Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAR2YXH)

DOT Name Myelin protein P0 (MPZ)
Synonyms Myelin peripheral protein; MPP; Myelin protein zero
Gene Name MPZ
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Charcot marie tooth disease ( )
Charcot-Marie-Tooth disease type 1B ( )
Deafness ( )
Neuropathy, congenital hypomyelinating, 2 ( )
Alzheimer disease ( )
Autoimmune disease ( )
Charcot-Marie-Tooth disease type 1A ( )
Charcot-Marie-Tooth disease type 4E ( )
Chronic inflammatory demyelinating polyneuropathy ( )
Colonic neoplasm ( )
Colorectal adenoma ( )
Colorectal neoplasm ( )
Crohn disease ( )
Demyelinating polyneuropathy ( )
Diabetic neuropathy ( )
Disorder of sexual differentiation ( )
Hereditary neuropathy with liability to pressure palsies ( )
Inflammatory bowel disease ( )
Movement disorder ( )
Neuroblastoma ( )
Parkinson disease ( )
Parkinsonian disorder ( )
PCWH syndrome ( )
Peripheral neuropathy ( )
Sciatic neuropathy ( )
Systemic sclerosis ( )
X-linked adrenal hypoplasia congenita ( )
Charcot-Marie-Tooth disease type 1 ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Neoplasm ( )
Neurodegenerative disease ( )
Peripheral sensory neuropathies ( )
Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain ( )
Charcot-Marie-Tooth disease dominant intermediate D ( )
Charcot-Marie-Tooth disease type 2I ( )
Charcot-Marie-Tooth disease type 2J ( )
Charcot-Marie-Tooth disease type 3 ( )
Polyneuropathy ( )
Charcot-Marie-Tooth disease X-linked dominant 1 ( )
Dengue ( )
Nervous system disease ( )
Neuropathy, congenital hypomelinating ( )
Ulcerative colitis ( )
UniProt ID
MYP0_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3OAI; 8IIA
Pfam ID
PF10570 ; PF07686
Sequence
MAPGAPSSSPSPILAVLLFSSLVLSPAQAIVVYTDREVHGAVGSRVTLHCSFWSSEWVSD
DISFTWRYQPEGGRDAISIFHYAKGQPYIDEVGTFKERIQWVGDPRWKDGSIVIHNLDYS
DNGTFTCDVKNPPDIVGKTSQVTLYVFEKVPTRYGVVLGAVIGGVLGVVLLLLLLFYVVR
YCWLRRQAALQRRLSAMEKGKLHKPGKDASKRGRQTPVLYAMLDHSRSTKAVSEKKAKGL
GESRKDKK
Function Is an adhesion molecule necessary for normal myelination in the peripheral nervous system. It mediates adhesion between adjacent myelin wraps and ultimately drives myelin compaction.
Tissue Specificity Found only in peripheral nervous system Schwann cells.
