Thrombophilia, X-linked, due to factor 8 defect: genes and variants

Genes linked to Thrombophilia, X-linked, due to factor 8 defect

• F8: Coagulation factor VIII

  After activation, it acts as a cofactor for factor IXa and greatly accelerates factor X activation during coagulation. Loss-of-function variants cause X-linked hemophilia A, with bleeding severity determined largely by residual factor VIII activity.

  15 disease-causing and 20 uncertain variants in F8 are linked to Thrombophilia, X-linked, due to factor 8 defect.

Where Thrombophilia, X-linked, due to factor 8 defect variants cluster

• F8 Plastocyanin-like 4 (positions 583–730): 3 of 15 disease-causing changes, 3.2× more than its size predicts.
• F8 F5/8 type C 1 (positions 2040–2188): 3 of 15 disease-causing changes, 3.2× more than its size predicts.
• F8 F5/8 type A 3 (positions 1713–2040): 4 of 15 disease-causing changes, 1.9× more than its size predicts.

Known disease-causing variants in Thrombophilia, X-linked, due to factor 8 defect

Which prediction tools work for Thrombophilia, X-linked, due to factor 8 defect

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

• MetaLR: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 89 out of 100
• CADD: 89 out of 100
• PolyPhen-2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 86 out of 100
• REVEL: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Hereditary factor VIII deficiency disease is also caused by F8 variants; they fall mostly in different places as the Thrombophilia, X-linked, due to factor 8 defect variants (273 disease-causing).
• Hereditary factor IX deficiency disease is also caused by F8 variants; they fall mostly in different places as the Thrombophilia, X-linked, due to factor 8 defect variants (35 disease-causing).
• Factor VIII deficiency is also caused by F8 variants; they fall mostly in different places as the Thrombophilia, X-linked, due to factor 8 defect variants (5 disease-causing).

Diseases related to Thrombophilia, X-linked, due to factor 8 defect

• Hereditary factor VIII deficiency disease, also linked to F8
• Hereditary factor IX deficiency disease, also linked to F8
• Factor VIII deficiency, also linked to F8

Frequently asked questions

Which genes are linked to Thrombophilia, X-linked, due to factor 8 defect?

In CATVariant, Thrombophilia, X-linked, due to factor 8 defect is linked to 1 analyzed protein: F8 (Coagulation factor VIII).

How many genetic variants are linked to Thrombophilia, X-linked, due to factor 8 defect?

35 variants: 15 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 20 are of uncertain significance or have conflicting reports.

Which uncertain variants in Thrombophilia, X-linked, due to factor 8 defect 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 Thrombophilia, X-linked, due to factor 8 defect?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.89, based on 12 disease-causing and 37 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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