Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3DI3NH)

• DOT Name: Tetraspanin-9 (TSPAN9)
• Synonyms: Tspan-9; Tetraspan NET-5
• Gene Name: TSPAN9
• Related Disease:
  Alphavirus infectious disease
  Myocardial infarction
  Coronary heart disease
  Metastatic malignant neoplasm
• UniProt ID: TSN9_HUMAN
• Pfam ID: PF00335
• Sequence:
  MARGCLCCLKYMMFLFNLIFWLCGCGLLGVGIWLSVSQGNFATFSPSFPSLSAANLVIAI
  GTIVMVTGFLGCLGAIKENKCLLLSFFIVLLVILLAELILLILFFVYMDKVNENAKKDLK
  EGLLLYHTENNVGLKNAWNIIQAEMRCCGVTDYTDWYPVLGENTVPDRCCMENSQGCGRN
  ATTPLWRTGCYEKVKMWFDDNKHVLGTVGMCILIMQILGMAFSMTLFQHIHRTGKKYDA
• Tissue Specificity: Expressed in megakaryocytes and platelets (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alphavirus infectious disease	DISZGSCJ	Strong	Biomarker	[1]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tetraspanin-9 (TSPAN9).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tetraspanin-9 (TSPAN9).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tetraspanin-9 (TSPAN9).	[11]

5 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 Tetraspanin-9 (TSPAN9).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tetraspanin-9 (TSPAN9).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tetraspanin-9 (TSPAN9).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tetraspanin-9 (TSPAN9).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Tetraspanin-9 (TSPAN9).	[12]

References

• [1] Role of TSPAN9 in Alphavirus Entry and Early Endosomes.J Virol. 2016 Apr 14;90(9):4289-97. doi: 10.1128/JVI.00018-16. Print 2016 May.
• [2] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [3] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [4] Tspan9 inhibits the proliferation, migration and invasion of human gastric cancer SGC7901 cells via the ERK1/2 pathway.Oncol Rep. 2016 Jul;36(1):448-54. doi: 10.3892/or.2016.4805. Epub 2016 May 13.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] 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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.