DeCure for Thrombophilia due to protein S deficiency, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for thrombophilia due to protein S deficiency, autosomal dominant — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThrombophilia due to protein S deficiency, autosomal dominant maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for thrombophilia due to protein s deficiency, autosomal dominant is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
Protein S deficiency is an autosomal dominant disorder caused by mutations in the PROS1 gene, with almost two hundred mutations characterised as of 2007. Approximately 8% of familial thrombophilia cases are associated with protein S deficiency. In one study of 36 consecutive patients with repetitive superficial thrombophlebitis, protein S deficiency was detected in 5.5% of cases. Heterozygotes carrying one normal and one defective protein S gene are at severely increased risk of developing venous thrombosis at a young age, according to 1989 data. The same study used Southern blotting on six unrelated families and found one proband with a grossly abnormal gene pattern involving at least a deletion of the middle portion of the protein S coding sequence; family analysis showed the defect cosegregated with the deficiency.
Protein S assays are the most technically problematic of the thrombophilia assays reviewed at the College of American Pathologists Conference XXXVI. Only two papers evaluating the diagnostic use of protein S assays met the level 1 inclusion criteria for that review, and consensus recommendations emphasised the need for better standardised assays and rigorous diagnostic utility studies. The peculiar biology of protein S — it has an anticoagulant role but no enzymatic activity, and interacts with plasma components in both haemostasis and inflammation — has made it difficult to define and standardise assays for determining protein S status and its implication in thrombosis.
A 2020 case report described two patients with hereditary protein S deficiency due to the same nonsense mutation in PROS1 who had recurrent venous thromboembolism and were treated with rivaroxaban monotherapy. The authors noted it was unknown whether rivaroxaban is effective for VTE treatment in patients with thrombophilia including protein S deficiency due to lack of evidence. Historically, heparin and warfarin have been the recommended treatments. A 2024 case report discussed the dilemma of whether to screen an infant born to a mother with suspected protein S deficiency; the infant had a normal baseline coagulation profile for age and no thrombotic event in the neonatal period.
What remains missing are standardised, reliable protein S assays validated in rigorous diagnostic studies, and prospective trial data on direct oral anticoagulants in protein S deficiency patients specifically. Patient stratification by genotype and family history is not yet supported by evidence that would guide screening decisions in asymptomatic individuals.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Thrombosis and Haemostasis · 2007 · 151 citations
Molecular basis of protein S deficiency
AbstractProtein S deficiency (PSD) has been the most difficult to study among the classical inherited thrombophilic factors. This is in part due to the peculiar biology of protein S (PS), which has an anticoagulant role but no enzymatic activity, and because it interacts with plasma components that function in both haemostasis and inflammation. Clinically, it also has been difficult to define and standardise valuable assays to determine PS status and implication in thrombosis. Despite these drawbacks, at present heterozygous PS deficiency is well established as an autosomal dominant trait associated with an increased risk of thrombosis from data on familial and population studies. Almost two-hundred mutations have been characterised in PROS1, and approximately 30% of them have been characterised in vitro, clarifying the mechanisms leading to PSD. Furthermore, recent studies on the presence of large deletions in PROS1 have increased the number of PSD associated to PROS1 mutations. Finally, the discovery of new functions for PS, both in the anticoagulant system as well as in the interaction with cellular components through receptor tyrosine kinases, is broadening the importance of this molecule in the context of biomedicine.
