Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLYX1ZZ)

• DOT Name: Transmembrane emp24 domain-containing protein 6 (TMED6)
• Synonyms: p24 family protein gamma-5; p24gamma5
• Gene Name: TMED6
• Related Disease:
  Alveolar soft part sarcoma
  Colorectal carcinoma
  Esophageal cancer
  Gastric cancer
  Hepatocellular carcinoma
  Lung cancer
• UniProt ID: TMED6_HUMAN
• Pfam ID: PF01105
• Sequence:
  MSPLLFGAGLVVLNLVTSARSQKTEPLSGSGDQPLFRGADRYDFAIMIPPGGTECFWQFA
  HQTGYFYFSYEVQRTVGMSHDRHVAATAHNPQGFLIDTSQGVRGQINFSTQETGFYQLCL
  SNQHNHFGSVQVYLNFGVFYEGPETDHKQKERKQLNDTLDAIEDGTQKVQNNIFHMWRYY
  NFARMRKMADFFLIQSNYNYVNWWSTAQSLVIILSGILQLYFLKRLFNVPTTTDTKKPRC

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alveolar soft part sarcoma	DISLKJKZ	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[1]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]

9 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 emp24 domain-containing protein 6 (TMED6).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transmembrane emp24 domain-containing protein 6 (TMED6).	[9]

References

• [1] TMED6-COG8 is a novel molecular marker of TFE3 translocation renal cell carcinoma.Int J Clin Exp Pathol. 2015 Mar 1;8(3):2690-9. eCollection 2015.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.