Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8X0NWN)

• DOT Name: Tetraspanin-6 (TSPAN6)
• Synonyms: Tspan-6; A15 homolog; Putative NF-kappa-B-activating protein 321; T245 protein; Tetraspanin TM4-D; Transmembrane 4 superfamily member 6
• Gene Name: TSPAN6
• Related Disease:
  Developmental and epileptic encephalopathy, 9
  Intellectual disability
  Familial Alzheimer disease
• UniProt ID: TSN6_HUMAN
• Pfam ID: PF00335
• Sequence:
  MASPSRRLQTKPVITCFKSVLLIYTFIFWITGVILLAVGIWGKVSLENYFSLLNEKATNV
  PFVLIATGTVIILLGTFGCFATCRASAWMLKLYAMFLTLVFLVELVAAIVGFVFRHEIKN
  SFKNNYEKALKQYNSTGDYRSHAVDKIQNTLHCCGVTDYRDWTDTNYYSEKGFPKSCCKL
  EDCTPQRDADKVNNEGCFIKVMTIIESEMGVVAGISFGVACFQLIGIFLAYCLSRAITNN
  QYEIV

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy, 9	DISR0ACD	Definitive	Genetic Variation	[1]
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[1]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tetraspanin-6 (TSPAN6).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetraspanin-6 (TSPAN6).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tetraspanin-6 (TSPAN6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tetraspanin-6 (TSPAN6).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tetraspanin-6 (TSPAN6).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Tetraspanin-6 (TSPAN6).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Tetraspanin-6 (TSPAN6).	[9]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Tetraspanin-6 (TSPAN6).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Tetraspanin-6 (TSPAN6).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tetraspanin-6 (TSPAN6).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tetraspanin-6 (TSPAN6).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tetraspanin-6 (TSPAN6).	[13]

References

• [1] Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity.PLoS One. 2017 Feb 16;12(2):e0171968. doi: 10.1371/journal.pone.0171968. eCollection 2017.
• [2] Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments.Mol Neurodegener. 2017 Mar 10;12(1):25. doi: 10.1186/s13024-017-0165-0.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [11] Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: microarray gene expression analyses. Mutat Res. 2005 Dec 11;591(1-2):198-211.
• [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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.