Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXMU5ZV)

• DOT Name: Transmembrane 6 superfamily member 2 (TM6SF2)
• Gene Name: TM6SF2
• UniProt ID: TM6S2_HUMAN
• Pfam ID: PF05241
• Sequence:
  MDIPPLAGKIAALSLSALPVSYALNHVSALSHPLWVALMSALILGLLFVAVYSLSHGEVS
  YDPLYAVFAVFAFTSVVDLIIALQEDSYVVGFMEFYTKEGEPYLRTAHGVFICYWDGTVH
  YLLYLAMAGAICRRKRYRNFGLYWLGSFAMSILVFLTGNILGKYSSEIRPAFFLTIPYLL
  VPCWAGMKVFSQPRALTRCTANMVQEEQRKGLLQRPADLALVIYLILAGFFTLFRGLVVL
  DCPTDACFVYIYQYEPYLRDPVAYPKVQMLMYMFYVLPFCGLAAYALTFPGCSWLPDWAL
  VFAGGIGQAQFSHMGASMHLRTPFTYRVPEDTWGCFFVCNLLYALGPHLLAYRCLQWPAF
  FHQPPPSDPLALHKKQH
• Function: Regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. May function as sterol isomerase.
• Tissue Specificity: Substantial expression in liver and intestine, whereas all other tissues analyzed show low levels.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Transmembrane 6 superfamily member 2 (TM6SF2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane 6 superfamily member 2 (TM6SF2).	[5]

5 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 6 superfamily member 2 (TM6SF2).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane 6 superfamily member 2 (TM6SF2).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transmembrane 6 superfamily member 2 (TM6SF2).	[3]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Transmembrane 6 superfamily member 2 (TM6SF2).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane 6 superfamily member 2 (TM6SF2).	[6]

References

• [1] 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.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [5] 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.
• [6] 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.