Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane 9 superfamily member 3 (TM9SF3)
• Synonyms: EP70-P-iso; SM-11044-binding protein
• Gene Name: TM9SF3
• Related Disease:
  Neoplasm
  Adult T-cell leukemia/lymphoma
  Gastric cancer
  Stomach cancer
• UniProt ID: TM9S3_HUMAN
• Pfam ID: PF02990
• Sequence:
  MRPLPGALGVAAAAALWLLLLLLPRTRADEHEHTYQDKEEVVLWMNTVGPYHNRQETYKY
  FSLPFCVGSKKSISHYHETLGEALQGVELEFSGLDIKFKDDVMPATYCEIDLDKEKRDAF
  VYAIKNHYWYQMYIDDLPIWGIVGEADENGEDYYLWTYKKLEIGFNGNRIVDVNLTSEGK
  VKLVPNTKIQMSYSVKWKKSDVKFEDRFDKYLDPSFFQHRIHWFSIFNSFMMVIFLVGLV
  SMILMRTLRKDYARYSKEEEMDDMDRDLGDEYGWKQVHGDVFRPSSHPLIFSSLIGSGCQ
  IFAVSLIVIIVAMIEDLYTERGSMLSTAIFVYAATSPVNGYFGGSLYARQGGRRWIKQMF
  IGAFLIPAMVCGTAFFINFIAIYYHASRAIPFGTMVAVCCICFFVILPLNLVGTILGRNL
  SGQPNFPCRVNAVPRPIPEKKWFMEPAVIVCLGGILPFGSIFIEMYFIFTSFWAYKIYYV
  YGFMMLVLVILCIVTVCVTIVCTYFLLNAEDYRWQWTSFLSAASTAIYVYMYSFYYYFFK
  TKMYGLFQTSFYFGYMAVFSTALGIMCGAIGYMGTSAFVRKIYTNVKID

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[3]

1 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 Transmembrane 9 superfamily member 3 (TM9SF3).	[4]

7 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 Transmembrane 9 superfamily member 3 (TM9SF3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane 9 superfamily member 3 (TM9SF3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane 9 superfamily member 3 (TM9SF3).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transmembrane 9 superfamily member 3 (TM9SF3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane 9 superfamily member 3 (TM9SF3).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane 9 superfamily member 3 (TM9SF3).	[8]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Transmembrane 9 superfamily member 3 (TM9SF3).	[10]

References

• [1] Identification of novel transmembrane proteins in scirrhous-type gastric cancer by the Escherichia coli ampicillin secretion trap (CAST) method: TM9SF3 participates in tumor invasion and serves as a prognostic factor.Pathobiology. 2014;81(3):138-48. doi: 10.1159/000357821. Epub 2014 Mar 8.
• [2] miR-1193 Suppresses the Proliferation and Invasion of Human T-Cell Leukemia Cells Through Directly Targeting the Transmembrane 9 Superfamily 3 (TM9SF3).Oncol Res. 2017 Nov 2;25(9):1643-1651. doi: 10.3727/096504017X14908284471361. Epub 2017 Mar 30.
• [3] Clinicopathologic and molecular characteristics of gastric cancer showing gastric and intestinal mucin phenotype.Cancer Sci. 2015 Aug;106(8):951-8. doi: 10.1111/cas.12706. Epub 2015 Jul 7.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [10] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.