Details of Drug Off-Target (DOT)

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

• DOT Name: Tetraspanin-18 (TSPAN18)
• Synonyms: Tspan-18
• Gene Name: TSPAN18
• Related Disease:
  Advanced cancer
  Barrett esophagus
  Carcinoma of esophagus
  Esophageal adenocarcinoma
  Esophageal cancer
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obstructive sleep apnea
  Intellectual disability
  Schizophrenia
• UniProt ID: TSN18_HUMAN
• Pfam ID: PF00335
• Sequence:
  MEGDCLSCMKYLMFVFNFFIFLGGACLLAIGIWVMVDPTGFREIVAANPLLLTGAYILLA
  MGGLLFLLGFLGCCGAVRENKCLLLFFFLFILIIFLAELSAAILAFIFRENLTREFFTKE
  LTKHYQGNNDTDVFSATWNSVMITFGCCGVNGPEDFKFASVFRLLTLDSEEVPEACCRRE
  PQSRDGVLLSREECLLGRSLFLNKQGCYTVILNTFETYVYLAGALAIGVLAIELFAMIFA
  MCLFRGIQ
• Function: Plays a role in the cell surface localization of ORAI1 and may participate in the regulation of Ca(2+) signaling and the VWF release in response to inflammatory stimuli.
• Tissue Specificity: Highly expressed in primary endothelial cells . Expressed in the embryo heart . Weakly expressed the embryo skeletal muscle .

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[1]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[2]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[1]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Obstructive sleep apnea	DIS0SVD1	Strong	Genetic Variation	[4]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[5]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[6]

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-18 (TSPAN18).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Tetraspanin-18 (TSPAN18).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tetraspanin-18 (TSPAN18).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tetraspanin-18 (TSPAN18).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tetraspanin-18 (TSPAN18).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tetraspanin-18 (TSPAN18).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tetraspanin-18 (TSPAN18).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tetraspanin-18 (TSPAN18).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tetraspanin-18 (TSPAN18).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tetraspanin-18 (TSPAN18).	[15]

References

• [1] TSPAN1 upregulates MMP2 to promote pancreatic cancer cell migration and invasion via PLC.Oncol Rep. 2019 Apr;41(4):2117-2125. doi: 10.3892/or.2019.6989. Epub 2019 Jan 30.
• [2] Accurate discrimination of Barrett's esophagus and esophageal adenocarcinoma using a quantitative three-tiered algorithm and multimarker real-time reverse transcription-PCR.Clin Cancer Res. 2005 Mar 15;11(6):2205-14. doi: 10.1158/1078-0432.CCR-04-1091.
• [3] Overexpression of TSPAN8 Promotes Tumor Cell Viability and Proliferation in Nonsmall Cell Lung Cancer.Cancer Biother Radiopharm. 2016 Dec;31(10):353-359. doi: 10.1089/cbr.2016.2108.
• [4] Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.Am J Respir Crit Care Med. 2016 Oct 1;194(7):886-897. doi: 10.1164/rccm.201512-2431OC.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Study of the tetraspanin 18 association with schizophrenia in a Han Chinese population.Psychiatry Res. 2016 Jul 30;241:263-6. doi: 10.1016/j.psychres.2016.03.057. Epub 2016 May 11.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] 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.
• [11] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] 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.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.