FGA

Chr 4ARAD

fibrinogen alpha chain

Also known as: AMYLD2, Fib2

NCBI Gene: 2243 ENSG00000171560 UniProt: P02671 OMIM: 134820

This gene encodes the alpha subunit of fibrinogen, a blood coagulation factor that is cleaved by thrombin to form fibrin for blood clot formation and wound healing. Mutations cause congenital afibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia (typically autosomal recessive) as well as hereditary systemic amyloidosis (autosomal dominant). The gene shows very low constraint against loss-of-function variants, reflecting the viability of individuals with complete fibrinogen deficiency.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the alpha subunit of the coagulation factor fibrinogen, which is a component of the blood clot. Following vascular injury, the encoded preproprotein is proteolytically processed by thrombin during the conversion of fibrinogen to fibrin. Mutations in this gene lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia, afibrinogenemia and renal amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

DNmechanismAR/ADLOEUF 1.024 OMIM phenotypes

Clinical Summary— FGA

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Gene-Disease Validity (ClinGen)

congenital fibrinogen deficiency · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.46

OE 0.73 (0.53–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.67Z-score

OE missense 1.09 (1.01–1.17)

498 obs / 457.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.53–1.02)

0≤0.351.4

Missense OE?1.09 (1.01–1.17)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 25 / 34.2Missense obs/exp: 498 / 457.6Syn Z: -1.12

This gene — mechanism propensity

0.7133th %ile

GOF

0.6149th %ile

LOF

0.2777th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.