KEGG Pathway
Cell adhesion molecules (hsa04514 )
Reactome Pathway
EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Definitive Biomarker [1]
Breast carcinoma DIS2UE88 Definitive Biomarker [1]
Charcot marie tooth disease DIS3BT2L Definitive Autosomal dominant [2]
Charcot-Marie-Tooth disease type 1B DISJRS1V Definitive Autosomal dominant [3]
Deafness DISKCLH4 Definitive Biomarker [4]
Neuropathy, congenital hypomyelinating, 2 DISRN8BK Definitive Autosomal dominant [5]
Alzheimer disease DISF8S70 Strong Biomarker [6]
Autoimmune disease DISORMTM Strong Biomarker [7]
Charcot-Marie-Tooth disease type 1A DISSRZG7 Strong Genetic Variation [8]
Charcot-Marie-Tooth disease type 4E DIS5RRJE Strong Biomarker [9]
Chronic inflammatory demyelinating polyneuropathy DISNGBLD Strong Biomarker [10]
Colonic neoplasm DISSZ04P Strong Genetic Variation [11]
Colorectal adenoma DISTSVHM Strong Biomarker [12]
Colorectal neoplasm DISR1UCN Strong Biomarker [13]
Crohn disease DIS2C5Q8 Strong Biomarker [14]
Demyelinating polyneuropathy DIS7IO4W Strong Genetic Variation [15]
Diabetic neuropathy DISX6VF8 Strong Therapeutic [16]
Disorder of sexual differentiation DISRMAEZ Strong Genetic Variation [17]
Hereditary neuropathy with liability to pressure palsies DISY0X1V Strong Biomarker [18]
Inflammatory bowel disease DISGN23E Strong Altered Expression [19]
Movement disorder DISOJJ2D Strong Genetic Variation [9]
Neuroblastoma DISVZBI4 Strong Biomarker [20]
Parkinson disease DISQVHKL Strong Biomarker [21]
Parkinsonian disorder DISHGY45 Strong Genetic Variation [22]
PCWH syndrome DISLOQND Strong Biomarker [23]
Peripheral neuropathy DIS7KN5G Strong Genetic Variation [24]
Sciatic neuropathy DISMGDKX Strong Therapeutic [25]
Systemic sclerosis DISF44L6 Strong Biomarker [26]
X-linked adrenal hypoplasia congenita DISNMXY8 Strong Biomarker [27]
Charcot-Marie-Tooth disease type 1 DIS56F9A moderate Biomarker [28]
Colon cancer DISVC52G moderate Biomarker [29]
Colon carcinoma DISJYKUO moderate Biomarker [29]
Colorectal carcinoma DIS5PYL0 moderate Biomarker [30]
Neoplasm DISZKGEW moderate Biomarker [31]
Neurodegenerative disease DISM20FF moderate Biomarker [32]
Peripheral sensory neuropathies DISYWI6M moderate Genetic Variation [33]
Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain DISHGY84 Supportive Autosomal dominant [34]
Charcot-Marie-Tooth disease dominant intermediate D DISYWZTH Supportive Autosomal dominant [35]
Charcot-Marie-Tooth disease type 2I DISOJA8B Supportive Autosomal dominant [36]
Charcot-Marie-Tooth disease type 2J DISZ5R0M Supportive Autosomal dominant [36]
Charcot-Marie-Tooth disease type 3 DIS6DQK1 Supportive Autosomal dominant [37]
Polyneuropathy DISB9G3W Disputed Genetic Variation [38]
Charcot-Marie-Tooth disease X-linked dominant 1 DISC6S1R Limited Genetic Variation [17]
Dengue DISKH221 Limited Biomarker [39]
Nervous system disease DISJ7GGT Limited Altered Expression [40]
Neuropathy, congenital hypomelinating DISZUW4L Limited Genetic Variation [41]
Ulcerative colitis DIS8K27O Limited Altered Expression [42]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Myelin protein P0 (MPZ). [43]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Myelin protein P0 (MPZ). [44]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Myelin protein P0 (MPZ). [45]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Myelin protein P0 (MPZ). [46]
Quercetin DM3NC4M Approved Quercetin increases the expression of Myelin protein P0 (MPZ). [47]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Myelin protein P0 (MPZ). [48]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Myelin protein P0 (MPZ). [49]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Myelin protein P0 (MPZ). [43]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Myelin protein P0 (MPZ). [50]
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⏷ Show the Full List of 9 Drug(s)

References

1 Estrogen Receptor Status Oppositely Modifies Breast Cancer Prognosis in BRCA1/BRCA2 Mutation Carriers Versus Non-Carriers.Cancers (Basel). 2019 May 28;11(6):738. doi: 10.3390/cancers11060738.
2 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
4 Human cytomegalovirus (HCMV) and hearing impairment: infection of fibroblast cells with HCMV induces chromosome breaks at 1q23.3, between loci DFNA7 and DFNA49 -- both involved in dominantly inherited, sensorineural, hearing impairment.Mutat Res. 2008 Jan 1;637(1-2):56-65. doi: 10.1016/j.mrfmmm.2007.07.009. Epub 2007 Jul 25.
