Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYHX5MI)

• DOT Name: Peroxisomal membrane protein 2 (PXMP2)
• Synonyms: 22 kDa peroxisomal membrane protein
• Gene Name: PXMP2
• Related Disease:
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease type 1
  Charcot-Marie-Tooth disease type 1A
  Hereditary neuropathy with liability to pressure palsies
  Charcot-Marie-Tooth disease type 3
  Chronic inflammatory demyelinating polyneuropathy
  Demyelinating polyneuropathy
• UniProt ID: PXMP2_HUMAN
• Pfam ID: PF04117
• Sequence:
  MAPAASRLRAEAGLGALPRRALAQYLLFLRLYPVLTKAATSGILSALGNFLAQMIEKKRK
  KENSRSLDVGGPLRYAVYGFFFTGPLSHFFYFFMEHWIPPEVPLAGLRRLLLDRLVFAPA
  FLMLFFLIMNFLEGKDASAFAAKMRGGFWPALRMNWRVWTPLQFININYVPLKFRVLFAN
  LAALFWYAYLASLGK
• Function: Seems to be involved in pore-forming activity and may contribute to the unspecific permeability of the peroxisomal membrane.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway:
  Class I peroxisomal membrane protein import (R-HSA-9603798)
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[1]
Charcot-Marie-Tooth disease type 1	DIS56F9A	Strong	Genetic Variation	[2]
Charcot-Marie-Tooth disease type 1A	DISSRZG7	Strong	Biomarker	[3]
Hereditary neuropathy with liability to pressure palsies	DISY0X1V	Strong	Genetic Variation	[4]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	moderate	Genetic Variation	[5]
Chronic inflammatory demyelinating polyneuropathy	DISNGBLD	moderate	Genetic Variation	[5]
Demyelinating polyneuropathy	DIS7IO4W	Limited	Genetic Variation	[6]

13 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 Peroxisomal membrane protein 2 (PXMP2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peroxisomal membrane protein 2 (PXMP2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Peroxisomal membrane protein 2 (PXMP2).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peroxisomal membrane protein 2 (PXMP2).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Peroxisomal membrane protein 2 (PXMP2).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Peroxisomal membrane protein 2 (PXMP2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Peroxisomal membrane protein 2 (PXMP2).	[19]

References

• [1] Cochlear implantation in a patient with deafness induced by Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathies).J Laryngol Otol. 2006 Jun;120(6):508-10. doi: 10.1017/S0022215106000727.
• [2] Spinal deformities in hereditary motor and sensory neuropathy: a retrospective qualitative, quantitative, genotypical, and familial analysis of 175 patients.Spine (Phila Pa 1976). 2007 Oct 15;32(22):2502-8. doi: 10.1097/BRS.0b013e3181573d4e.
• [3] A novel point mutation in the peripheral myelin protein 22 (PMP22) gene associated with Charcot-Marie-Tooth disease type 1A.Neurology. 1997 Feb;48(2):489-93. doi: 10.1212/wnl.48.2.489.
• [4] CNS myelination and PLP gene dosage.Pharmacogenomics. 2001 Aug;2(3):263-72. doi: 10.1517/14622416.2.3.263.
• [5] PMP-22 gene duplications and deletions identified in archival, paraffin-embedded sural nerve biopsy specimens: correlation to structural changes.Acta Neuropathol. 1998 Jul;96(1):13-21. doi: 10.1007/s004010050855.
• [6] Advances in the genetics of hereditary hypertrophic neuropathy in childhood.Brain Dev. 1995;17 Suppl:31-8.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] 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.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] 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.
• [15] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [18] 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.
• [19] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.