FGG

fibrinogen gamma chain

The FGG gene provides instructions for making the fibrinogen gamma (γ) 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 γ chain attaches to the fibrinogen A alpha (Aα) and fibrinogen B beta (Bβ) 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 FGG gene can lead to congenital afibrinogenemia, a condition that causes excessive bleeding due to the absence of fibrinogen protein in the blood. Most FGG gene mutations that cause this condition lead to an abnormally short blueprint for protein formation (mRNA). If any fibrinogen γ chain is produced, it is nonfunctional. Because this condition occurs when both copies of the FGG gene are altered, there is a complete absence of functional fibrinogen γ chain. Without the γ subunit, the fibrinogen protein is not assembled, which results in the absence of fibrin. As a result, 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 FGG 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 γ 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 γ 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.

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

Molecular Location: base pairs 154,604,134 to 154,612,808 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
  • FIBG_HUMAN
  • fibrinogen gamma chain isoform gamma-A precursor
  • fibrinogen gamma chain isoform gamma-B precursor
  • fibrinogen, gamma polypeptide