Affinage

FGA

Fibrinogen alpha chain · UniProt P02671

Round 2 corrected
Length
866 aa
Mass
95.0 kDa
Annotated
2026-04-28
111 papers in source corpus 27 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGA encodes the fibrinogen Aα chain, an essential subunit of the (AαBβγ)₂ hexameric fibrinogen complex that is assembled in hepatocytes and secreted into plasma, where thrombin cleavage of fibrinopeptide A exposes the 'knob A' (Gly-Pro-Arg) polymerization site to initiate fibrin clot formation (PMID:7356959, PMID:9333233, PMID:19296670). Loss-of-function mutations in FGA—including large deletions, splice-site mutations, and start-codon disruption—cause congenital afibrinogenemia, while missense mutations in the αC-region (e.g., E540V, R554L) confer amyloidogenicity and underlie hereditary renal amyloidosis, the most commonly misdiagnosed form of systemic amyloidosis (PMID:9916133, PMID:12050338, PMID:27126074). FGA transcription in hepatocytes is driven by the PFE2 liver enhancer and regulated by HDAC2-dependent H3K9 acetylation at its promoter; FGA mRNA is produced in stoichiometric excess over FGB and FGG, with the γ chain being rate-limiting for fibrinogen secretion (PMID:22836734, PMID:23414568, PMID:40605115). Beyond hemostasis, fibrinogen bridges leukocytes to endothelium via ICAM-1, and ectopic FGA expression suppresses cancer cell invasion by repressing ITGA5/FAK/ERK and PI3K/AKT signaling (PMID:8100742, PMID:35257941, PMID:39227068).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1980 High

    Defining the structural basis of fibrin polymerization initiation: synthetic Gly-Pro-Arg peptides established that the newly exposed Aα N-terminus constitutes the 'knob A' donor site and defined the minimal sequence requirements for knob–hole interaction.

    Evidence Synthetic peptide binding and fibrin polymerization inhibition assays using purified fibrinogen

    PMID:7356959

    Open questions at the time
    • Acceptor (hole) site structure not yet resolved
    • In vivo relevance of peptide inhibition not tested
    • Contribution of knob B not addressed
  2. 1993 High

    Establishing fibrinogen as a vascular adhesion bridge: fibrinogen was shown to mediate leukocyte–endothelial adhesion by engaging ICAM-1 as a novel fibrinogen receptor, expanding the Aα chain's role beyond coagulation to inflammation.

    Evidence Affinity chromatography, ICAM-1 transfectant binding assays, and adhesion blocking antibody experiments

    PMID:8100742

    Open questions at the time
    • Binding site on Aα chain for ICAM-1 not mapped
    • Relative contribution of Aα vs. Bβ/γ chains to ICAM-1 interaction unknown
    • In vivo leukocyte trafficking consequences not tested
  3. 1997 High

    Resolving the three-dimensional architecture of fibrinogen's functional domains: the crystal structure of fragment D and the double-D:Gly-Pro-Arg-Pro complex revealed the coiled-coil scaffold, globular D-domain topology, and the structural basis of knob–hole polymerization.

    Evidence X-ray crystallography at 2.9 Å resolution with polymerization-site peptide ligand

    PMID:9333233

    Open questions at the time
    • Full-length hexamer structure not yet available
    • αC-region structure unresolved
    • Dynamic conformational changes during polymerization not captured
  4. 1999 High

    Proving FGA is essential for fibrinogen biogenesis in humans: an 11 kb homozygous FGA deletion was identified as the cause of congenital afibrinogenemia, and the deletion mechanism was traced to illegitimate recombination at a 7 bp direct repeat.

    Evidence Southern blotting, PCR, haplotype analysis of pedigrees; deletion junction sequencing across three independent chromosomes

    PMID:10602365 PMID:9916133

    Open questions at the time
    • Contribution of individual FGA domains to intracellular assembly not dissected
    • Non-hepatic consequences of complete FGA loss not explored
  5. 2001 High

    Elucidating how FGA splice-site mutations produce null alleles: the most common afibrinogenemia mutation (IVS4+1G>T) activates cryptic splice donors causing frameshifts, and intron removal order determines whether a splice mutation causes exon skipping or cryptic-site usage.

    Evidence Minigene transfection in COS-7 cells with RT-PCR characterization of multiple mutations (IVS4, IVS3, IVS1)

    PMID:11238133 PMID:12406899

    Open questions at the time
    • Nonsense-mediated decay contribution not quantified at this stage
    • Patient-to-patient variation in aberrant transcript ratios not assessed
  6. 2002 High

    Identifying FGA mutations as the leading cause of hereditary renal amyloidosis: systematic screening of 350 patients revealed that Aα C-terminal variants are the most common genetic cause of systemic amyloidosis misdiagnosed as AL type.

