Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAJ4CPX)

• DOT Name: Transmembrane protein 47 (TMEM47)
• Synonyms: Brain cell membrane protein 1; Transmembrane 4 superfamily member 10
• Gene Name: TMEM47
• Related Disease:
  X-linked intellectual disability
  Neoplasm
• UniProt ID: TMM47_HUMAN
• Pfam ID: PF00822
• Sequence:
  MASAGSGMEEVRVSVLTPLKLVGLVCIFLALCLDLGAVLSPAWVTADHQYYLSLWESCRK
  PASLDIWHCESTLSSDWQIATLALLLGGAAIILIAFLVGLISICVGSRRRFYRPVAVMLF
  AAVVLQVCSLVLYPIKFIETVSLKIYHEFNWGYGLAWGATIFSFGGAILYCLNPKNYEDY
  Y
• Function: Regulates cell junction organization in epithelial cells. May play a role in the transition from adherens junction to tight junction assembly. May regulate F-actin polymerization required for tight junctional localization dynamics and affect the junctional localization of PARD6B. During podocyte differentiation may negatively regulate activity of FYN and subsequently the abundance of nephrin.
• Tissue Specificity: Expressed in adult brain, fetal brain, cerebellum, heart, lung, prostate and thyroid.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
X-linked intellectual disability	DISYJBY3	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Transmembrane protein 47 (TMEM47) affects the response to substance of Etoposide.	[17]
Mitoxantrone	DMM39BF	Approved	Transmembrane protein 47 (TMEM47) affects the response to substance of Mitoxantrone.	[17]

3 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 protein 47 (TMEM47).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 47 (TMEM47).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transmembrane protein 47 (TMEM47).	[15]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 47 (TMEM47).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 47 (TMEM47).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 47 (TMEM47).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 47 (TMEM47).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 47 (TMEM47).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 47 (TMEM47).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane protein 47 (TMEM47).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Transmembrane protein 47 (TMEM47).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transmembrane protein 47 (TMEM47).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 47 (TMEM47).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane protein 47 (TMEM47).	[16]

References

• [1] TM4SF10 gene sequencing in XLMR patients identifies common polymorphisms but no disease-associated mutation.BMC Med Genet. 2004 Sep 2;5:22. doi: 10.1186/1471-2350-5-22.
• [2] Novel markers of subclinical disease for Ewing family tumors from gene expression profiling.Clin Cancer Res. 2007 Dec 1;13(23):6978-83. doi: 10.1158/1078-0432.CCR-07-1417.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [8] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.
• [15] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [16] 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.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.