FGA (fibrinogen alpha chain)

Gene

• Entrez ID: 2243
• Gene name: Fibrinogen alpha chain
• Gene symbol: FGA
• Synonyms (NCBI Gene): AMYLD2, Fib2
• Chromosome: 4
• Chromosome location: 4q31.3
• Summary: This gene encodes the alpha subunit of the coagulation factor fibrinogen, which is a component of the blood clot. Following vascular injury, the encoded preproprotein is proteolytically processed by thrombin during the conversion of fibrinogen to fibrin.

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs6050	T>A,C	Benign, risk-factor	Coding sequence variant, missense variant
rs78506343	C>A,G,T	Pathogenic	Missense variant, coding sequence variant
rs121909606	G>A,T	Pathogenic	Missense variant, coding sequence variant
rs121909607	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs121909608	T>C	Other, likely-pathogenic	Missense variant, coding sequence variant
rs121909612	T>A	Pathogenic	Missense variant, coding sequence variant
rs140911890	G>A,T	Likely-pathogenic	Synonymous variant, stop gained, coding sequence variant
rs146387238	C>A,G	Pathogenic	Splice donor variant
rs587777761	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs587777762	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs606231225	->A	Pathogenic	Stop gained, coding sequence variant
rs755117226	G>A	Pathogenic	Coding sequence variant, stop gained
rs762964798	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs776817952	G>A,T	Likely-pathogenic	Stop gained, coding sequence variant, synonymous variant
rs1214070111	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs1578795296	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1578795880	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1578796476	G>A	Pathogenic	Coding sequence variant, stop gained
rs1578798730	AATTTCCATTA>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005518	hsa-miR-409-3p	ELISA, Flow, Luciferase reporter assay	20570858
MIRT005527	hsa-miR-29c-3p	Luciferase reporter assay	20570858
MIRT005529	hsa-miR-144-3p	Luciferase reporter assay	20570858
MIRT005531	hsa-miR-29a-3p	Luciferase reporter assay	20570858
MIRT005533	hsa-miR-29b-3p	Luciferase reporter assay	20570858
MIRT005527	hsa-miR-29c-3p	Luciferase reporter assay	20570858
MIRT995087	hsa-miR-101	CLIP-seq
MIRT995088	hsa-miR-105	CLIP-seq
MIRT995089	hsa-miR-1261	CLIP-seq
MIRT995090	hsa-miR-1262	CLIP-seq
MIRT995091	hsa-miR-1290	CLIP-seq
MIRT995092	hsa-miR-1293	CLIP-seq
MIRT995093	hsa-miR-1343	CLIP-seq
MIRT995094	hsa-miR-216a	CLIP-seq
MIRT995095	hsa-miR-2467-3p	CLIP-seq
MIRT995096	hsa-miR-29a	CLIP-seq
MIRT995097	hsa-miR-29b	CLIP-seq
MIRT995098	hsa-miR-29c	CLIP-seq
MIRT995099	hsa-miR-3123	CLIP-seq
MIRT995100	hsa-miR-3167	CLIP-seq
MIRT995101	hsa-miR-3667-3p	CLIP-seq
MIRT995102	hsa-miR-3671	CLIP-seq
MIRT995103	hsa-miR-3674	CLIP-seq
MIRT995104	hsa-miR-3678-3p	CLIP-seq
MIRT995105	hsa-miR-3690	CLIP-seq
MIRT995106	hsa-miR-3925-5p	CLIP-seq
MIRT995107	hsa-miR-4254	CLIP-seq
MIRT995108	hsa-miR-4483	CLIP-seq
MIRT995109	hsa-miR-4694-3p	CLIP-seq
MIRT995110	hsa-miR-4701-3p	CLIP-seq
MIRT995111	hsa-miR-4724-3p	CLIP-seq
MIRT995112	hsa-miR-4732-5p	CLIP-seq
MIRT995113	hsa-miR-4747-5p	CLIP-seq
MIRT995114	hsa-miR-4761-5p	CLIP-seq
MIRT995115	hsa-miR-4762-5p	CLIP-seq
MIRT995116	hsa-miR-520d-5p	CLIP-seq
MIRT995117	hsa-miR-524-5p	CLIP-seq
MIRT995118	hsa-miR-548p	CLIP-seq
MIRT995119	hsa-miR-607	CLIP-seq
MIRT995120	hsa-miR-876-5p	CLIP-seq
MIRT995116	hsa-miR-520d-5p	CLIP-seq
MIRT995117	hsa-miR-524-5p	CLIP-seq
MIRT2229152	hsa-miR-1292	CLIP-seq
MIRT2229153	hsa-miR-141	CLIP-seq
MIRT2229154	hsa-miR-200a	CLIP-seq
MIRT2229155	hsa-miR-4471	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
TFCP2	Unknown	10455131

