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FGA gene
URL of this page: https://medlineplus.gov/genetics/gene/fga/

FGA gene

fibrinogen alpha chain

Normal Function

The FGA gene provides instructions for making a protein called the fibrinogen A alpha (Aα) chain, one piece (subunit) of the fibrinogen protein. This protein is important for blood clot formation (coagulation), which is needed to stop excessive bleeding after injury. To form fibrinogen, the Aα chain attaches to two other proteins called the fibrinogen B beta (Bβ) and fibrinogen gamma (γ) chains, each produced from different genes. Two sets of this three-protein complex combine to form functional fibrinogen.

For coagulation to occur, another protein called thrombin removes a piece from the Aα and the Bβ subunits of the functional fibrinogen protein (the pieces are called the A and B fibrinopeptides). This process converts fibrinogen to fibrin, the main protein in blood clots. Fibrin proteins attach to each other, forming a stable network that makes up the blood clot.

Health Conditions Related to Genetic Changes

Congenital afibrinogenemia

Mutations in the FGA gene can lead to congenital afibrinogenemia, a condition that causes excessive bleeding due to the absence of fibrinogen protein in the blood. Most FGA gene mutations that cause this condition lead to an abnormally short blueprint for protein formation (mRNA). If any fibrinogen Aα chain is produced, it is nonfunctional. Because this condition occurs when both copies of the FGA gene are altered, there is a complete absence of functional fibrinogen Aα chain. Without the Aα subunit, the fibrinogen protein is not assembled, which results in the absence of fibrin. Consequently, blood clots do not form in response to injury, leading to the excessive bleeding seen in people with congenital afibrinogenemia.

More About This Health Condition

Other disorders

Mutations in one or both copies of the FGA gene can cause other bleeding disorders known as hypofibrinogenemia, dysfibrinogenemia, or hypodysfibrinogenemia.

Hypofibrinogenemia is a condition characterized by decreased levels of fibrinogen in the blood. This condition is caused by mutations that reduce but do not eliminate the production of the fibrinogen Aα chain. People with hypofibrinogenemia can have bleeding problems that vary from mild to severe. Generally, the less fibrinogen in the blood, the more severe the bleeding problems are.

Dysfibrinogenemia is a condition characterized by abnormally functioning fibrinogen, although the protein is present at normal levels. This condition is usually caused by mutations that change a single protein building block (amino acid) in the fibrinogen Aα chain. These mutations alter the function of the fibrinogen protein and, depending on the functional change, can lead to excessive bleeding or abnormal blood clotting (thrombosis).

Hypodysfibrinogenemia is a condition characterized by low levels of abnormally functioning fibrinogen protein in the blood. As in dysfibrinogenemia, this condition can result in excessive bleeding or thrombosis.

Mutations in the FGA gene are also responsible for some cases of a condition called hereditary renal amyloidosis, which causes impairment of kidney (renal) function and leads to kidney failure. This condition is characterized by the accumulation of protein clumps called amyloid deposits in the kidneys. When the condition is caused by FGA gene mutations, the amyloid deposits are made up of abnormal fibrinogen Aα chain proteins, and the condition is sometimes called fibrinogen amyloidosis. The mutations involved in this condition typically change a single amino acid in the fibrinogen Aα chain and do not seem to affect fibrinogen's clotting activity.

Other Names for This Gene

  • Fib2
  • FIBA_HUMAN
  • fibrinogen alpha chain isoform alpha preproprotein
  • fibrinogen alpha chain isoform alpha-E preproprotein
  • fibrinogen, A alpha polypeptide

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

  • Tests of FGA From the National Institutes of Health

Scientific Articles on PubMed

  • PubMed From the National Institutes of Health

Catalog of Genes and Diseases from OMIM

  • AMYLOIDOSIS, HEREDITARY SYSTEMIC 2; AMYLD2
  • FIBRINOGEN, A ALPHA POLYPEPTIDE; FGA

Gene and Variant Databases

  • NCBI Gene From the National Institutes of Health
  • ClinVar From the National Institutes of Health

References

  • Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet. 1993 Mar;3(3):252-5. doi: 10.1038/ng0393-252. Citation on PubMed
  • Neerman-Arbez M, de Moerloose P, Bridel C, Honsberger A, Schonborner A, Rossier C, Peerlinck K, Claeyssens S, Di Michele D, d'Oiron R, Dreyfus M, Laubriat-Bianchin M, Dieval J, Antonarakis SE, Morris MA. Mutations in the fibrinogen aalpha gene account for the majority of cases of congenital afibrinogenemia. Blood. 2000 Jul 1;96(1):149-52. Citation on PubMed
  • Neerman-Arbez M, de Moerloose P, Honsberger A, Parlier G, Arnuti B, Biron C, Borg JY, Eber S, Meili E, Peter-Salonen K, Ripoll L, Vervel C, d'Oiron R, Staeger P, Antonarakis SE, Morris MA. Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes. Hum Genet. 2001 Mar;108(3):237-40. doi: 10.1007/s004390100469. Citation on PubMed
  • Neerman-Arbez M, Honsberger A, Antonarakis SE, Morris MA. Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia. J Clin Invest. 1999 Jan;103(2):215-8. doi: 10.1172/JCI5471. Citation on PubMed or Free article on PubMed Central
  • Neerman-Arbez M. Molecular basis of fibrinogen deficiency. Pathophysiol Haemost Thromb. 2006;35(1-2):187-98. doi: 10.1159/000093566. Citation on PubMed
  • Picken MM, Linke RP. Nephrotic syndrome due to an amyloidogenic mutation in fibrinogen A alpha chain. J Am Soc Nephrol. 2009 Aug;20(8):1681-5. doi: 10.1681/ASN.2008070813. Epub 2008 Dec 17. Citation on PubMed
  • Uemichi T, Liepnieks JJ, Benson MD. Hereditary renal amyloidosis with a novel variant fibrinogen. J Clin Invest. 1994 Feb;93(2):731-6. doi: 10.1172/JCI117027. Citation on PubMed or Free article on PubMed Central
  • Weisel JW. Fibrinogen and fibrin. Adv Protein Chem. 2005;70:247-99. doi: 10.1016/S0065-3233(05)70008-5. Citation on PubMed
DNA helix

Genomic Location

The FGA gene is found on chromosome 4.

Related Health Topics

  • Genes and Gene Therapy
  • Genetic Disorders

MEDICAL ENCYCLOPEDIA

  • Genes
  • Genetics

Understanding Genetics

  • What is DNA?
  • What is a gene?
  • What is a gene variant and how do variants occur?

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