Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKYV2NE)

• DOT Name: Myelin P2 protein (PMP2)
• Synonyms: Peripheral myelin protein 2
• Gene Name: PMP2
• Related Disease:
  Advanced cancer
  Charcot-Marie-Tooth disease type 1
  Charcot-Marie-Tooth disease type 4A
  Charcot-Marie-Tooth disease, demyelinating, type 1G
  Cryptococcal meningitis
  Melanoma
  Peripheral neuropathy
  Schizophrenia
  Charcot marie tooth disease
• UniProt ID: MYP2_HUMAN
• PDB ID: 2WUT; 3NR3; 4A1H; 4A1Y; 4A8Z; 4BVM; 4D6A; 4D6B; 5N4M; 5N4P; 5N4Q; 6EW2; 6EW4; 6EW5; 6S2M; 6S2S; 6STS; 6XU5; 6XU9; 6XUA; 6XUW; 6XVQ; 6XVR; 6XVS; 6XVY; 6XW9; 7NRW; 7NSR; 7NTP; 7O60
• Pfam ID: PF00061
• Sequence:
  MSNKFLGTWKLVSSENFDDYMKALGVGLATRKLGNLAKPTVIISKKGDIITIRTESTFKN
  TEISFKLGQEFEETTADNRKTKSIVTLQRGSLNQVQRWDGKETTIKRKLVNGKMVAECKM
  KGVVCTRIYEKV
• Function: May play a role in lipid transport protein in Schwann cells. May bind cholesterol.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Charcot-Marie-Tooth disease type 1	DIS56F9A	Strong	Genetic Variation	[2]
Charcot-Marie-Tooth disease type 4A	DIS7XS5C	Strong	Biomarker	[3]
Charcot-Marie-Tooth disease, demyelinating, type 1G	DISL4IGJ	Strong	Autosomal dominant	[4]
Cryptococcal meningitis	DIS1LBC6	Strong	Altered Expression	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[7]
Schizophrenia	DISSRV2N	Strong	Biomarker	[8]
Charcot marie tooth disease	DIS3BT2L	Limited	Autosomal dominant	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Myelin P2 protein (PMP2) affects the response to substance of Etoposide.	[17]

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 Myelin P2 protein (PMP2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Myelin P2 protein (PMP2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of Myelin P2 protein (PMP2).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Myelin P2 protein (PMP2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Myelin P2 protein (PMP2).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Myelin P2 protein (PMP2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Myelin P2 protein (PMP2).	[16]

References

• [1] Genetic identification of intestinal microsporidia species in immunocompromised patients in Tunisia.Am J Trop Med Hyg. 2009 Jan;80(1):24-7.
• [2] De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease.Brain. 2016 Jun;139(Pt 6):1649-56. doi: 10.1093/brain/aww055. Epub 2016 Mar 23.
• [3] Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the defect in CMT4A.Genomics. 1995 Jul 20;28(2):286-90. doi: 10.1006/geno.1995.1143.
• [4] Charcot-Marie-Tooth Neuropathy Type 1 C RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1998 Aug 31 [updated 2015 Mar 26]. 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.
• [5] Characterization of host response to Cryptococcus neoformans through quantitative proteomic analysis of cryptococcal meningitis co-infected with HIV.Mol Biosyst. 2015 Sep;11(9):2529-40. doi: 10.1039/c5mb00187k.
• [6] The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion.Pigment Cell Melanoma Res. 2019 May;32(3):424-434. doi: 10.1111/pcmr.12760. Epub 2018 Dec 21.
• [7] Peripheral myelin protein 2 - a novel cluster of mutations causing Charcot-Marie-Tooth neuropathy.Orphanet J Rare Dis. 2019 Aug 14;14(1):197. doi: 10.1186/s13023-019-1162-x.
• [8] Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients.Neurobiol Dis. 2006 Mar;21(3):531-40. doi: 10.1016/j.nbd.2005.08.012. Epub 2005 Oct 5.
• [9] 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.
• [10] 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.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [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.