    Evidence Genetic screening with histological and laboratory confirmation across a large patient cohort

    PMID:12050338

    Open questions at the time
    • Mechanism by which αC variants convert to amyloid fibrils not established at molecular level
    • Tissue tropism for kidney not explained
  7. 2009 High

    Completing the hexameric fibrinogen structure: the full-length (AαBβγ)₂ crystal structure at 3.3 Å confirmed the coiled-coil arrangement, β-chain carbohydrate positions, and an antiparallel β-chain interface, though the αC domains remained unresolved.

    Evidence X-ray crystallography of intact human fibrinogen

    PMID:19296670

    Open questions at the time
    • αC-region remains structurally unresolved
    • No structure of fibrinogen in complex with thrombin or cellular receptors
  8. 2012 Medium

    Defining cis-regulatory and mRNA-level control of FGA expression: the PFE2 enhancer was validated as a hepatocyte-specific element driving FGA transcription, and siRNA experiments demonstrated that FGA mRNA is in stoichiometric excess, with FGG being rate-limiting for fibrinogen secretion.

    Evidence Luciferase reporter assays in hepatoma cells; transgenic zebrafish GFP reporter; siRNA knockdown of each fibrinogen chain in HepG2 with secreted fibrinogen ELISA

    PMID:22836734 PMID:23414568

    Open questions at the time
    • Transcription factor(s) binding PFE2 not identified
    • Post-transcriptional regulation of chain stoichiometry not addressed
    • In vivo validation of stoichiometric excess in human liver lacking
  9. 2014 High

    Demonstrating FGA sufficiency for fibrinogen rescue: lentiviral delivery of FGA cDNA into afibrinogenemia patient hepatocytes restored functional hexamer secretion, and zebrafish fga knockouts recapitulated human afibrinogenemia with hemorrhage and lethality.

    Evidence Lentiviral transduction of patient hepatocytes with fibrinogen functional assays; zinc finger nuclease knockout zebrafish with hemorrhage scoring and survival analysis

    PMID:24553182 PMID:25163824

    Open questions at the time
    • In vivo gene therapy efficacy and durability not assessed
    • Long-term hemostatic function in zebrafish not followed
  10. 2016 Medium

    Establishing molecular mechanisms of amyloidogenic αC-region variants: in vitro aggregation of recombinant FGA(496-581) showed that E540V forms amyloid-like fibrils and R554L forms β-sheet-rich aggregates at physiological pH, while wild-type remains monomeric, directly linking point mutations to pathological misfolding.

    Evidence Recombinant fragment aggregation assays with AFM imaging and circular dichroism

    PMID:27126074

    Open questions at the time
    • Nucleation mechanism and kinetics not determined
    • Kidney-specific amyloid deposition not explained
    • No structural model of fibril at atomic resolution
  11. 2022 High

    Uncoupling the αC-region from essential hemostatic function: mice with a premature stop at Aα residue 271 had ~10% plasma fibrinogen (via NMD) yet showed normal hemostasis, preserved platelet fibrinogen with compensatory fibronectin, and full protection from venous thrombosis—demonstrating that the αC-region is dispensable for hemostasis but critical for maintaining plasma fibrinogen levels.

    Evidence Targeted knock-in mouse; tail bleeding, laser injury, IVC stasis thrombosis, bacterial peritonitis models; platelet proteomics

    PMID:34905618

    Open questions at the time
    • Mechanism of platelet fibrinogen preservation not fully explained
    • αC-region contribution to fibrin clot mechanical properties in vivo not tested
    • Wound healing and tissue repair outcomes not evaluated
  12. 2022 Medium

    Revealing non-hemostatic signaling roles of FGA: in cancer cells, FGA represses ITGA5 transcription (via promoter binding) to suppress FAK/ERK signaling, migration, and invasion; in hepatocellular carcinoma, FGA loss activates PI3K/AKT; and in endometrial stromal cells, FGA promotes angiogenesis through a VEGFA-VEGFR2-FAK axis.

    Evidence FGA overexpression/knockout in gastric and hepatocellular carcinoma cells with ChIP, luciferase, xenograft models; siRNA in endometrial stromal cells with conditioned medium HUVEC assays

    PMID:35257941 PMID:35498401 PMID:39227068

    Open questions at the time
    • Whether circulating fibrinogen or locally produced Aα chain mediates these effects is unclear
    • Direct DNA-binding domain of FGA not identified
    • Relevance to in vivo tumor biology in patients not established
  13. 2025 Medium

    Linking epigenetic regulation to FGA's role in reproductive biology: HDAC2 was shown to control chromatin accessibility and H3K9ac at the FGA promoter in granulosa cells, where FGA promotes proliferation and suppresses apoptosis to support pubertal initiation.

