Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3IZBM0)

• DOT Name: Transmembrane protein 74 (TMEM74)
• Gene Name: TMEM74
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Hepatocellular carcinoma
  Liver cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Advanced cancer
  Alopecia
• UniProt ID: TMM74_HUMAN
• Pfam ID: PF14927
• Sequence:
  MELHYLAKKSNQADLCDARDWSSRGLPGDQADTAATRAALCCQKQCASTPRATEMEGSKL
  SSSPASPSSSLQNSTLQPDAFPPGLLHSGNNQITAERKVCNCCSQELETSFTYVDKNINL
  EQRNRSSPSAKGHNHPGELGWENPNEWSQEAAISLISEEEDDTSSEATSSGKSIDYGFIS
  AILFLVTGILLVIISYIVPREVTVDPNTVAAREMERLEKESARLGAHLDRCVIAGLCLLT
  LGGVILSCLLMMSMWKGELYRRNRFASSKESAKLYGSFNFRMKTSTNENTLELSLVEEDA
  LAVQS
• Function: Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction.
• Tissue Specificity: Expressed in heart, lung, and placenta.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[1]
Alopecia	DIS37HU4	Limited	Genetic Variation	[3]

11 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 protein 74 (TMEM74).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 74 (TMEM74).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 74 (TMEM74).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transmembrane protein 74 (TMEM74).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Transmembrane protein 74 (TMEM74).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transmembrane protein 74 (TMEM74).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transmembrane protein 74 (TMEM74).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transmembrane protein 74 (TMEM74).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 74 (TMEM74).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane protein 74 (TMEM74).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Transmembrane protein 74 (TMEM74).	[13]

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 protein 74 (TMEM74).	[10]

References

• [1] The Expression of TMEM74 in Liver Cancer and Lung Cancer Correlating With Survival Outcomes.Appl Immunohistochem Mol Morphol. 2019 Sep;27(8):618-625. doi: 10.1097/PAI.0000000000000659.
• [2] TMEM74 promotes tumor cell survival by inducing autophagy via interactions with ATG16L1 and ATG9A.Cell Death Dis. 2017 Aug 31;8(8):e3031. doi: 10.1038/cddis.2017.370.
• [3] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.