5 A novel MPZ gene mutation in congenital neuropathy with hypomyelination. Neurology. 2004 Jun 8;62(11):2122-3. doi: 10.1212/01.wnl.0000127606.93772.3a.
6 Wechsler adult intelligence scale-4th edition digit span performance in subjective cognitive complaints, amnestic mild cognitive impairment, and probable dementia of the Alzheimer type.Clin Neuropsychol. 2019 Nov;33(8):1436-1444. doi: 10.1080/13854046.2019.1585574. Epub 2019 Mar 31.
7 CARD9 mediates dendritic cell-induced development of Lyn deficiency-associated autoimmune and inflammatory diseases.Sci Signal. 2019 Oct 8;12(602):eaao3829. doi: 10.1126/scisignal.aao3829.
8 New polymorphic short tandem repeats for PCR-based Charcot-Marie-Tooth disease type 1A duplication diagnosis.Clin Chem. 2001 May;47(5):838-43.
9 Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.Brain. 2015 Nov;138(Pt 11):3180-92. doi: 10.1093/brain/awv241. Epub 2015 Aug 25.
10 Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes.Front Neurol. 2018 Mar 19;9:171. doi: 10.3389/fneur.2018.00171. eCollection 2018.
11 Differential expression of LEF1/TCFs family members in colonic carcinogenesis.Mol Carcinog. 2017 Nov;56(11):2372-2381. doi: 10.1002/mc.22530. Epub 2017 May 22.
12 Glucocorticoids promote the development of azoxymethane and dextran sulfate sodium-induced colorectal carcinoma in mice.BMC Cancer. 2019 Jan 21;19(1):94. doi: 10.1186/s12885-019-5299-8.
13 PPAR agonist enhances colitis-associated colorectal cancer.Eur J Pharmacol. 2019 Jan 5;842:248-254. doi: 10.1016/j.ejphar.2018.10.050. Epub 2018 Nov 2.
14 Evaluation of anti-inflammatory effect of silver-coated glass beads in mice with experimentally induced colitis as a new type of treatment in inflammatory bowel disease.Pharmacol Rep. 2017 Jun;69(3):386-392. doi: 10.1016/j.pharep.2017.01.003. Epub 2017 Jan 12.
15 In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane.Cell Biol Int. 2020 Feb;44(2):671-683. doi: 10.1002/cbin.11268. Epub 2019 Dec 4.
16 Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation.J Lipid Res. 2012 Feb;53(2):300-10. doi: 10.1194/jlr.M021188. Epub 2011 Dec 7.
17 Molecular basis of hereditary neuropathies.Phys Med Rehabil Clin N Am. 2001 May;12(2):277-91.
18 Clinical and genetic spectra in a series of Chinese patients with Charcot-Marie-Tooth disease.Clin Chim Acta. 2015 Dec 7;451(Pt B):263-70. doi: 10.1016/j.cca.2015.10.007. Epub 2015 Oct 8.
19 Faecal neutrophil elastase-antiprotease balance reflects colitis severity.Mucosal Immunol. 2020 Mar;13(2):322-333. doi: 10.1038/s41385-019-0235-4. Epub 2019 Nov 26.
20 The long noncoding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression.Oncotarget. 2017 Apr 11;8(15):24449-24456. doi: 10.18632/oncotarget.15511.
21 SH-SY5Y and LUHMES cells display differential sensitivity to MPP+, tunicamycin, and epoxomicin in 2D and 3D cell culture.Biotechnol Prog. 2020 Mar;36(2):e2942. doi: 10.1002/btpr.2942. Epub 2019 Dec 12.
22 Oxidants induce alternative splicing of alpha-synuclein: Implications for Parkinson's disease. Free Radic Biol Med. 2010 Feb 1;48(3):377-83. doi: 10.1016/j.freeradbiomed.2009.10.045. Epub 2009 Oct 23.
23 Heterozygous null mutation of myelin P0 protein enhances susceptibility to autoimmune neuritis targeting P0 peptide.Eur J Immunol. 2003 Mar;33(3):656-65. doi: 10.1002/eji.200323677.