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002250	Process	Adaptive immune response	IEA
GO:0002376	Process	Immune system process	IEA
GO:0005102	Function	Signaling receptor binding	IDA	10903502
GO:0005102	Function	Signaling receptor binding	IEA
GO:0005198	Function	Structural molecule activity	IDA	8910396
GO:0005198	Function	Structural molecule activity	IMP	10891444
GO:0005201	Function	Extracellular matrix structural constituent	HDA	28344315
GO:0005201	Function	Extracellular matrix structural constituent	RCA	25037231, 28675934
GO:0005515	Function	Protein binding	IPI	10954706, 12706644, 22582013, 26091039, 28514442, 32296183, 32814053, 33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005577	Component	Fibrinogen complex	IBA
GO:0005577	Component	Fibrinogen complex	IDA	8910396, 16846481, 18676163
GO:0005577	Component	Fibrinogen complex	IEA
GO:0005577	Component	Fibrinogen complex	TAS	10467729
GO:0005615	Component	Extracellular space	IDA	6777381
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0007160	Process	Cell-matrix adhesion	IDA	10903502
GO:0007596	Process	Blood coagulation	IEA
GO:0007599	Process	Hemostasis	IEA
GO:0009897	Component	External side of plasma membrane	IDA	6777381
GO:0009897	Component	External side of plasma membrane	IEA
GO:0009986	Component	Cell surface	IDA	6777381
GO:0030168	Process	Platelet activation	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	IBA
GO:0031012	Component	Extracellular matrix	HDA	25037231, 28344315, 28675934
GO:0031091	Component	Platelet alpha granule	IDA	6777381
GO:0031093	Component	Platelet alpha granule lumen	IEA
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0031639	Process	Plasminogen activation	IDA	16846481
GO:0031639	Process	Plasminogen activation	IEA
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IBA
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IDA	8100742
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IEA
GO:0042730	Process	Fibrinolysis	IBA
GO:0042730	Process	Fibrinolysis	IDA	16846481
GO:0042730	Process	Fibrinolysis	IEA
GO:0043152	Process	Induction of bacterial agglutination	IDA	24367264
GO:0045087	Process	Innate immune response	IEA
GO:0045907	Process	Positive regulation of vasoconstriction	IDA	15739255
GO:0045907	Process	Positive regulation of vasoconstriction	IEA
GO:0045921	Process	Positive regulation of exocytosis	IDA	19193866
GO:0046872	Function	Metal ion binding	IEA
GO:0050714	Process	Positive regulation of protein secretion	IDA	19193866
GO:0050714	Process	Positive regulation of protein secretion	IEA
GO:0050839	Function	Cell adhesion molecule binding	IDA	9182580
GO:0051258	Process	Protein polymerization	IDA	12706644
GO:0051258	Process	Protein polymerization	IEA
GO:0051592	Process	Response to calcium ion	IDA	6777381
GO:0051592	Process	Response to calcium ion	IEA
GO:0065003	Process	Protein-containing complex assembly	IDA	8910396
GO:0065003	Process	Protein-containing complex assembly	IMP	18676163
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IDA	10903502, 19193866
GO:0070527	Process	Platelet aggregation	HMP	23382103
GO:0070527	Process	Platelet aggregation	IBA
GO:0070527	Process	Platelet aggregation	IDA	6281794
GO:0070527	Process	Platelet aggregation	IEA
GO:0072377	Process	Blood coagulation, common pathway	IBA
GO:0072377	Process	Blood coagulation, common pathway	IMP	10891444, 12706644
GO:0072378	Process	Blood coagulation, fibrin clot formation	IDA	16846481
GO:0072378	Process	Blood coagulation, fibrin clot formation	IEA
GO:0072562	Component	Blood microparticle	HDA	22516433
GO:0090277	Process	Positive regulation of peptide hormone secretion	IDA	19193866
GO:0090277	Process	Positive regulation of peptide hormone secretion	IEA
GO:1900026	Process	Positive regulation of substrate adhesion-dependent cell spreading	NAS	24041635
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IDA	10903502
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IEA
GO:1903561	Component	Extracellular vesicle	HDA	24769233
GO:2000261	Process	Negative regulation of blood coagulation, common pathway	TAS	11529842
GO:2000352	Process	Negative regulation of endothelial cell apoptotic process	IDA	10903502
GO:2000352	Process	Negative regulation of endothelial cell apoptotic process	IEA

