Academic Journal
An interactive human PROS1 variants database provides novel insights into the genetics and phenotypes of inherited protein S deficiency.
| Τίτλος: | An interactive human PROS1 variants database provides novel insights into the genetics and phenotypes of inherited protein S deficiency. |
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| Συγγραφείς: | Hou Z; Department of hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China; Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China; International Center for Aging and Cancer, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, People's Republic of China., Liu F; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Dong S; Department of hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Guo Y; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Yu X; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Ai LJ; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Zhang M; Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Kang J; Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Jiang B; Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Dong Y; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Zhao M; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China; Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Pan J; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Zhang S; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China., Zhao W; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China. Electronic address: zhaowr@hrbmu.edu.cn., Wang W; Department of hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China. Electronic address: ww0543@163.com., Hao D; Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China. Electronic address: dapenghao@hrbmu.edu.cn., Shen G; Department of hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China; Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China. Electronic address: shenba433@163.com. |
| Πηγή: | Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2026 Jul; Vol. 24 (7), pp. 2579-2592. Date of Electronic Publication: 2026 Apr 10. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7836 (Electronic) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : [New York] : Elsevier Original Publication: Oxford : Blackwell Pub. |
| Ιατρικοί όροι (MeSH): | Protein S Deficiency*/genetics , Protein S Deficiency*/blood , Protein S Deficiency*/diagnosis , Protein S Deficiency*/epidemiology , Blood Proteins*/genetics , Databases, Genetic* , Genetic Variation*, Thrombosis/genetics ; Thrombosis/blood ; Thrombosis/epidemiology ; Protein S/metabolism ; Humans ; Phenotype ; Genetic Predisposition to Disease ; Genetic Association Studies ; Risk Factors ; Female ; Age of Onset ; Risk Assessment ; Male ; Mutation ; Adult |
| Περίληψη: | Background: The lack of an interactive PROS1 variant database has impeded efficient research on inherited protein S deficiency (PSD). Objectives: We aimed to develop an interactive PROS1 variant database for studying PSD epidemiology, genotype-phenotype correlations, and variant pathogenicity, thereby improving thrombotic risk prediction and clinical decision-making. Methods: We constructed an interactive database by systematically collating inherited PSD data from PubMed. The American College of Medical Genetics and Genomics classification was performed to explore variant pathogenicity. Statistical analyses were performed to investigate the epidemiology, clinical characteristics, genotype-phenotype correlations, and thrombosis risk assessment in PSD. Results: The database comprises 520 unique PROS1 variants identified from 2177 individuals with PSD, including 88 biallelic variant (BV) cases and 2089 monoallelic variant (MV) cases. More than 91% of variants are pathogenic or likely pathogenic based on the American College of Medical Genetics and Genomics classification. Certain variants demonstrate ethnic or geographic specificity. While the spectra of clinical presentations are similar between BV and MV individuals, BV carriers have a significantly earlier onset age. In BV individuals, total protein S (PS) and free PS levels, but not PS activity, show a correlation with the first-onset age. Notably, total PS in type III MV individuals is well correlated with their first-onset age, and these cases show a significantly lower frequency of symptoms and recurrent/multiple episodes, as well as later first-onset age. Furthermore, coexistence of other thrombophilia factors increases thrombosis risk of MV individuals. Conclusion: This database provided a valuable resource for retrieving pathogenic PROS1 variants and associated clinical data, enhancing our understanding of thrombotic risk in PSD and facilitating precision medicine for PSD. (Copyright © 2026 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interests There are no competing interests to disclose. |
| Contributed Indexing: | Keywords: genotype-phenotype; protein S deficiency; thrombophilia factors; thrombosis; variant database |
| Substance Nomenclature: | 0 (PROS1 protein, human) 0 (Protein S) 0 (Blood Proteins) |
| Entry Date(s): | Date Created: 20260412 Date Completed: 20260618 Latest Revision: 20260618 |
| Update Code: | 20260619 |
| DOI: | 10.1016/j.jtha.2026.04.004 |
| PMID: | 41967715 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1538-7836 |
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| DOI: | 10.1016/j.jtha.2026.04.004 |