ADAMTS13
Chr 9ARADAM metallopeptidase with thrombospondin type 1 motif 13
Also known as: ADAM-TS13, ADAMTS-13, C9orf8, VWFCP, vWF-CP
This metalloprotease cleaves von Willebrand factor multimers in plasma to regulate platelet thrombus formation and prevent excessive clotting. Biallelic mutations cause hereditary thrombotic thrombocytopenic purpura with autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
ADAMTS13 · 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
Platelet Adhesion in the Pathobiology of Aortic Stenosis
ACTIVE NOT RECRUITINGVariations in the Hemostatic System Induced by a Standardized Walking Test
RECRUITINGEffects of Genomic Profiles on Thromboembolic Risk in Patients With Locally Advanced or Metastatic Non-small-cell Lung Cancer
RECRUITINGA Study of TAK-755 in Adults With Acute Ischemic Stroke
RECRUITINGAssociation Between the Level of EV-TF and the Occurence of Pulmonary Embolism in Patients With ARDS
RECRUITINGA Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
NOT YET RECRUITINGAspirin for Prophylaxis of TTP
NOT YET RECRUITINGTherapeutic Plasma Exchange in Septic Shock: A Pilot Study
RECRUITINGA Survey of Recombinant ADAMTS13 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
RECRUITINGEfficacy and Safety of Immunosuppression, Caplacizumab and Plasma Infusion Without Therapeutic Plasma Exchange in Immune-mediated Thrombotic Thrombocytopenic Purpura
RECRUITINGGenotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)
RECRUITINGItalian iTTP Registry
RECRUITINGExternal Resources
Links to major genomics databases and tools