Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEGF2BV)

• DOT Name: Transmembrane protein 176B (TMEM176B)
• Synonyms: Protein LR8
• Gene Name: TMEM176B
• Related Disease:
  Alzheimer disease
  Amyloidosis
  Carcinoma of liver and intrahepatic biliary tract
  Clear cell renal carcinoma
  Liver cancer
  Neoplasm
  Renal cell carcinoma
• UniProt ID: T176B_HUMAN
• Pfam ID: PF04103
• Sequence:
  MTQNTVIVNGVAMASRPSQPTHVNVHIHQESALTQLLKAGGSLKKFLFHPGDTVPSTARI
  GYEQLALGVTQILLGVVSCVLGVCLSLGPWTVLSASGCAFWAGSVVIAAGAGAIVHEKHP
  GKLAGYISSLLTLAGFATAMAAVVLCVNSFIWQTEPFLYIDTVCDRSDPVFPTTGYRWMR
  RSQENQWQKEECRAYMQMLRKLFTAIRALFLAVCVLKVIVSLVSLGVGLRNLCGQSSQPL
  NEEGSEKRLLGENSVPPSPSREQTSTAIVL
• Function: May play a role in the process of maturation of dendritic cells. Required for the development of cerebellar granule cells.
• Tissue Specificity: Expressed in lung and dermal fibroblasts.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Amyloidosis	DISHTAI2	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[3]

2 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 protein 176B (TMEM176B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 176B (TMEM176B).	[12]

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 protein 176B (TMEM176B).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 176B (TMEM176B).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transmembrane protein 176B (TMEM176B).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transmembrane protein 176B (TMEM176B).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transmembrane protein 176B (TMEM176B).	[10]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Transmembrane protein 176B (TMEM176B).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 176B (TMEM176B).	[13]

References

• [1] Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease.ASN Neuro. 2010 Jul 12;2(3):e00037. doi: 10.1042/AN20100010.
• [2] Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology.Acta Histochem. 2012 Nov;114(7):705-12. doi: 10.1016/j.acthis.2011.12.006. Epub 2012 Jan 12.
• [3] Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.Cancer Sci. 2014 May;105(5):560-7. doi: 10.1111/cas.12394. Epub 2014 Apr 19.
• [4] Targeting TMEM176B Enhances Antitumor Immunity and Augments the Efficacy of Immune Checkpoint Blockers by Unleashing Inflammasome Activation.Cancer Cell. 2019 May 13;35(5):767-781.e6. doi: 10.1016/j.ccell.2019.04.003.
• [5] 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.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [12] 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.
• [13] 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.