    Evidence HDAC2 siRNA, ATAC-seq, ChIP for H3K9ac, FGA knockdown/overexpression in granulosa cells, in vivo mouse puberty model

    PMID:40605115

    Open questions at the time
    • Whether FGA functions intracellularly or as a secreted factor in granulosa cells is unknown
    • Relationship between granulosa FGA and circulating fibrinogen not addressed
    • Upstream signals regulating HDAC2 at FGA promoter not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic structure of the αC-region and the structural basis of its amyloidogenic conversion; the mechanism by which FGA represses gene transcription (e.g., ITGA5) in non-hepatic cells; and whether therapeutic reduction of αC-region length can prevent thrombosis without hemostatic compromise in humans.
  • No high-resolution structure of the αC domain
  • No identified DNA-binding or transcription-regulatory domain in FGA
  • Clinical translation of αC-truncation antithrombotic strategy untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0048018 receptor ligand activity 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005576 extracellular region 6 GO:0031012 extracellular matrix 1
Pathway
R-HSA-109582 Hemostasis 7 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
FAKFGBFGGHDAC2ICAM1ITGA5VEGFR2
Complex memberships
Fibrinogen (AαBβγ)₂ hexamer

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Homozygous deletion of approximately 11 kb of the fibrinogen alpha-chain gene (FGA) causes complete absence of fibrinogen (congenital afibrinogenemia), establishing that FGA is required for fibrinogen synthesis and secretion in humans, analogous to findings in mice. Southern blotting, PCR, haplotype analysis of affected pedigree members The Journal of clinical investigation High 9916133
1999 The recurrent 11 kb FGA deletion arises from non-homologous (illegitimate) recombination mediated by a 7 bp direct repeat (AACTTTT) located in FGA intron 1 and the FGA-FGB intergenic sequence, together with flanking inverted repeats that can form secondary structures. Nucleotide sequence analysis of deletion junctions, comparison with normal sequences, flanking polymorphic marker haplotyping European journal of human genetics High 10602365
2001 The most common congenital afibrinogenemia mutation, FGA IVS4+1G>T, causes aberrant mRNA splicing by activating multiple cryptic donor splice sites in exon 4 and intron 4; the predominant cryptic site (4 bp downstream) is used in 85% of transcripts, causing a frameshift and premature Aα-chain truncation (null allele). Transfection of normal and mutant minigene constructs into COS-7 cells, RT-PCR analysis of aberrant mRNA products Blood High 11238133
2002 The outcome of FGA donor splice-site mutations reflects the order of intron removal: intron 3 is spliced first, followed by intron 2, intron 4, and intron 1. Mutations in rapidly spliced introns (e.g., IVS3) predominantly cause exon skipping, while mutations in later-spliced introns (e.g., IVS4) lead to cryptic splice-site utilization or intron inclusion. Minigene transfection in COS-7 cells, RT-PCR analysis of splicing outcomes for IVS3delGTAA and IVS1+3A>G mutations Blood High 12406899
1997 Crystal structure of fibrinogen fragment D (from human fibrinogen) determined at 2.9 Å resolution, revealing a three-chained structure with a coiled-coil region and two homologous globular entities oriented ~130° to each other; the double-D fragment from fibrin, solved with a Gly-Pro-Arg-Pro-amide peptide ligand, defined the donor polymerization site. X-ray crystallography at 2.9 Å; molecular replacement for double-D Nature High 9333233
2009 Crystal structure of human fibrinogen determined at ~3.3 Å resolution, revealing the full hexameric (AαBβγ)₂ arrangement, coiled-coil regions with variable twist, an antiparallel β-chain interface, and prominent carbohydrate groups on β chains; αC domains were not resolvable. X-ray crystallography Biochemistry High 19296670
1980 Synthetic Gly-Pro-Arg peptides bind to fibrinogen and inhibit fibrin polymerization, defining the fibrin polymerization ('knob A') site on the Aα chain and establishing the structural requirements for donor-acceptor interactions in fibrin assembly. Synthetic peptide binding assays, fibrin polymerization inhibition, species-difference analysis Biochemistry High 7356959
1993 Fibrinogen mediates leukocyte adhesion to vascular endothelium through a mechanism requiring ICAM-1 on endothelial cells; fibrinogen bridges leukocytes and endothelium by binding complementary receptors on both cell types, with ICAM-1 identified as a novel hematopoietic fibrinogen receptor by affinity chromatography and direct binding to recombinant protein. Affinity chromatography purification, genetically engineered ICAM-1 transfectants, direct binding assays, adhesion assays with blocking antibodies Cell High 8100742
