Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMIHY80)

• DOT Name: Fibrinogen alpha chain (FGA)
• Gene Name: FGA
• Related Disease:
  Acute kidney injury
  Cerebral infarction
  Congenital afibrinogenemia
  Congenital fibrinogen deficiency
  Familial dysfibrinogenemia
  Amyloidosis
  Asthma
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cerebrovascular disease
  Cholestasis
  Colorectal carcinoma
  Endometriosis
  Familial visceral amyloidosis
  Gastric cancer
  Hereditary amyloidosis
  Lung adenocarcinoma
  Lung neoplasm
  Metabolic disorder
  Myocardial infarction
  Nephropathy
  Oral cavity squamous cell carcinoma
  Osteoporosis
  Pancreatitis
  Pervasive developmental disorder
  Psoriatic arthritis
  Pulmonary embolism
  Pulmonary hypertension
  Schizophrenia
  Stomach cancer
  Thrombocytopenia
  Thrombophilia
  Thrombosis
  Vascular disease
  High blood pressure
  Neuroblastoma
  Plasma cell myeloma
  Venous thromboembolism
  AFib amyloidosis
  Familial hypofibrinogenemia
  Acute liver failure
  Carcinoma of liver and intrahepatic biliary tract
  Cardiomyopathy
  Disseminated intravascular coagulation
  Liver cancer
  Lung cancer
  Lung carcinoma
  Nephrotic syndrome
• UniProt ID: FIBA_HUMAN
• PDB ID: 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
• Pfam ID: PF08702 ; PF12160 ; PF00147
• Sequence:
  MFSMRIVCLVLSVVGTAWTADSGEGDFLAEGGGVRGPRVVERHQSACKDSDWPFCSDEDW
  NYKCPSGCRMKGLIDEVNQDFTNRINKLKNSLFEYQKNNKDSHSLTTNIMEILRGDFSSA
  NNRDNTYNRVSEDLRSRIEVLKRKVIEKVQHIQLLQKNVRAQLVDMKRLEVDIDIKIRSC
  RGSCSRALAREVDLKDYEDQQKQLEQVIAKDLLPSRDRQHLPLIKMKPVPDLVPGNFKSQ
  LQKVPPEWKALTDMPQMRMELERPGGNEITRGGSTSYGTGSETESPRNPSSAGSWNSGSS
  GPGSTGNRNPGSSGTGGTATWKPGSSGPGSTGSWNSGSSGTGSTGNQNPGSPRPGSTGTW
  NPGSSERGSAGHWTSESSVSGSTGQWHSESGSFRPDSPGSGNARPNNPDWGTFEEVSGNV
  SPGTRREYHTEKLVTSKGDKELRTGKEKVTSGSTTTTRRSCSKTVTKTVIGPDGHKEVTK
  EVVTSEDGSDCPEAMDLGTLSGIGTLDGFRHRHPDEAAFFDTASTGKTFPGFFSPMLGEF
  VSETESRGSESGIFTNTKESSSHHPGIAEFPSRGKSSSYSKQFTSSTSYNRGDSTFESKS
  YKMADEAGSEADHEGTHSTKRGHAKSRPVRDCDDVLQTHPSGTQSGIFNIKLPGSSKIFS
  VYCDQETSLGGWLLIQQRMDGSLNFNRTWQDYKRGFGSLNDEGEGEFWLGNDYLHLLTQR
  GSVLRVELEDWAGNEAYAEYHFRVGSEAEGYALQVSSYEGTAGDALIEGSVEEGAEYTSH
  NNMQFSTFDRDADQWEENCAEVYGGGWWYNNCQAANLNGIYYPGGSYDPRNNSPYEIENG
  VVWVSFRGADYSLRAVRMKIRPLVTQ
• 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 of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways.
• Tissue Specificity: Detected in blood plasma (at protein level).
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  ER-Phagosome pathway (R-HSA-1236974)
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  MyD88 (R-HSA-166058)
  Integrin cell surface interactions (R-HSA-216083)
  Integrin signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  MAP2K and MAPK activation (R-HSA-5674135)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Amyloid fiber formation (R-HSA-977225)
  Platelet degranulation (R-HSA-114608)
• BioCyc Pathway: MetaCyc:ENSG00000171560-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute kidney injury	DISXZG0T	Definitive	Biomarker	[1]
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[2]
Congenital afibrinogenemia	DISGCW8D	Definitive	Autosomal recessive	[3]
Congenital fibrinogen deficiency	DIS84ZAR	Definitive	Semidominant	[4]
Familial dysfibrinogenemia	DISEOPCW	Definitive	Autosomal dominant	[3]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[5]
Asthma	DISW9QNS	Strong	Therapeutic	[6]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[9]
Cerebrovascular disease	DISAB237	Strong	Biomarker	[10]
Cholestasis	DISDJJWE	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Endometriosis	DISX1AG8	Strong	Altered Expression	[13]
Familial visceral amyloidosis	DIS7BVSW	Strong	Autosomal dominant	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[12]
Hereditary amyloidosis	DIS1GS6H	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[16]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[14]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[18]
Nephropathy	DISXWP4P	Strong	Biomarker	[15]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Biomarker	[19]
Osteoporosis	DISF2JE0	Strong	Biomarker	[20]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[21]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[22]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[23]
Pulmonary embolism	DISJYP9B	Strong	Biomarker	[24]
Pulmonary hypertension	DIS1RSP5	Strong	Genetic Variation	[25]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[26]
Stomach cancer	DISKIJSX	Strong	Biomarker	[12]
Thrombocytopenia	DISU61YW	Strong	Therapeutic	[27]
Thrombophilia	DISQR7U7	Strong	Autosomal dominant	[28]
Thrombosis	DIS2TXP8	Strong	Biomarker	[29]
Vascular disease	DISVS67S	Strong	Biomarker	[30]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[31]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[32]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[33]
Venous thromboembolism	DISUR7CR	moderate	Genetic Variation	[34]
AFib amyloidosis	DISSJZ33	Supportive	Autosomal dominant	[35]
Familial hypofibrinogenemia	DIS7WFBL	Supportive	Autosomal dominant	[36]
Acute liver failure	DIS5EZKX	Limited	Therapeutic	[37]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[38]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[39]
Disseminated intravascular coagulation	DISCAVOZ	Limited	Biomarker	[40]
Liver cancer	DISDE4BI	Limited	Biomarker	[38]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[38]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[38]
Nephrotic syndrome	DISSPSC2	Limited	Genetic Variation	[41]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fibrinogen alpha chain (FGA).	[42]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Fibrinogen alpha chain (FGA).	[47]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fibrinogen alpha chain (FGA).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fibrinogen alpha chain (FGA).	[44]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fibrinogen alpha chain (FGA).	[45]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibrinogen alpha chain (FGA).	[46]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fibrinogen alpha chain (FGA).	[43]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fibrinogen alpha chain (FGA).	[48]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Fibrinogen alpha chain (FGA).	[49]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Fibrinogen alpha chain (FGA).	[50]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fibrinogen alpha chain (FGA).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fibrinogen alpha chain (FGA).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Fibrinogen alpha chain (FGA).	[55]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Fibrinogen alpha chain (FGA).	[56]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Aspirin decreases the secretion of Fibrinogen alpha chain (FGA).	[51]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the cleavage of Fibrinogen alpha chain (FGA).	[52]
adenosine diphosphate	DMFUHKP	Investigative	adenosine diphosphate increases the secretion of Fibrinogen alpha chain (FGA).	[51]

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