dependent anticoagulant plasma protein that serves as a cofactor for activated protein C in degrading coagulation factors Va and VIIIa to prevent excessive blood clotting. Mutations cause thrombophilia 5 due to protein S deficiency, which can be inherited in either autosomal dominant or autosomal recessive patterns. This gene is not highly constrained against loss-of-function variants, reflecting the fact that partial protein S deficiency is compatible with life but increases thrombotic risk.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PROS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Fertility And Sexual Function In CAH: CALLIOPE
RECRUITINGModulatory Effect of Prodigiosin or Pioglitazone on TIME and the Crosstalk to Immune-Checkpoint Protein(s)
NOT YET RECRUITINGAutophagy/Apoptosis Balance in Placental Vascular Pathologies
RECRUITINGExternal Resources
Links to major genomics databases and tools