Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA19OKO)

• DOT Name: Platelet glycoprotein IX (GP9)
• Synonyms: GP-IX; GPIX; Glycoprotein 9; CD antigen CD42a
• Gene Name: GP9
• Related Disease:
  Bernard-Soulier syndrome
  Autoimmune thrombocytopenia
  Barber-Say syndrome
  Brooke-Spiegler syndrome
  Coagulation defect
  Idiopathic thrombocytopenic purpura
  Immune thrombocytopenia
  Childhood myelodysplastic syndrome
  Myelodysplastic syndrome
  Stroke
  Inherited bleeding disorder, platelet-type
  Thrombocytopenia
• UniProt ID: GPIX_HUMAN
• PDB ID: 3REZ
• Pfam ID: PF13855 ; PF01462
• Sequence:
  MPAWGALFLLWATAEATKDCPSPCTCRALETMGLWVDCRGHGLTALPALPARTRHLLLAN
  NSLQSVPPGAFDHLPQLQTLDVTQNPWHCDCSLTYLRLWLEDRTPEALLQVRCASPSLAA
  HGPLGRLTGYQLGSCGWQLQASWVRPGVLWDVALVAVAALGLALLAGLLCATTEALD
• Function: The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis. GP-IX may provide for membrane insertion and orientation of GP-Ib.
• KEGG Pathway:
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway:
  GP1b-IX-V activation signalling (R-HSA-430116)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  Platelet Aggregation (Plug Formation) (R-HSA-76009)
  Defective F9 activation (R-HSA-9673221)
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bernard-Soulier syndrome	DISLD1FU	Definitive	Autosomal recessive	[1]
Autoimmune thrombocytopenia	DISNF0OI	Strong	Altered Expression	[2]
Barber-Say syndrome	DISW5MTJ	Strong	Biomarker	[3]
Brooke-Spiegler syndrome	DIS36OT6	Strong	Biomarker	[3]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[4]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Altered Expression	[2]
Immune thrombocytopenia	DISVCBNS	Strong	Altered Expression	[2]
Childhood myelodysplastic syndrome	DISMN80I	moderate	Biomarker	[5]
Myelodysplastic syndrome	DISYHNUI	moderate	Biomarker	[5]
Stroke	DISX6UHX	moderate	Genetic Variation	[6]
Inherited bleeding disorder, platelet-type	DISIUNXT	Limited	Biomarker	[7]
Thrombocytopenia	DISU61YW	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Platelet glycoprotein IX (GP9).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Platelet glycoprotein IX (GP9).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Platelet glycoprotein IX (GP9).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Platelet glycoprotein IX (GP9).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Platelet glycoprotein IX (GP9).	[12]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] A novel mutation in the GP1BA gene in Bernard-Soulier syndrome.Blood Coagul Fibrinolysis. 2020 Jan;31(1):83-86. doi: 10.1097/MBC.0000000000000868.
• [3] Bernard-Soulier syndrome.Haematologica. 2011 Mar;96(3):355-9. doi: 10.3324/haematol.2010.039883.
• [4] The same genetic defect in three Tunisian families with Bernard Soulier syndrome: a probable founder Stop mutation in GPIb.Ann Hematol. 2010 Jan;89(1):75-81. doi: 10.1007/s00277-009-0763-1. Epub 2009 May 30.
• [5] Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes.Haematologica. 2012 Jun;97(6):895-902. doi: 10.3324/haematol.2011.057158. Epub 2012 Jan 22.
• [6] Association of human platelet alloantigen 1 through 5 polymorphisms with ischemic stroke.Cerebrovasc Dis. 2008;25(1-2):81-6. doi: 10.1159/000111995. Epub 2007 Dec 6.
• [7] A large deletion in the GP9 gene in Cocker Spaniel dogs with Bernard-Soulier syndrome.PLoS One. 2019 Sep 4;14(9):e0220625. doi: 10.1371/journal.pone.0220625. eCollection 2019.
• [8] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.