Upshaw-Schulman syndrome: genes and variants

Genes linked to Upshaw-Schulman syndrome

• ADAMTS13: A disintegrin and metalloproteinase with thrombospondin motifs 13

  It cleaves ultra-large von Willebrand factor multimers in the circulation, preventing excessive platelet adhesion in small vessels. Severe inherited deficiency or inhibitory autoantibodies cause thrombotic thrombocytopenic purpura, characterized by microvascular thrombosis, thrombocytopenia, and hemolytic anemia.

  32 disease-causing and 191 uncertain variants in ADAMTS13 are linked to Upshaw-Schulman syndrome.

Where Upshaw-Schulman syndrome variants cluster

• ADAMTS13 Peptidase M12B (positions 80–286): 9 of 32 disease-causing changes, 1.9× more than its size predicts.
• ADAMTS13 CUB 1 (positions 1192–1298): 5 of 32 disease-causing changes, 2.1× more than its size predicts.
• ADAMTS13 TSP type-1 2 (positions 682–730): 3 of 32 disease-causing changes, 2.7× more than its size predicts.

Known disease-causing variants in Upshaw-Schulman syndrome

Uncertain variants in Upshaw-Schulman syndrome that look disease-causing

Which prediction tools work for Upshaw-Schulman syndrome

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 92 out of 100
• PolyPhen-2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 90 out of 100
• phyloP: 83 out of 100

Diseases related to Upshaw-Schulman syndrome

• Thrombotic thrombocytopenic purpura, also linked to ADAMTS13

Frequently asked questions

Which genes are linked to Upshaw-Schulman syndrome?

In CATVariant, Upshaw-Schulman syndrome is linked to 1 analyzed protein: ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin motifs 13).

How many genetic variants are linked to Upshaw-Schulman syndrome?

235 variants: 32 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 191 are of uncertain significance or have conflicting reports.

Which uncertain variants in Upshaw-Schulman syndrome look disease-causing?

1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ADAMTS13 D235Y. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Upshaw-Schulman syndrome?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.92, based on 24 disease-causing and 24 harmless variants).

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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