Hereditary thrombocytopenia and hematologic cancer predisposition syndrome: genes and variants

Genes linked to Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

• RUNX1: Runt-related transcription factor 1

  It controls hematopoietic stem-cell emergence and later megakaryocytic and myeloid differentiation through lineage-specific transcriptional programs. Germline loss-of-function variants cause familial platelet disorder with myeloid malignancy predisposition, while somatic mutations and fusions are common in leukemia.

  39 disease-causing and 593 uncertain variants in RUNX1 are linked to Hereditary thrombocytopenia and hematologic cancer predisposition syndrome.

Where Hereditary thrombocytopenia and hematologic cancer predisposition syndrome variants cluster

• RUNX1 Runt (positions 50–178): 39 of 39 disease-causing changes, 3.5× more than its size predicts.

Known disease-causing variants in Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Which prediction tools work for Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

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

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 100 out of 100
• EVE: 100 out of 100
• MetaLR: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 88 out of 100

Same protein, different disease

• Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 is also caused by RUNX1 variants; they fall partly in the same places as the Hereditary thrombocytopenia and hematologic cancer predisposition syndrome variants (3 disease-causing).

Diseases related to Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

• Acute myeloid leukemia, also linked to RUNX1
• Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1, also linked to RUNX1

Frequently asked questions

Which genes are linked to Hereditary thrombocytopenia and hematologic cancer predisposition syndrome?

In CATVariant, Hereditary thrombocytopenia and hematologic cancer predisposition syndrome is linked to 1 analyzed protein: RUNX1 (Runt-related transcription factor 1).

How many genetic variants are linked to Hereditary thrombocytopenia and hematologic cancer predisposition syndrome?

673 variants: 39 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 593 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hereditary thrombocytopenia and hematologic cancer predisposition syndrome look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Hereditary thrombocytopenia and hematologic cancer predisposition syndrome?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 30 disease-causing and 31 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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