fibrinogen alpha chain

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.

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.

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.

Cytogenetic Location: 4q28, which is the long (q) arm of chromosome 4 at position 28

Molecular Location: base pairs 154,583,126 to 154,590,766 on chromosome 4 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 4q28, which is the long (q) arm of chromosome 4 at position 28
  • Fib2
  • fibrinogen alpha chain isoform alpha-E preproprotein
  • fibrinogen alpha chain isoform alpha preproprotein
  • fibrinogen, A alpha polypeptide