Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXA5C6L)

• DOT Name: Oligodendrocyte-myelin glycoprotein (OMG)
• Gene Name: OMG
• Related Disease:
  Autism
  Brain neoplasm
  GLUT1 deficiency syndrome
  Malignant peripheral nerve sheath tumor
  Neoplasm
  Neurofibromatosis type 1
  Obesity
  Plexiform neurofibroma
  Ptosis
  Primary progressive multiple sclerosis
  Stroke
  Non-insulin dependent diabetes
  Intellectual disability
• UniProt ID: OMGP_HUMAN
• Pfam ID: PF00560 ; PF13855 ; PF01462
• Sequence:
  MEYQILKMSLCLFILLFLTPGILCICPLQCICTERHRHVDCSGRNLSTLPSGLQENIIHL
  NLSYNHFTDLHNQLTQYTNLRTLDISNNRLESLPAHLPRSLWNMSAANNNIKLLDKSDTA
  YQWNLKYLDVSKNMLEKVVLIKNTLRSLEVLNLSSNKLWTVPTNMPSKLHIVDLSNNSLT
  QILPGTLINLTNLTHLYLHNNKFTFIPDQSFDQLFQLQEITLYNNRWSCDHKQNITYLLK
  WMMETKAHVIGTPCSTQISSLKEHNMYPTPSGFTSSLFTVSGMQTVDTINSLSVVTQPKV
  TKIPKQYRTKETTFGATLSKDTTFTSTDKAFVPYPEDTSTETINSHEAAAATLTIHLQDG
  MVTNTSLTSSTKSSPTPMTLSITSGMPNNFSEMPQQSTTLNLWREETTTNVKTPLPSVAN
  AWKVNASFLLLLNVVVMLAV
• Function: Cell adhesion molecule contributing to the interactive process required for myelination in the central nervous system.
• Tissue Specificity: Oligodendrocytes and myelin of the central nervous system.
• Reactome Pathway: Axonal growth inhibition (RHOA activation) (R-HSA-193634)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Genetic Variation	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]
GLUT1 deficiency syndrome	DIS8OXEB	Strong	Genetic Variation	[3]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Neurofibromatosis type 1	DIS53JH9	Strong	Genetic Variation	[5]
Obesity	DIS47Y1K	Strong	Biomarker	[6]
Plexiform neurofibroma	DISW4XX7	Strong	Biomarker	[4]
Ptosis	DISJZNIY	Strong	Genetic Variation	[7]
Primary progressive multiple sclerosis	DISSHDA5	moderate	Genetic Variation	[5]
Stroke	DISX6UHX	moderate	Biomarker	[8]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[9]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Oligodendrocyte-myelin glycoprotein (OMG).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oligodendrocyte-myelin glycoprotein (OMG).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Oligodendrocyte-myelin glycoprotein (OMG).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Oligodendrocyte-myelin glycoprotein (OMG).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Oligodendrocyte-myelin glycoprotein (OMG).	[14]
Malathion	DMXZ84M	Approved	Malathion affects the expression of Oligodendrocyte-myelin glycoprotein (OMG).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Oligodendrocyte-myelin glycoprotein (OMG).	[16]

References

• [1] Molecular analysis of the oligodendrocyte myelin glycoprotein gene in autistic disorder.Neurosci Lett. 2003 Feb 27;338(2):115-8. doi: 10.1016/s0304-3940(02)01338-1.
• [2] CEST MRI of 3-O-methyl-D-glucose uptake and accumulation in brain tumors.Magn Reson Med. 2019 Mar;81(3):1993-2000. doi: 10.1002/mrm.27489. Epub 2018 Sep 11.
• [3] T295M-associated Glut1 deficiency syndrome with normal erythrocyte 3-OMG uptake.Brain Dev. 2011 Apr;33(4):316-20. doi: 10.1016/j.braindev.2010.06.012. Epub 2010 Jul 13.
• [4] Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients.Mol Med. 2011 Jan-Feb;17(1-2):79-87. doi: 10.2119/molmed.2010.00079. Epub 2010 Sep 10.
• [5] Detailed analysis of the oligodendrocyte myelin glycoprotein gene in four patients with neurofibromatosis 1 and primary progressive multiple sclerosis.J Neurol Neurosurg Psychiatry. 2000 May;68(5):643-6. doi: 10.1136/jnnp.68.5.643.
• [6] Upregulation of intestinal glucose transporters after Roux-en-Y gastric bypass to prevent carbohydrate malabsorption.Obesity (Silver Spring). 2014 Oct;22(10):2164-71. doi: 10.1002/oby.20829. Epub 2014 Jul 2.
• [7] Sensitivity and specificity of single-fibre EMG in the diagnosis of ocular myasthenia varies accordingly to clinical presentation.J Neurol. 2020 Mar;267(3):739-745. doi: 10.1007/s00415-019-09631-3. Epub 2019 Nov 16.
• [8] Growth-associated gene and protein expression in the region of axonal sprouting in the aged brain after stroke.Neurobiol Dis. 2006 Aug;23(2):362-73. doi: 10.1016/j.nbd.2006.03.011. Epub 2006 Jun 19.
• [9] Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes.Diabetes Obes Metab. 2017 Feb;19(2):290-293. doi: 10.1111/dom.12812. Epub 2016 Nov 21.
• [10] Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation.Neurogenetics. 2006 Mar;7(1):59-66. doi: 10.1007/s10048-005-0026-9. Epub 2006 Jan 20.
• [11] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [12] Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
• [13] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [14] 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.
• [15] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [16] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.