24 A charcot-marie-tooth type 1B kindred associated with hemifacial spasm and trigeminal neuralgia.Muscle Nerve. 2019 Jul;60(1):62-66. doi: 10.1002/mus.26478. Epub 2019 Apr 8.
25 Electrical stimulation enhances peripheral nerve regeneration after crush injury in rats.Mol Med Rep. 2013 May;7(5):1523-7. doi: 10.3892/mmr.2013.1395. Epub 2013 Mar 26.
26 Comparison of dextran-based sirolimus-eluting stents and PLA-based sirolimus-eluting stents in vitro and in vivo.J Biomed Mater Res A. 2017 Jan;105(1):301-310. doi: 10.1002/jbm.a.35898. Epub 2016 Oct 31.
27 Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.J Clin Endocrinol Metab. 1997 Nov;82(11):3835-41. doi: 10.1210/jcem.82.11.4342.
28 A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function.Hum Mol Genet. 2019 Jan 1;28(1):124-132. doi: 10.1093/hmg/ddy336.
29 Construing the Biochemical and Molecular Mechanism Underlying the In Vivo and In Vitro Chemotherapeutic Efficacy of Ruthenium-Baicalein Complex in Colon Cancer.Int J Biol Sci. 2019 Apr 22;15(5):1052-1071. doi: 10.7150/ijbs.31143. eCollection 2019.
30 Metabolic targeting of HIF-1 potentiates the therapeutic efficacy of oxaliplatin in colorectal cancer.Oncogene. 2020 Jan;39(2):414-427. doi: 10.1038/s41388-019-0999-8. Epub 2019 Sep 2.
31 PAR2 deficiency enhances myeloid cell-mediated immunosuppression and promotes colitis-associated tumorigenesis.Cancer Lett. 2020 Jan 28;469:437-446. doi: 10.1016/j.canlet.2019.11.015. Epub 2019 Nov 14.
32 Heterozygous P0 deficiency protects mice from vincristine-induced polyneuropathy.J Neurosci Res. 2006 Jul;84(1):37-46. doi: 10.1002/jnr.20873.
33 A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths.Neurology. 1999 Apr 12;52(6):1271-5. doi: 10.1212/wnl.52.6.1271.
34 Intermediate Charcot-Marie-Tooth disease due to a novel Trp101Stop myelin protein zero mutation associated with debilitating neuropathic pain. Pain. 2012 Aug;153(8):1763-1768. doi: 10.1016/j.pain.2012.05.015. Epub 2012 Jun 16.
35 Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):174-9. doi: 10.1136/jnnp.67.2.174.
36 Charcot-Marie-Tooth Neuropathy Type 2 C RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1998 Sep 24 [updated 2016 Apr 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
37 Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. Neuron. 1996 Sep;17(3):451-60. doi: 10.1016/s0896-6273(00)80177-4.
38 Four novel mutations of the myelin protein zero gene presenting as a mild and late-onset polyneuropathy.J Neurol. 2010 Nov;257(11):1864-8. doi: 10.1007/s00415-010-5624-2. Epub 2010 Jun 18.
39 Development of a live attenuated dengue virus vaccine using reverse genetics.Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
40 A Redox Modulatory Mn(3) O(4) Nanozyme with Multi-Enzyme Activity Provides Efficient Cytoprotection to Human Cells in a Parkinson's Disease Model.Angew Chem Int Ed Engl. 2017 Nov 6;56(45):14267-14271. doi: 10.1002/anie.201708573. Epub 2017 Oct 4.
41 Homozygous splice-site mutation c.78 +?G>A in PMP22 causes congenital hypomyelinating neuropathy.Neuropathology. 2019 Dec;39(6):441-446. doi: 10.1111/neup.12604. Epub 2019 Nov 27.
42 Suppression of miR-21 and miR-155 of macrophage by cinnamaldehyde ameliorates ulcerative colitis.Int Immunopharmacol. 2019 Feb;67:22-34. doi: 10.1016/j.intimp.2018.11.045. Epub 2018 Dec 6.
43 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.
44 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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46 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.
47 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.
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49 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.
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