Other IDs

• MIM: 134820
• HGNC: 3661
• e!Ensembl: ENSG00000171560

Protein

• UniProt ID: P02671
• Protein name: Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain]
• Protein function: Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components o
• PDB: 1BBR, 1DM4, 1FPH, 1FZA, 1FZB, 1FZC, 1FZD, 1FZE, 1FZF, 1FZG, 1LT9, 1LTJ, 1N86, 1N8E, 1RE3, 1RE4, 1RF0, 1RF1, 1YCP, 2A45, 2FFD, 2H43, 2HLO, 2HOD, 2HPC, 2OYH, 2OYI, 2Q9I, 2XNX, 2XNY, 2Z4E, 3AT0, 3BVH, 3E1I, 3GHG, 3H32, 3HUS, 4F27, 5CFA
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08702	Fib_alpha	49 → 191	Fibrinogen alpha/beta chain family	Coiled-coil
  PF12160	Fibrinogen_aC	445 → 509	Fibrinogen alpha C domain	Domain
  PF00147	Fibrinogen_C	628 → 863	Fibrinogen beta and gamma chains, C-terminal globular domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in blood plasma (at protein level). {ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725}.
• Sequence:

  MFSMRIVCLVLSVVGTAWTADSGEGDFLAEGGGVRGPRVVERHQSACKDSDWPFCSDEDW
  NYKCPSGCRMKGLIDEVNQDFTNRINKLKNSLFEYQKNNKDSHSLTTNIMEILRGDFSSA
  NNRDNTYNRVSEDLRSRIEVLKRKVIEKVQHIQLLQKNVRAQLVDMKRLEVDIDIKIRSC
  RGSCSRALAREVDLKDYEDQQKQLEQVIAKDLLPSRDRQHLPLIKMKPVPDLVPGNFKSQ
  LQKVPPEWKALTDMPQMRMELERPGGNEITRGGSTSYGTGSETESPRNPSSAGSWNSGSS
  GPGSTGNRNPGSSGTGGTATWKPGSSGPGSTGSWNSGSSGTGSTGNQNPGSPRPGSTGTW
  NPGSSERGSAGHWTSESSVSGSTGQWHSESGSFRPDSPGSGNARPNNPDWGTFEEVSGNV
  SPGTRREYHTEKLVTSKGDKELRTGKEKVTSGSTTTTRRSCSKTVTKTVIGPDGHKEVTK
  EVVTSEDGSDCPEAMDLGTLSGIGTLDGFRHRHPDEAAFFDTASTGKTFPGFFSPMLGEF
  VSETESRGSESGIFTNTKESSSHHPGIAEFPSRGKSSSYSKQFTSSTSYNRGDSTFESKS
  YKMADEAGSEADHEGTHSTKRGHAKSRPVRDCDDVLQTHPSGTQSGIFNIKLPGSSKIFS
  VYCDQETSLGGWLLIQQRMDGSLNFNRTWQDYKRGFGSLNDEGEGEFWLGNDYLHLLTQR
  GSVLRVELEDWAGNEAYAEYHFRVGSEAEGYALQVSSYEGTAGDALIEGSVEEGAEYTSH
  NNMQFSTFDRDADQWEENCAEVYGGGWWYNNCQAANLNGIYYPGGSYDPRNNSPYEIENG
  VVWVSFRGADYSLRAVRMKIRPLVTQ

• Sequence length: 866

Pathways

KEGG:

Complement and coagulation cascades
Platelet activation
Neutrophil extracellular trap formation
Coronavirus disease - COVID-19

Reactome:

