Fibrinogen is made and secreted into the blood by liver hepatocytes. The final secreted protein is composed of two trimers each of which is composed of three polypeptide chains, Aα (also termed α) encoded by the FGA gene, Bβ (also termed β) encoded by the FGB gene, and γ encoded by the FGG gene. All three genes are located on the long or "p" arm of human chromosome 4 (at positions 4q31.3, 4q31.3, and 4q32.1, respectively). The genes are ordered FGB, FGA, and FGG and are transcribed into messenger RNA in tight synchrony. The messenger RNAs associate with the endoplasmic reticulum, translated into polypeptides, and enter the endoplasmaic reticulum where they assembled together. The assembled protein is passes to the Golgi apparatus where it is glycosylated, hydroxylated, sulfated, and phosphorylated to form the mature fibrinogen glycoprotein that is secreted into the blood.<unk>  results from inherited mutations in one of the three fibrinogen chains that results in the disruption of fibrinogen synthesis, assembly, stability, processing through the endoplasmic reticulum-Golgi apparatus pathway, and/or secretion into the blood. There are >25 fibrinogen mutations that have been associated with<unk> . The following Table lists examples of those mutations which cause<unk>  that is not associated with liver injury. The Table gives: a) each mutated protein's trivial name; b) the gene mutated (i.e. FGA, FGB, or FGG), its mutation site (i.e. numbered nucleotide in the gene beginning with the initial nucleotide base at the (start codon) of genomic DNA (as indicated by the "g." notation), and name of the nucleotides (i.e. C, T, A, G) at these sites before>after the mutation; and c) the name of the altered fibrinogen peptide (Aα, Bβ, or λ), the numbered of the amino acid changed by the mutation in the circulating peptide of the mutated fibrinogen, and the identity of the amino acids before-after the mutation using standard three letter abbreviations. In the Table, fs indicates a mutation that causes a Translational frameshift and consequently a premature stop codon (designated by "X") mutation and translation of a shortened fibrinogen chain, del is a deletion, and ins is an insertion. Trivial name Gene: mutation Polypeptide chain: mutation Trivial name Gene: mutation Polypeptide chain: mutation fibrinogen Grand Lyon FGA: g.5011_5012delCinsTTGGAATTTT (del followed by ins) Aα: Thr560PhefsX99 (fs followed by X) fibrinogen Hamilton FGB: g.7044G>T Bβ: Asp316Tyr fibrinogen Mount Eden FGB: g.8035G>A Bβ: Trp440X fibrinogen Dorfen FGG: g.75218C>T γ: Ala289Val fibrinogen Saint Germain II FGAG: g.7686A>G γ: Asn345Ser fibrinogen Muncie FGG: g.9402C>T γ: Thr371Ile As of 2016, there have been six mutations discovered to be associated with the accumulation of the mutated fibrinogen in the endoplasmic reticulum and consequential development of liver injury that may lead to liver cirrhosis, i.e. fibrinogen storage disease. Other fibrinogen mutations have also lead to their accumulation in the endoplasmic reticulum but have not been associated with liver injury perhaps because these fibrinogens are less toxic to the liver than those that cause liver injury. The following Table lists these 6 mutations. Note that all of these 6 mutations occur in the FGG gene, that all the mutations are missense mutations except for the deletion mutation of fibrinogen Anger, and that the Table reports the gene mutation site as found in cloned (as notated by "c.") rather than genomic DNA. Fibrinogen Aguadilla is the most common mutation known to cause fibrinogen storage disease. The abbreviations in this Table are defined in the previous Table. Trivial name Gene: mutation Polypeptide chain: mutation Trivial name Gene: mutation Polypeptide chain: mutation fibrinogen Brescia FGG: c.928G>C γ: Gly284Arg fibrinogen Aguadilla FGG: c.1201C>T γ: Arg375Trp (commonest mutation in fibrinogen storage disease) fibrinogen Anger FGG: c.1115_1129 (del of GAGTTTATTACCAAG) γ: G436_350 (del of intervening amino acids) fibrinogen AI DuPont FGG: c.1018A>C γ: AlaThr314Pro fibrinogen Pisa FGAG: c.1024G>A γ: Asp316Asn fibrinogen Beograd FGG: c.1174G>A γ: Gly366Ser
Congenital hypofibrinogenemia
Factor VII deficiency
Harris platelet syndrome
Acquired haemophilia
Congenital afibrinogenemia
Gray platelet syndrome
Von Willebrand disease
Dysfibrinogenemia