2002 Fibrinogen alpha-chain (FGA) is a secreted glycoprotein phosphorylated at S-x-E motifs in the secretory pathway; Fam20C (Golgi casein kinase) phosphorylates FGA as part of the broader extracellular phosphoproteome. Mass spectrometry identification of phosphorylation sites; CRISPR/Cas9 Fam20C knockout followed by secreted phosphoproteome analysis Science / Cell Medium 22582013 26091039
2002 Misdiagnosis study established that fibrinogen Aα-chain (FGA) mutations are the most common cause of hereditary systemic amyloidosis misdiagnosed as AL amyloidosis, confirming that mutant FGA protein deposits as amyloid primarily in kidneys. Genetic screening for amyloidogenic mutations in 350 patients; histological and laboratory confirmation of hereditary amyloidosis The New England journal of medicine High 12050338
2016 Two familial FGA mutations associated with renal amyloidosis (E540V and R554L in the C-terminal αC-region fragment FGA(496-581)) enhance amyloidogenicity: E540V causes amyloid-like fibril formation and R554L causes globular β-sheet-rich aggregates at physiological pH, whereas wild-type FGA(496-581) remains monomeric. In vitro aggregation assays of recombinant FGA(496-581) fragments; atomic force microscopy (AFM); circular dichroism for β-sheet content Biochimie Medium 27126074
2010 A novel nonsense mutation in FGA exon 5 (c.718C>T, p.Q240X) causes afibrinogenemia; expression of the mutant Aα-chain cDNA with wild-type Bβ and γ chains in COS-7 cells showed the truncated chain is produced but less efficiently secreted than wild-type, establishing that the Aα Q240X truncation impairs fibrinogen secretion rather than synthesis. COS-7 cell co-transfection of mutant and wild-type fibrinogen chain cDNAs; immunodetection in cell media Blood coagulation & fibrinolysis Medium 20051841
2012 A novel regulatory element (PFE2) located between FGA and FGG genes functions as a potent hepatocyte enhancer in both orientations; PFE2 enhances FGA promoter-driven gene expression in hepatoma cells and drives EGFP expression in transgenic zebrafish larval livers, identifying a cis-regulatory element controlling FGA transcription. Luciferase reporter assays in hepatoma cells; transgenic zebrafish GFP reporter assay; ChIP-seq data integration Thrombosis and haemostasis Medium 22836734
2013 siRNA-mediated knockdown of FGA mRNA by ~50% in HepG2 cells reduces secreted fibrinogen to only 78% of control, whereas equivalent knockdown of FGB or FGG reduces fibrinogen to 49% or 57%, demonstrating that FGA mRNA is present in excess relative to FGB and FGG, and that FGG mRNA is the rate-limiting component for fibrinogen expression in normal liver. siRNA knockdown of individual fibrinogen chains in HepG2 cells; quantitative RT-PCR for mRNA levels; ELISA for secreted fibrinogen Thrombosis research Medium 23414568
2014 Zinc finger nuclease-mediated frameshift mutations in zebrafish fga produce homozygous fish with undetectable plasma fibrinogen, hemorrhaging, and reduced survival, validating fga as the causative locus for afibrinogenemia and establishing the first transmissible zebrafish model of this human bleeding disorder. Zinc finger nuclease gene targeting; anti-fibrinogen antibody detection in plasma; hemorrhage phenotype scoring; survival analysis Blood High 24553182
2014 Lentiviral transduction of the human FGA cDNA into hepatocytes from an afibrinogenemia patient (homozygous FGA deletion) restores Aα-chain expression and secretion of fully functional fibrinogen hexamer in vitro, demonstrating that gene delivery of FGA alone is sufficient for functional fibrinogen assembly and secretion. Lentiviral vector transduction of patient-derived hepatocytes; functional fibrinogen assays in conditioned media Journal of thrombosis and haemostasis Medium 25163824
2016 The FGA variant c.169_180+2 del (fibrinogen Shanghai) causes exon 2 skipping, producing a shortened Aα chain with 42 N-terminal amino acid truncation; patient fibrinogen shows impaired fibrinopeptide A release by thrombin, prolonged polymerization lag time, slower maximum slope, reduced final turbidity, and thicker fibres with looser clot network by scanning electron microscopy, without affecting fibrinogen synthesis or secretion. FGA minigene transfection splicing assay; turbidimetric fibrin polymerization and lysis assays; reversed-phase HPLC for fibrinopeptide release; scanning electron microscopy of fibrin clots Journal of clinical pathology High 27555433
2017 The FGA mutation p.Arg104Cys (g.3057C>T) causes hypodysfibrinogenemia; mass spectrometry (TOF-MS) showed the variant Aα chain represents only ~25% of total circulating Aα chain, indicating impaired secretion of the mutant chain. Plasmin degradation and fibrinogen-albumin complex formation were normal, while clot structure was nearly normal by confocal microscopy. Reverse phase-electrospray TOF-MS for chain quantification; turbidimetric polymerization; immunoblotting for albumin complexes; confocal microscopy of clot structure; SDS-PAGE of plasmin degradation products BMC hematology Medium 29299315
