Hereditary factor IX deficiency disease: genes and variants

Genes linked to Hereditary factor IX deficiency disease

• F9: Coagulation factor IX

  Its activated form combines with factor VIIIa to efficiently activate factor X during coagulation. Pathogenic loss-of-function variants cause X-linked hemophilia B, with bleeding severity determined largely by residual factor IX activity.

  157 disease-causing and 46 uncertain variants in F9 are linked to Hereditary factor IX deficiency disease.

• 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.

  35 disease-causing and 5 uncertain variants in F8 are linked to Hereditary factor IX deficiency disease.

Where Hereditary factor IX deficiency disease variants cluster

• F8 F5/8 type C 2 (positions 2193–2345): 7 of 35 disease-causing changes, 3.1× more than its size predicts.
• F8 F5/8 type A 2 (positions 399–730): 10 of 35 disease-causing changes, 2.0× more than its size predicts.
• F9 EGF-like 1 (positions 93–129): 20 of 157 disease-causing changes, 1.6× more than its size predicts.
• F8 Plastocyanin-like 6 (positions 1887–2040): 5 of 35 disease-causing changes, 2.2× more than its size predicts.
• F8 F5/8 type C 1 (positions 2040–2188): 4 of 35 disease-causing changes, 1.8× more than its size predicts.

Known disease-causing variants in Hereditary factor IX deficiency disease

Showing 60 of 192.

Uncertain variants in Hereditary factor IX deficiency disease that look disease-causing

Which prediction tools work for Hereditary factor IX deficiency disease

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

• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 93 out of 100
• CADD: 92 out of 100
• REVEL: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 86 out of 100
• MetaLR: 79 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 Hereditary factor IX deficiency disease variants (273 disease-causing).
• Thrombophilia, X-linked, due to factor 8 defect is also caused by F8 variants; they fall mostly in different places as the Hereditary factor IX deficiency disease variants (15 disease-causing).
• Factor VIII deficiency is also caused by F8 variants; they fall mostly in different places as the Hereditary factor IX deficiency disease variants (5 disease-causing).

Diseases related to Hereditary factor IX deficiency disease

• Hereditary factor VIII deficiency disease, also linked to F8 and F9
• Thrombophilia, X-linked, due to factor 9 defect, also linked to F9
• Thrombophilia, X-linked, due to factor 8 defect, also linked to F8
• Warfarin sensitivity, X-linked, also linked to F9
• Factor VIII deficiency, also linked to F8

Frequently asked questions

Which genes are linked to Hereditary factor IX deficiency disease?

In CATVariant, Hereditary factor IX deficiency disease is linked to 2 analyzed proteins: F9 (Coagulation factor IX) and F8 (Coagulation factor VIII).

How many genetic variants are linked to Hereditary factor IX deficiency disease?

264 variants: 192 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 51 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hereditary factor IX deficiency disease look disease-causing?

7 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example F9 G412A, F9 C268W, F9 C268F, F9 C435F and F9 L369F. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Hereditary factor IX deficiency disease?

Among tools not trained on clinical labels, phyloP separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 46 disease-causing and 57 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center