Familial dysfibrinogenemia: genes and variants

Genes linked to Familial dysfibrinogenemia

• FGG: Fibrinogen gamma chain

  It contributes the gamma chains of fibrinogen and provides binding sites important for fibrin polymerization, platelet interactions, and clot stabilization. Pathogenic variants can cause quantitative or qualitative fibrinogen disorders and, in some alleles, hereditary renal amyloidosis.

  9 disease-causing and 7 uncertain variants in FGG are linked to Familial dysfibrinogenemia.

• FGA: Fibrinogen alpha chain

  It contributes the alpha chains of fibrinogen, which thrombin converts into fibrin to form the structural mesh of blood clots. Pathogenic variants can cause afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, thrombosis, or certain hereditary amyloidoses.

  3 disease-causing and 52 uncertain variants in FGA are linked to Familial dysfibrinogenemia.

• FGB: Fibrinogen beta chain

  It contributes the beta chains required for assembly and secretion of functional fibrinogen and subsequent fibrin-clot formation. Pathogenic variants can reduce fibrinogen quantity or alter clot properties, producing bleeding, thrombosis, or both.

  2 disease-causing and 8 uncertain variants in FGB are linked to Familial dysfibrinogenemia.

Where Familial dysfibrinogenemia variants cluster

• FGG Fibrinogen C-terminal (positions 170–416): 9 of 9 disease-causing changes, 1.8× more than its size predicts.

Known disease-causing variants in Familial dysfibrinogenemia

Which prediction tools work for Familial dysfibrinogenemia

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

• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 96 out of 100
• PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 95 out of 100
• phyloP: 95 out of 100

Same protein, different disease

• Afibrinogenemia is also caused by FGB variants; they fall mostly in different places as the Familial dysfibrinogenemia variants (5 disease-causing).

Diseases related to Familial dysfibrinogenemia

• Hypertrophic cardiomyopathy, also linked to FGA, FGB and FGG
• Noonan syndrome, also linked to FGA, FGB and FGG
• Costello syndrome, also linked to FGA, FGB and FGG
• Afibrinogenemia, also linked to FGA, FGB and FGG
• Hereditary spastic paraplegia, also linked to FGG
• Deep venous thrombosis, also linked to FGA
• Familial visceral amyloidosis, Ostertag type, also linked to FGA

Frequently asked questions

Which genes are linked to Familial dysfibrinogenemia?

In CATVariant, Familial dysfibrinogenemia is linked to 3 analyzed proteins: FGG (Fibrinogen gamma chain), FGA (Fibrinogen alpha chain) and FGB (Fibrinogen beta chain).

How many genetic variants are linked to Familial dysfibrinogenemia?

104 variants: 14 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 67 are of uncertain significance or have conflicting reports.

Which uncertain variants in Familial dysfibrinogenemia 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 Familial dysfibrinogenemia?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 12 disease-causing and 17 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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