Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT63ZT3X)

• DOT Name: Transmembrane protein 135 (TMEM135)
• Synonyms: Peroxisomal membrane protein 52; PMP52
• Gene Name: TMEM135
• Related Disease:
  Neoplasm
  Intellectual disability
  Osteoporosis
  Prostate cancer
  Prostate carcinoma
  Glioblastoma multiforme
  Non-small-cell lung cancer
• UniProt ID: TM135_HUMAN
• Pfam ID: PF02466 ; PF15982
• Sequence:
  MAALSKSIPHNCYEIGHTWHPSCRVSFLQITGGALEESLKIYAPLYLIAAILRKRKLDYY
  LHKLLPEILQSASFLTANGALYMAFFCILRKILGKFYSWTPGFGAALPASYVAILIERKS
  RRGLLTIYMANLATETLFRMGVARGTITTLRNGEVLLFCITAAMYMFFFRCKDGLKGFTF
  SALRFIVGKEEIPTHSFSPEAAYAKVEQKREQHEEKPGRMNMIGLVRKFVDSICKHGPRH
  RCCKHYEDNCISYCIKGFIRMFSVGYLIQCCLRIPSAFRHLFTQPSRLLSLFYNKENFQL
  GAFLGSFVSIYKGTSCFLRWIRNLDDELHAIIAGFLAGISMMFYKSTTISMYLASKLVET
  MYFKGIEAGKVPYFPHADTIIYSISTAICFQAAVMEVQTLRPSYWKFLLRLTKGKFAVMN
  RKVLDVFGTGASKHFQDFIPRLDPRYTTVTPELPTEFS
• Function: Involved in mitochondrial metabolism by regulating the balance between mitochondrial fusion and fission. May act as a regulator of mitochondrial fission that promotes DNM1L-dependent fission through activation of DNM1L. May be involved in peroxisome organization.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[2]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Transmembrane protein 135 (TMEM135) affects the response to substance of Paclitaxel.	[20]

13 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 135 (TMEM135).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 135 (TMEM135).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 135 (TMEM135).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 135 (TMEM135).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 135 (TMEM135).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 135 (TMEM135).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 135 (TMEM135).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane protein 135 (TMEM135).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protein 135 (TMEM135).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transmembrane protein 135 (TMEM135).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 135 (TMEM135).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 135 (TMEM135).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transmembrane protein 135 (TMEM135).	[19]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane protein 135 (TMEM135).	[12]

References

• [1] Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study.Breast Cancer Res. 2011;13(6):R114. doi: 10.1186/bcr3057. Epub 2011 Nov 17.
• [2] Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.
• [3] Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.Hum Mol Genet. 2014 Jun 1;23(11):3054-68. doi: 10.1093/hmg/ddt675. Epub 2014 Jan 14.
• [4] Targeting genomic rearrangements in tumor cells through Cas9-mediated insertion of a suicide gene.Nat Biotechnol. 2017 Jun;35(6):543-550. doi: 10.1038/nbt.3843. Epub 2017 May 1.
• [5] Identification of recurrent fusion genes across multiple cancer types.Sci Rep. 2019 Jan 31;9(1):1074. doi: 10.1038/s41598-019-38550-6.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] 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.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] 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.
• [14] 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.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] 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.