Platelet degranulation
Common Pathway of Fibrin Clot Formation
Integrin cell surface interactions
Integrin signaling
GRB2:SOS provides linkage to MAPK signaling for Integrins
p130Cas linkage to MAPK signaling for integrins
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
MAP2K and MAPK activation
Regulation of TLR by endogenous ligand
Signaling by moderate kinase activity BRAF mutants
Signaling by high-kinase activity BRAF mutants
Signaling by BRAF and RAF fusions
Paradoxical activation of RAF signaling by kinase inactive BRAF
Post-translational protein phosphorylation
Signaling downstream of RAS mutants
Amyloid fiber formation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Abnormal bleeding	Pathogenic	rs121909607	RCV000851971
Afibrinogenemia	Likely pathogenic; Pathogenic	rs1299596156	RCV002245493
Congenital afibrinogenemia	Pathogenic; Likely pathogenic	rs2110806028, rs778779380, rs1299596156, rs763715993, rs2530823524, rs2530820376, rs121909607, rs121909612, rs121909613, rs146387238, rs606231225, rs755117226, rs776817952, rs762964798, rs140911890, rs1578796476	RCV001420405 RCV002506823 RCV005032194 RCV005225596 RCV004785730 RCV005036830 RCV002476987 RCV002490381 RCV002490382 RCV000017877 RCV000017879 RCV000454272 RCV002500996 RCV005029421 RCV002487602 RCV000984799
Congenital factor V deficiency	Likely pathogenic; Pathogenic	rs773619297	RCV005860257
Deep venous thrombosis	Likely pathogenic	rs121909613	RCV002222001
Dysfibrinogenemia	Likely pathogenic; Pathogenic	rs121909606, rs121909607	RCV000017825 RCV000030941
Familial dysfibrinogenemia	Likely pathogenic; Pathogenic	rs778779380, rs773619297, rs1299596156, rs763715993, rs745804153, rs2530819182, rs2530820376, rs121909606, rs121909607, rs121909612, rs121909613, rs146387238, rs755117226, rs776817952, rs762964798, rs140911890, rs1184440187	RCV002506823 RCV005868356 RCV005032194 RCV002266520 RCV002283365 RCV003313877 RCV005036830 RCV003330394 RCV002228034 RCV002490381 RCV002490382 RCV004700245 RCV002502594 RCV002500996 RCV002067219 RCV002487602 RCV005418812
Familial hypodysfibrinogenemia	Pathogenic	rs146387238	RCV000030942
Familial visceral amyloidosis, Ostertag type	Likely pathogenic; Pathogenic	rs778779380, rs773619297, rs1302701490, rs1299596156, rs2530823524, rs2530820376, rs121909607, rs587777761, rs121909612, rs121909613, rs587777762, rs146387238, rs755117226, rs776817952, rs762964798, rs140911890	RCV002506823 RCV006249766 RCV001808895 RCV005032194 RCV002466823 RCV005036830 RCV002476987 RCV000017870 RCV000017871 RCV002490382 RCV000017875 RCV002496394 RCV002502594 RCV002500996 RCV005029421 RCV002487602
FGA-related disorder	Pathogenic; Likely pathogenic	rs2530820233, rs2530822869, rs2530830192, rs121909606, rs121909608, rs121909607, rs762964798, rs140911890	RCV004528651 RCV004531662 RCV004534409 RCV004532378 RCV004734521 RCV004532379 RCV004735797 RCV000779434
FIBRINOGEN AARHUS 1	Likely pathogenic	rs121909608	RCV000017843
FIBRINOGEN CANTERBURY	Pathogenic	rs121909614	RCV000017874
FIBRINOGEN DETROIT 1	Likely pathogenic	rs1403508334	RCV000017842
FIBRINOGEN DUSART	Likely pathogenic	rs121909613	RCV000017872
Hypofibrinogenemia	Likely pathogenic; Pathogenic	rs121909608, rs121909607, rs146387238, rs1578795296, rs1214070111, rs776817952, rs762964798, rs121909606	RCV000851993 RCV000851581 RCV000851811 RCV000852035 RCV000851912 RCV000852248 RCV000852003 RCV000851972 RCV000851968
See cases	Likely pathogenic	rs778571941	RCV002287813

