Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8Q1582)

• DOT Name: Neuronal membrane glycoprotein M6-b (GPM6B)
• Synonyms: M6b
• Gene Name: GPM6B
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Leukodystrophy
  Nervous system disease
  Pelizeaus-Merzbacher spectrum disorder
  Advanced cancer
  Neoplasm
  Breast cancer
  Breast carcinoma
  Rett syndrome
• UniProt ID: GPM6B_HUMAN
• Pfam ID: PF01275
• Sequence:
  MKPAMETAAEENTEQSQERKGCFECCIKCLGGVPYASLVATILCFSGVALFCGCGHVALA
  GTVAILEQHFSTNASDHALLSEVIQLMQYVIYGIASFFFLYGIILLAEGFYTTSAVKELH
  GEFKTTACGRCISGMFVFLTYVLGVAWLGVFGFSAVPVFMFYNIWSTCEVIKSPQTNGTT
  GVEQICVDIRQYGIIPWNAFPGKICGSALENICNTNEFYMSYHLFIVACAGAGATVIALL
  IYMMATTYNYAVLKFKSREDCCTKF
• Function: May be involved in neural development. Involved in regulation of osteoblast function and bone formation. Involved in matrix vesicle release by osteoblasts; this function seems to involve maintenance of the actin cytoskeleton. May be involved in cellular trafficking of SERT and thereby in regulation of serotonin uptake.
• Tissue Specificity: Neurons and glia; cerebellar Bergmann glia, in glia within white matter tracts of the cerebellum and cerebrum, and in embryonic dorsal root ganglia.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Leukodystrophy	DISVY1TT	Strong	Genetic Variation	[2]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[3]
Pelizeaus-Merzbacher spectrum disorder	DIS1ODJO	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[5]
Breast cancer	DIS7DPX1	Limited	Biomarker	[6]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[6]
Rett syndrome	DISGG5UV	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Neuronal membrane glycoprotein M6-b (GPM6B) affects the response to substance of Etoposide.	[26]

1 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 Neuronal membrane glycoprotein M6-b (GPM6B).	[8]

21 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 Neuronal membrane glycoprotein M6-b (GPM6B).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[16]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[18]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[19]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[16]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[16]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[20]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Neuronal membrane glycoprotein M6-b (GPM6B).	[25]

References

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• [2] PLP1 and GPM6B intragenic copy number analysis by MAPH in 262 patients with hypomyelinating leukodystrophies: Identification of one partial triplication and two partial deletions of PLP1.Neurogenetics. 2006 Mar;7(1):31-7. doi: 10.1007/s10048-005-0021-1. Epub 2006 Jan 17.
• [3] Chromosomal mapping of the human M6 genes.Genomics. 1996 May 1;33(3):532-6. doi: 10.1006/geno.1996.0231.
• [4] Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes.Cell Oncol (Dordr). 2014 Jun;37(3):179-91. doi: 10.1007/s13402-014-0171-y. Epub 2014 Jun 12.
• [5] Vascular marker expression during the development of various types of gynaecological malignancy.Tumour Biol. 2014 Nov;35(11):11229-35. doi: 10.1007/s13277-014-2447-2. Epub 2014 Aug 12.
• [6] Breast carcinoma progression and tumour vascular markers related to apoptotic mechanisms.Dis Markers. 2014;2014:156034. doi: 10.1155/2014/156034. Epub 2014 Feb 18.
• [7] Mutation analysis of the M6b gene in patients with Rett syndrome.Am J Med Genet. 1998 Jun 30;78(2):165-8. doi: 10.1002/(sici)1096-8628(19980630)78:2<165::aid-ajmg13>3.0.co;2-l.
• [8] 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.
• [9] 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.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [13] 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.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [17] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [18] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [19] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [20] Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
• [21] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [22] 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.
• [23] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [24] 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.
• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [26] 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.