2022 Mice carrying the Fga270 premature termination codon (at residue 271, within the αC-region) are hypofibrinogenemic (~10% plasma fibrinogen) due to nonsense-mediated decay of mutant Fga mRNA (90% reduction in hepatic mRNA); despite low plasma fibrinogen, these mice have preserved hemostasis in tail bleeding and laser-injury models, normal initial platelet aggregation, and are fully protected from venous thrombosis (IVC stasis model). Platelet fibrinogen is ~30% of wild-type with compensatory fibronectin increase, revealing that αC-region truncation selectively reduces plasma but partially preserves platelet fibrinogen. Targeted mouse knock-in; plasma fibrinogen ELISA; hepatic mRNA quantification; tail bleeding assay; laser-induced saphenous vein injury; IVC stasis thrombosis model; platelet aggregometry; platelet fibrinogen and fibronectin quantification; S. aureus peritonitis survival model Blood High 34905618
2022 FGA (fibrinogen alpha chain) knockdown in endometrial stromal cells reduces VEGFA, PDGF, FGF-B, MMP-2, and MMP-9 expression, and the conditioned medium from FGA-knockdown cells inhibits HUVEC tube formation, migration, VE-cadherin expression, microfilament formation, and suppresses VEGFR2 and FAK signaling, establishing that FGA promotes angiogenesis via a VEGFA-VEGFR2-FAK signaling axis. FGA siRNA knockdown in endometrial stromal cells; conditioned medium transfer to HUVECs; tube formation assay; wound/transwell migration assays; matrigel plug assay in vivo; Western blotting for VEGFR2/FAK phosphorylation; immunofluorescence for F-actin/VE-cadherin Frontiers in endocrinology Medium 35498401
2022 FGA overexpression in gastric cancer cells suppresses ITGA5 (Integrin-α5) transcription (confirmed by luciferase and ChIP assays), inhibits FAK/ERK pathway activity, suppresses migration, invasion, EMT, and induces autophagy; FGA knockout activates FAK/ERK and promotes tumor growth in nude mouse xenografts. FGA overexpression/knockout cell models; transwell and wound healing assays; luciferase reporter and ChIP assays for ITGA5 transcription; Western blotting for FAK/ERK; RFP-GFP-LC3 autophagy assay; in vivo xenograft Tissue & cell Medium 35257941
2024 FGA overexpression in hepatocellular carcinoma cells increases E-cadherin and decreases N-cadherin and Slug (EMT markers), inhibits cell migration and invasion; FGA knockout activates the PI3K/AKT pathway, and FGA overexpression restricts tumor spread in a mouse metastasis model. FGA overexpression and knockout cell models; Transwell migration/invasion assays; wound healing assay; Western blotting for EMT markers and PI3K/AKT; in vivo mouse metastasis model Aging Medium 39227068
2023 Computational modeling and in vitro aggregation experiments show that vitamin C and vitamin D3 interact with amyloidogenic sites of E524K and E526K FGA C-terminal mutants, reducing amyloid fibril formation; Congo red assays, aggregation index measurements, and AFM imaging confirm smaller aggregates in the presence of vitamin D3. Molecular docking; MD simulation-derived binding free energy; Congo red absorbance; aggregation index; AFM imaging of aggregates The Journal of steroid biochemistry and molecular biology Low 36907427
2025 FGA expression in granulosa cells is regulated by histone acetylation: HDAC2 knockdown reduces chromatin accessibility and H3K9ac enrichment at the FGA promoter region (-1350/-1454 bp), suppressing FGA transcription. FGA promotes granulosa cell proliferation and cell cycle progression (upregulating PCNA and CCNE1) and inhibits apoptosis (suppressing Caspase3 and Caspase9) both in vitro and in vivo, advancing pubertal initiation in mice. HDAC1/2/3 siRNA knockdown; ATAC-seq for chromatin accessibility; ChIP for H3K9ac at FGA promoter; FGA knockdown/overexpression in granulosa cells; flow cytometry for cell cycle/apoptosis; Western blotting for PCNA, CCNE1, Caspase3/9; in vivo mouse model for corpora lutea and estradiol Biological research Medium 40605115
2012 A minigene corresponding to the FGAΔ1238 deletion generates two aberrant mRNAs with frameshifts causing premature termination; the FGA c.54+3A>C substitution activates a cryptic 5' splice site in exon 1, producing one transcript with a frameshift and another deleting six amino acids from the signal peptide, both predicted to impair Aα-chain assembly/secretion. Minigene cloning and transfection into CHO cells; RT-PCR and sequencing of aberrant mRNAs International journal of hematology Medium 22639050
2012 A mutation of the FGA translation initiation codon (c.1A>T, M1L) causes congenital afibrinogenemia, establishing that the canonical ATG start codon is essential for Aα-chain translation and hence fibrinogen synthesis. PCR amplification and Sanger sequencing of all FGA exons; compound heterozygosity with FGA c.385C>T (R129X) in a patient with afibrinogenemia Blood coagulation & fibrinolysis Medium 22732251