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
AFib amyloidosis	Uncertain significance	rs771023837	RCV000627058
FIBRINOGEN CARACAS 2	Uncertain significance	rs121909610	RCV000017865
FIBRINOGEN KEOKUK	other	rs121909615	RCV000017880
FIBRINOGEN KYOTO 2	other	rs121909609	RCV000017844
FIBRINOGEN LILLE 1	other	rs121909604	RCV000017823
FIBRINOGEN MARBURG	other	rs121909611	RCV000017867
FIBRINOGEN MUNICH 1	other	rs2530830204	RCV000017841
FIBRINOGEN NIEUWEGEIN	other	rs2530820495	RCV000017878
FIBRINOGEN ROUEN 1	Conflicting classifications of pathogenicity	rs121909605	RCV000017824
Thrombocytopenia	Benign; Likely benign	rs2070031	RCV001270514
Venous thromboembolism, susceptibility to	Benign	rs6050	RCV000017882

Associations from Text Mining
Disease Name	Relationship Type	References
Abortion Spontaneous	Associate	26139837
Adenocarcinoma of Lung	Associate	39940778, 40179422
Afibrinogenemia	Associate	10891444, 17854317, 25163824, 26139837, 26676819, 29240685, 32228225, 9916133
Alzheimer Disease	Associate	40471493
Amyloidosis	Associate	29455155
Amyloidosis Familial	Associate	29240685, 29455155
Amyotrophic Lateral Sclerosis	Associate	39278909
Asthma	Associate	35757752
Axial Spondyloarthritis	Associate	33317138
Blood Coagulation Disorders	Associate	36471393, 36507906
Carcinoma Hepatocellular	Associate	25789864
Carcinoma Squamous Cell	Associate	37839873, 37841237, 39354528, 40179422
Cardiomyopathy Dilated	Associate	29540862
Cerebral Hemorrhage	Associate	33186848
Cerebral Infarction	Associate	18331453, 19143925
Cognitive Dysfunction	Associate	26581183
Colonic Polyps	Associate	30361067
Colorectal Neoplasms	Associate	30361067
Corneal Dystrophy Fleck	Associate	32228225
Coronary Artery Disease	Associate	20167083, 26908601, 33299376
Craniocerebral Trauma	Associate	36813871
Death	Associate	39354528
Disseminated Intravascular Coagulation	Associate	36813871
Dysfibrinogenemia Congenital	Associate	26581183, 29240685, 30290666, 32228225
Femur Head Necrosis	Associate	36813871
Graft vs Host Disease	Associate	34269649
Granuloma Annulare	Associate	37353960
Granulomatosis with Polyangiitis	Stimulate	35757752
Heart Diseases	Associate	32174066
Hemoptysis	Associate	33186848
Hepatitis C	Associate	25789864
Hypertension	Associate	27553289
Hypothyroidism	Associate	29301248
Idiopathic Noncirrhotic Portal Hypertension	Associate	34052252
IgA Vasculitis	Associate	36796721
Intracranial Thrombosis	Associate	37175682
Keratoconus	Inhibit	24194634
Kidney Calculi	Stimulate	40253023
Leukemia Myeloid Acute	Associate	33284559
Lymphatic Metastasis	Associate	37839873
Lysosomal Storage Diseases	Associate	26676819
Melhem Fahl syndrome	Associate	39625198
Myocardial Infarction	Associate	18772067
Myotonic Dystrophy	Associate	36507906
Neoplastic Syndromes Hereditary	Inhibit	29769041
Osteoarthritis	Associate	39684216
Pemphigus	Associate	39593117
Pulmonary Embolism	Associate	37442158
Retinal Vein Occlusion	Associate	19515723, 36820679
Silicosis	Associate	27803925
Squamous Cell Carcinoma of Head and Neck	Stimulate	31253657
Stomach Neoplasms	Associate	30106150, 36842141
Stomach Neoplasms	Inhibit	33788653
Stroke	Associate	26908601
Thromboembolism	Associate	19515723
Thrombophilia	Associate	26139837, 26581183
Thrombosis	Associate	32299226, 36028558, 36813871
Urachal Cyst	Associate	12492584
Uterine Cervical Neoplasms	Associate	30625128
Venous Thromboembolism	Associate	26581183, 26908601
Venous Thromboembolism	Inhibit	33834859
Venous Thrombosis	Associate	22353194, 26982741, 30168256