FGA

Chr 4ARAD

fibrinogen alpha chain

Also known as: AMYLD2, Fib2

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAR/ADLOEUF 1.024 OMIM phenotypes
Clinical SummaryFGA
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Gene-Disease Validity (ClinGen)
congenital fibrinogen deficiency · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.46
OE 0.73 (0.531.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.67Z-score
OE missense 1.09 (1.011.17)
498 obs / 457.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.73 (0.531.02)
00.351.4
Missense OE1.09 (1.011.17)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 25 / 34.2Missense obs/exp: 498 / 457.6Syn Z: -1.12
DN
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FGA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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