Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDES2NC)

• DOT Name: Transmembrane 4 L6 family member 18 (TM4SF18)
• Gene Name: TM4SF18
• Related Disease:
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic cancer
• UniProt ID: T4S18_HUMAN
• Pfam ID: PF05805
• Sequence:
  MGSRKCGGCLSCLLIPLALWSIIVNILLYFPNGQTSYASSNKLTNYVWYFEGICFSGIMM
  LIVTTVLLVLENNNNYKCCQSENCSKKYVTLLSIIFSSLGIAFSGYCLVISALGLVQGPY
  CRTLDGWEYAFEGTAGRFLTDSSIWIQCLEPAHVVEWNIILFSILITLSGLQVIICLIRV
  VMQLSKILCGSYSVIFQPGII

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]

8 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 Transmembrane 4 L6 family member 18 (TM4SF18).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[7]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Transmembrane 4 L6 family member 18 (TM4SF18).	[9]

1 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 Transmembrane 4 L6 family member 18 (TM4SF18).	[8]

References

• [1] TM4SF18 is aberrantly expressed in pancreatic cancer and regulates cell growth.PLoS One. 2019 Mar 21;14(3):e0211711. doi: 10.1371/journal.pone.0211711. eCollection 2019.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion. Toxicol In Vitro. 2009 Apr;23(3):486-99.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] 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.
• [7] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [8] 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.
• [9] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.