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…

Primary Disease Associations & Inheritance

Afibrinogenemia, congenitalMIM #202400

Amyloidosis, hereditary systemic 2MIM #105200

Dysfibrinogenemia, congenitalMIM #616004

Hypodysfibrinogenemia, congenitalMIM #616004

UniProtCongenital afibrinogenemia

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · congenital fibrinogen deficiency · SD · ClinGen 2020

Active trials

238

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in FGA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

1,199 rare PASS variants

Rare truncating (LoF)

1 in 660

158 rare PASS variants

Rare synonymous (reference)

1 in 120

445 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FGA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 76	1 in 640
South Asian	~43k	1 in 47	1 in 890
Remaining (unassigned)	~30k	1 in 46	1 in 820
European (Finnish)	~27k	1 in 280	≈ 1 in 13,000
Admixed American	~22k	1 in 56	1 in 720
African / African American	~21k	1 in 71	1 in 930
East Asian	~20k	1 in 52	1 in 520
Ashkenazi Jewish	~13k	1 in 240	1 in 1,400
Middle Eastern	~2,884	1 in 51	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.