The gamma component of fibrinogen polymerizes with the alpha and beta chains to form fibrin, the primary structural component of blood clots essential for hemostasis and wound repair. Mutations cause congenital afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia, presenting with bleeding disorders of variable severity. Inheritance can be either autosomal recessive or autosomal dominant depending on the specific condition and mutation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.544 OMIM phenotypes
Clinical SummaryFGG
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Gene-Disease Validity (ClinGen)
congenital fibrinogen deficiency · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.050
Z-score 3.28
OE 0.29 (0.160.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.20Z-score
OE missense 0.78 (0.690.88)
184 obs / 235.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.160.54)
00.351.4
Missense OE0.78 (0.690.88)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 7 / 24.5Missense obs/exp: 184 / 235.8Syn Z: -0.14
DN
0.6550th %ile
GOF
0.6639th %ile
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

FGG · 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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