Archives of Pathology & Laboratory Medicine · 2002 · 90 citations
A Review of the Technical, Diagnostic, and Epidemiologic Considerations for Protein S Assays
AbstractAbstract Objectives. —To review the state of the art relating to protein S deficiency as a risk factor for thrombosis and to make recommendations regarding the use of protein S measurements in the assessment of thrombotic risk in individual patients and families. Data Sources, Extraction, and Synthesis. —Selection criteria were developed for the inclusion of publications from 1985 to 2001 based on the relevant literature concerned with the systematic review of diagnostic tests. Minimal selection criteria were agreed on and the articles stratified into level 1 if they met these criteria and level 2 if they did not meet these criteria. The included articles were reviewed by the authors and abstracted onto predetermined data collection forms. These forms were then scored and recommendations based on level 1 studies. As described elsewhere, results of discussions at the College of American Pathologists Conference XXXVI on Diagnostic Issues in Thrombophilia were used to revise the manuscript into its final form. Conclusions. —Consensus was reached on 16 recommendations for the use of protein S assays in the assessment of thrombotic risk in individuals and families. Two themes run through the conclusions. First, protein S assays are the most technically problematic of the assays reviewed at this conference. Second, only 2 papers evaluating the diagnostic use of protein S assays met our level 1 inclusion criteria. These 2 problems point out the need for better standardized assays and rigorous studies of the diagnostic utility of these assays.
Partial protein S gene deletion in a family with hereditary thrombophilia
AbstractFamilial thrombophilia, the hereditary predisposition to venous thromboembolic disease, is associated with a protein S deficiency in approximately 8% of the cases. Laboratory measurements of total protein S antigen in affected families have indicated that heterozygotes, ie, individuals carrying both a normal and a defective protein S gene, are severely at risk of developing venous thrombosis at a young age. The recent isolation of protein S cDNA has enabled us to start a search for genetic defects in the protein S gene of heterozygotes. Using Southern blotting on probands of six unrelated families with hereditary protein S deficiency, one proband was found to have a grossly abnormal gene pattern. The abnormality appears to involve at least the deletion of the middle portion of the protein S coding sequence. Family analysis showed that the defect cosegregates with the protein S deficiency. These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.
Superior sagittal sinus thrombosis in a patient with protein S deficiency.
AbstractA 30-year-old man presented with sagittal sinus thrombosis. He had a history of multiple thrombotic events since adolescence, and his father had had a similar history. Laboratory studies revealed the complete absence of free protein S in his plasma. Protein S deficiency, an autosomal dominant disorder, is an identifiable cause of cerebral thrombosis. The literature and our experience with this case suggest that long-term anticoagulant therapy may prevent thrombotic episodes in patients with this disorder.
Clinical and Applied Thrombosis/Hemostasis · 2003 · 26 citations · open access
Protein S Deficiency in Repetitive Superficial Thrombophlebitis
AbstractProtein S deficiency is one of the principal congenital thrombophilias reported. The objective of this study was to assess the prevalence of protein S deficiency in patients with repetitive superficial thrombophlebitis. Thirty-six consecutive patients, 28 female and eight male, who presented with repetitive superficial thrombophlebitis (two or more cases); age range, 17 to 58 years, mean, 38.2 years; were evaluated. Coagulometry was used to determine the biologic activity of protein S. In 5.5% of the patients with repetitive superficial thrombophlebitis, protein S deficiency was detected.
A case-report of two patients with hereditary protein S deficiency treated by rivaroxaban
Abstract: Hereditary protein S deficiency is an autosomal dominant disorder associated with a high risk of venous thromboembolism (VTE) and usually results from mutations of PROS1. Historically heparin and warfarin have been applied as recommended treatment of VTE. Recent researches showed that rivaroxaban provided more consistent and predictable anticoagulation than warfarin. However, it is unknown whether rivaroxaban is effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. Here, we report two cases of recurrent VTE in two patients with hereditary protein S deficiency, owing to the same nonsense mutation in PROS1, which were successfully treated by rivaroxaban monotherapy.
Malaysian Journal of Paediatrics and Child Health · 2024 · 0 citations · open access
Contemplating Screening for Protein S Deficiency: To Screen or Not?
AbstractProtein S (PS) deficiency is a thrombophilia disorder due to the reduced activity of protein S which regulates coagulation function leading to venous thromboembolism (VTE) event. It is an autosomal dominant disorder whereby it can be heterozygous or homozygous. A positive family history of protein S deficiency is a significant risk factor for developing thromboembolism. We report a case of an infant born to a mother with suspected protein S deficiency. The dilemma is whether we should screen this infant for protein S deficiency. His baseline coagulation profile was normal according to age and had no thrombotic event throughout his neonatal period.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