Source papers

Stage 0 corpus · 111 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1999 Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature genetics 1381 10391209
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1984 Fibrinogen and fibrin. Annual review of biochemistry 600 6383194
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2002 Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. The New England journal of medicine 451 12050338
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2012 Secreted kinase phosphorylates extracellular proteins that regulate biomineralization. Science (New York, N.Y.) 365 22582013
1997 Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin. Nature 360 9333233
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
1993 Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1-dependent pathway. Cell 315 8100742
1980 Studies on synthetic peptides that bind to fibrinogen and prevent fibrin polymerization. Structural requirements, number of binding sites, and species differences. Biochemistry 294 7356959
2015 A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell 270 26091039
2006 p130Cas: a versatile scaffold in signaling networks. Trends in cell biology 266 16581250
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2009 Crystal structure of human fibrinogen. Biochemistry 258 19296670
2004 An investigation into the human serum "interactome". Electrophoresis 247 15174051
1968 Fibrinogen Detroit--a molecular defect in the N-terminal disulphide knot of human fibrinogen? Nature 224 5645286
1999 Fibrinogen. The international journal of biochemistry & cell biology 223 10467729
1999 Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia. The Journal of clinical investigation 85 9916133
2001 Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes. Human genetics 62 11354637
2002 Outcome of donor splice site mutations accounting for congenital afibrinogenemia reflects order of intron removal in the fibrinogen alpha gene (FGA). Blood 41 12406899
2022 FGA Controls VEGFA Secretion to Promote Angiogenesis by Activating the VEGFR2-FAK Signalling Pathway. Frontiers in endocrinology 40 35498401
2018 Identification of serum proteins AHSG, FGA and APOA-I as diagnostic biomarkers for gastric cancer. Clinical proteomics 40 29719494
2000 A Korean population study of the nine STR loci FGA, VWA, D3S1358, D18S51, D21S11, D8S1179, D7S820, D13S317 and D5S818. International journal of legal medicine 38 11197626
2001 Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G-->T. Blood 36 11238133
2014 Targeted mutation of zebrafish fga models human congenital afibrinogenemia. Blood 29 24553182
2022 Hypofibrinogenemia with preserved hemostasis and protection from thrombosis in mice with an Fga truncation mutation. Blood 24 34905618
2020 Serum sCD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics. Journal of cellular and molecular medicine 22 32967043
1999 The 11 kb FGA deletion responsible for congenital afibrinogenaemia is mediated by a short direct repeat in the fibrinogen gene cluster. European journal of human genetics : EJHG 22 10602365
2005 Functional polymorphisms of FGA, encoding alpha fibrinogen, are associated with susceptibility to venous thromboembolism in a Taiwanese population. Human genetics 21 16362348
1997 Report of the European DNA profiling group (EDNAP): an investigation of the complex STR loci D21S11 and HUMFIBRA (FGA). Forensic science international 20 9153779
2016 Familial mutations in fibrinogen Aα (FGA) chain identified in renal amyloidosis increase in vitro amyloidogenicity of FGA fragment. Biochimie 19 27126074
2022 FGA inhibits metastases and induces autophagic cell death in gastric cancer via inhibiting ITGA5 to regulate the FAK/ERK pathway. Tissue & cell 15 35257941
2016 Ischemic Stroke and Six Genetic Variants in CRP, EPHX2, FGA, and NOTCH3 Genes: A Meta-Analysis. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 13 27266621
2012 A novel regulatory element between the human FGA and FGG genes. Thrombosis and haemostasis 13 22836734
2007 A single mutation in the FGA locus responsible for false homozygosities and discrepancies between commercial kits in an unusual paternity test case. Journal of forensic sciences 13 17316238
2019 FGA isoform as an indicator of targeted therapy for EGFR mutated lung adenocarcinoma. Journal of molecular medicine (Berlin, Germany) 12 31776635
2024 FGA influences invasion and metastasis of hepatocellular carcinoma through the PI3K/AKT pathway. Aging 11 39227068
2022 Serum Proteomic Analysis Identifies SAA1, FGA, SAP, and CETP as New Biomarkers for Eosinophilic Granulomatosis With Polyangiitis. Frontiers in immunology 11 35757752
2015 Hepatic Fibrinogen Storage Disease in a Patient with Hypofibrinogenemia: Report of a Case with a Missense Mutation of the FGA Gene. Seminars in liver disease 11 26676819
