Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE4DJ79)

• DOT Name: Tetraspanin-7 (TSPAN7)
• Synonyms: Tspan-7; Cell surface glycoprotein A15; Membrane component chromosome X surface marker 1; T-cell acute lymphoblastic leukemia-associated antigen 1; TALLA-1; Transmembrane 4 superfamily member 2; CD antigen CD231
• Gene Name: TSPAN7
• Related Disease:
  Intellectual disability, X-linked 58
  Non-syndromic X-linked intellectual disability
• UniProt ID: TSN7_HUMAN
• Pfam ID: PF00335
• Sequence:
  MASRRMETKPVITCLKTLLIIYSFVFWITGVILLAVGVWGKLTLGTYISLIAENSTNAPY
  VLIGTGTTIVVFGLFGCFATCRGSPWMLKLYAMFLSLVFLAELVAGISGFVFRHEIKDTF
  LRTYTDAMQTYNGNDERSRAVDHVQRSLSCCGVQNYTNWSTSPYFLEHGIPPSCCMNETD
  CNPQDLHNLTVAATKVNQKGCYDLVTSFMETNMGIIAGVAFGIAFSQLIGMLLACCLSRF
  ITANQYEMV
• Function: May be involved in cell proliferation and cell motility.
• Tissue Specificity: Not solely expressed in T-cells. Expressed in acute myelocytic leukemia cells of some patients.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway:
  Trafficking of GluR2-containing AMPA receptors (R-HSA-416993)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability, X-linked 58	DISRMLYX	Definitive	X-linked	[1]
Non-syndromic X-linked intellectual disability	DIS71AI3	Moderate	X-linked	[2]

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 Tetraspanin-7 (TSPAN7).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tetraspanin-7 (TSPAN7).	[13]

11 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-7 (TSPAN7).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Tetraspanin-7 (TSPAN7).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tetraspanin-7 (TSPAN7).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Tetraspanin-7 (TSPAN7).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tetraspanin-7 (TSPAN7).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tetraspanin-7 (TSPAN7).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tetraspanin-7 (TSPAN7).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tetraspanin-7 (TSPAN7).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tetraspanin-7 (TSPAN7).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Tetraspanin-7 (TSPAN7).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tetraspanin-7 (TSPAN7).	[14]

References

• [1] Nonsyndromic X-linked mental retardation: mapping of MRX58 to the pericentromeric region. Am J Med Genet. 1999 Sep 10;86(2):102-6. doi: 10.1002/(sici)1096-8628(19990910)86:2<102::aid-ajmg2>3.0.co;2-c.
• [2] 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.
• [3] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [13] 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.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.