2004 Accurate STR allele designations at the FGA and vWA loci despite primer site polymorphisms. Journal of forensic sciences 11 15027538
2017 A Chinese family with congenital Dysfibrinogenemia carries a heterozygous missense mutation in FGA: Concerning the genetic abnormality and clinical treatment. Pakistan journal of medical sciences 10 29067075
2011 A novel frameshift mutation in FGA (c.1846 del A) leading to congenital afibrinogenemia in a consanguineous Syrian family. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 10 21245743
2010 Identification and functional characterization of a novel nonsense mutation in FGA accounting for congenital afibrinogenemia in six Egyptian patients. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 9 20051841
2013 siRNA down-regulation of FGA mRNA in HepG2 cells demonstrated that heterozygous abnormality of the Aα-chain gene does not affect the plasma fibrinogen level. Thrombosis research 8 23414568
2012 Mutation of the translation initiation codon in FGA causes congenital afibrinogenemia. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 8 22732251
2006 Identification of three FGA mutations in two Chinese families with congenital afibrinogenaemia. Haemophilia : the official journal of the World Federation of Hemophilia 8 17083511
2017 Heterozygous FGA p.Asp473Ter (fibrinogen Nieuwegein) presenting as antepartum cerebral thrombosis. Thrombosis research 7 29122299
2009 A novel frameshift mutation in FGA accounting for congenital afibrinogenemia predicted to encode an aberrant peptide terminating 158 amino acids downstream. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 7 19417632
1999 Genetic data on three complex STRs (ACTBP2, D21S11 and HUMFIBRA/FGA) in the Galician population (NW Spain). International journal of legal medicine 7 10460432
1998 Population genetic characteristics of the STR Loci D21S11 and FGA in eight diverse human populations. Human biology 7 9780514
2023 Association between FGA gene polymorphisms and coronary artery lesion in Kawasaki disease. Frontiers in medicine 6 37575991
2023 Factor VII R353Q (rs6046), FGA A6534G (rs6050), and FGG C10034T (rs2066865) Gene Polymorphisms and Risk of Recurrent Pregnancy Loss in Iranian Women. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 6 38708173
2010 Identification of dual false indirect exclusions on the D5S818 and FGA loci. Legal medicine (Tokyo, Japan) 6 21030286
2004 Sexual differentiation traits in functional males with female genital apertures (male symbol fga) in the woodlice Armadillidium vulgare Latr. (Isopoda, Crustacea). General and comparative endocrinology 6 15242750
2020 Analysis of an Inherited Dysfibrinogenemia Pedigree Associated with a Heterozygous Mutation in the FGA Gene. Hamostaseologie 5 33374030
2016 Dysfibrinogenemia-associated novel heterozygous mutation, Shanghai (FGA c.169_180+2 del), leads to N-terminal truncation of fibrinogen Aα chain and impairs fibrin polymerization. Journal of clinical pathology 5 27555433
2014 In vitro rescue of FGA deletion by lentiviral transduction of an afibrinogenemic patient's hepatocytes. Journal of thrombosis and haemostasis : JTH 5 25163824
2005 A novel nonsense mutation in the FGA gene in a Chinese family with congenital afibrinogenaemia. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 5 15795544
2018 A novel fibrinogen variant in a Chinese pedigree with congenital dysfibrinogenemia caused by FGA P. Arg38Thr mutation: A case report. Medicine 4 30290666
2015 Multistep microsatellite mutation leading to father-child mismatch of FGA locus in a case of non-exclusion parentage. Legal medicine (Tokyo, Japan) 4 25979606
2013 Association of the FGA and SLC6A4 genes with autistic spectrum disorder in a Korean population. Neuropsychobiology 4 24192574
1998 The short tandem repeat loci hTPO, THO1 and FGA. Human heredity 4 9813453
2024 Glycerophosphoinositol modulates FGA and NOTCH3 in exercise-induced muscle adaptation and colon cancer progression. Frontiers in pharmacology 3 39130639
2022 A Case of Type 1 Triallelic Patterns at D5S818, D18S51, D6S1043, and FGA Demonstrated by Short Tandem Repeat Analysis. International journal of clinical practice 3 35685547
2020 A Novel Frameshift Mutation in the FGA Gene (c.196 delT) Leading to Congenital Afibrinogenemia. Journal of pediatric hematology/oncology 3 31725541
2012 Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238 bp deletion, and a compound heterozygous FGA1238 bp deletion and novel FGA c.54+3A>C substitution. International journal of hematology 3 22639050
2023 Germline VWF/MPRIP and somatoplasm FGA variants synergically confer susceptibility to non-traumatic osteonecrosis of the femoral head. Scientific reports 2 36813871
2023 Selective vitamins as potential options for dietary therapeutic interventions: In silico and In vitro insights from mutant C terminal fragment of FGA. The Journal of steroid biochemistry and molecular biology 2 36907427
2022 Positron Emission Tomography (PET) with 18F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model. Molecular imaging 2 35250392
2021 An FGA Frameshift Variant Associated with Afibrinogenemia in Dachshunds. Genes 2 34356081
2019 c.259A>C in the fibrinogen gene of alpha chain (FGA) is a fibrinogen with thrombotic phenotype. The application of clinical genetics 2 30881084
2019 The Relationship between Gene Polymorphism of miRNAs Regulating FGA and Schizophrenia. Open access Macedonian journal of medical sciences 2 31198450
2017 A novel fibrinogen mutation: FGA g. 3057 C > T (p. Arg104 > Cys) impairs fibrinogen secretion. BMC hematology 2 29299315
2016 Population database on: D1S1656, D2S441, D2S1338, D3S1358, D8S1179, D10S1248, D22S1045, D12S391, D16S539, D18S51, D19S433, D21S11, FGA, TH01, vWA loci included in NGM system based on one thousand unrelated individuals from Lodz region of Central Poland. Archiwum medycyny sadowej i kryminologii 2 28144929
2012 A hypervariable STR polymorphism in the CFI gene: mutation rate and no linkage disequilibrium with FGA. Legal medicine (Tokyo, Japan) 2 23201233
2025 FGA, a new target of histone acetylation, inhibits apoptosis of granulosa cells in follicles. Biological research 1 40605115
2020 Congenital fibrinogen disorder caused by digenic mutations of the FGA and FGB genes. Hematology (Amsterdam, Netherlands) 1 32228225
2020 Population-dependent migration shift caused by sequence variation at the alpha fibrinogen (FGA) short tandem repeat (STR) locus. Forensic science international 1 32659604
2020 A family study of congenital dysfibrinogenemia caused by a novel mutation in the FGA gene: A case report. Open medicine (Warsaw, Poland) 1 33336034
2019 [Analysis of a pedigree affected with congenital dysfibrinogenemia due to a novel Gly31Glu mutation of FGA gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 31515786
2015 Concurrent copy number variations on chromosome 8 and 22 combined with mutation at FGA locus revealed in a parentage testing case. Forensic science international. Genetics 1 26186693
2014 Analysis of positive control STR experiments reveals that results obtained for FGA, D3S1358, and D13S317 condition the success rate of the analysis of routine reference samples. Journal of forensic sciences 1 24605994
2009 [Genetic analysis of an inherited afibrinogenemia family caused by a novel frameshift mutation in FGA]. Zhongguo shi yan xue ye xue za zhi 1 19698251
2007 Allele frequencies for nine STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820) in the Italian population. Forensic science international 1 17349757
2005 [Congenital afibrinogenemia associated with a novel nonsense mutation in the FGA gene]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 1 15946522
2026 Congenital hypofibrinogenemia with bleeding risk: mutations in the FGA, FGB, and FGG genes. Laboratory medicine 0 41233956
2026 FGA Serves as a Potential Diagnostic Marker and Therapeutic Target for Elderly Acute Kidney Injury. Journal of proteome research 0 41512179
2026 Immunosuppressive Pulse Therapy Alleviates Ocular Surface Damage in Thyroid-Associated Ophthalmopathy by Reversing FGA Deficiency Subsequently Modulating Complement and Coagulation Cascade Signaling to Suppress Orbital Fibroblast Pathology. Immunological investigations 0 41741162
2025 FGA can be used as a promising therapeutic target in osteoarthritis. BMC musculoskeletal disorders 0 40394574
2025 Proteomic Profiling Reveals TPR and FGA as Predictive Serum Biomarkers of Relapse to First- and Second-Generation EGFR-TKIs in Advanced Lung Adenocarcinoma. Biomedicines 0 40722683
2017 [Genetic Analysis of A Case of Congenital Dysfibrinogenemia Caused by Arg16His Mutation in Exon 2 of FGA]. Zhongguo shi yan xue ye xue za zhi 0 29070135
2013 [Identification of a rare allele FGA-13 in Guangdong Han population]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 24327161
2010 [Negative association of FGA gene 128C/G polymorphism with cerebral infarction and its effect on plasma fibrinogen in Hunan Hans]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 20533267
2008 [Identification of a rare allele of FGA-13]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 19065534
2004 Population studies for STR loci (D3S1358, D5S818, D7S820, D18S51 and FGA) in NWFP and Sindhi populations of Pakistan for forensic use. Archiwum medycyny sadowej i kryminologii 0 15782779
2001 [Genetic studies in the Cologne administrative district (North Rhine-Westphalia, Germany): DNA-STR systems FGA, TH01, VWA and YNZ22]. Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur 0 11591050
1999 DNA-PCR system FGA (FIBRA)--genotype and allele frequencies in a sample of western Germany (Düsseldorf region). Collegium antropologicum 0 10646230
1999 [Study of the high polymorphism STR locus-FGA in Chinese population]. Fa yi xue za zhi 0 12536389