Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIJ0T5J)

• DOT Name: MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2)
• Synonyms: MAM domain-containing protein 1
• Gene Name: MDGA2
• Related Disease:
  Childhood epilepsy with centrotemporal spikes
  Neurotic disorder
  Narcolepsy
  Parkinson disease
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Advanced cancer
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: MDGA2_HUMAN
• Pfam ID: PF07679 ; PF13927 ; PF00629
• Sequence:
  MDLLYGLVWLLTVLLEGISGQGVYAPPTVRIVHSGLACNIEEERYSERVYTIREGETLEL
  TCLVTGHPRPQIRWTKTAGSASDRFQDSSVFNETLRITNIQRHQGGRYYCKAENGLGSPA
  IKSIRVDVYYLDDPVVTVHQSIGEAKEQFYYERTVFLRCVANSNPPVRYSWRRGQEVLLQ
  GSDKGVEIYEPFFTQGETKILKLKNLRPQDYANYSCIASVRNVCNIPDKMVSFRLSNKTA
  SPSIKLLVDDPIVVNPGEAITLVCVTTGGEPAPSLTWVRSFGTLPEKTVLNGGTLTIPAI
  TSDDAGTYSCIANNNVGNPAKKSTNIIVRALKKGRFWITPDPYHKDDNIQIGREVKISCQ
  VEAVPSEELTFSWFKNGRPLRSSERMVITQTDPDVSPGTTNLDIIDLKFTDFGTYTCVAS
  LKGGGISDISIDVNISSSTVPPNLTVPQEKSPLVTREGDTIELQCQVTGKPKPIILWSRA
  DKEVAMPDGSMQMESYDGTLRIVNVSREMSGMYRCQTSQYNGFNVKPREALVQLIVQYPP
  AVEPAFLEIRQGQDRSVTMSCRVLRAYPIRVLTYEWRLGNKLLRTGQFDSQEYTEYAVKS
  LSNENYGVYNCSIINEAGAGRCSFLVTGKAYAPEFYYDTYNPVWQNRHRVYSYSLQWTQM
  NPDAVDRIVAYRLGIRQAGQQRWWEQEIKINGNIQKGELITYNLTELIKPEAYEVRLTPL
  TKFGEGDSTIRVIKYSAPVNPHLREFHCGFEDGNICLFTQDDTDNFDWTKQSTATRNTKY
  TPNTGPNADRSGSKEGFYMYIETSRPRLEGEKARLLSPVFSIAPKNPYGPTNTAYCFSFF
  YHMYGQHIGVLNVYLRLKGQTTIENPLWSSSGNKGQRWNEAHVNIYPITSFQLIFEGIRG
  PGIEGDIAIDDVSIAEGECAKQDLATKNSVDGAVGILVHIWLFPIIVLISILSPRR
• Function: May be involved in cell-cell interactions.
• Tissue Specificity: Detected in Leydig cells, syncytiotrophoblast, duodenal villi epithelial cells and neutrophils from kidney and cutaneous squamous cell carcinoma (at protein level).
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Definitive	Biomarker	[1]
Neurotic disorder	DIS1YCE9	Definitive	Genetic Variation	[2]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[3]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Gastric cancer	DISXGOUK	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]
Stomach cancer	DISKIJSX	Limited	Biomarker	[7]

4 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 MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2).	[10]

References

• [1] Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism.Epilepsia. 2012 Sep;53(9):1526-38. doi: 10.1111/j.1528-1167.2012.03559.x. Epub 2012 Jun 27.
• [2] Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism.Arch Gen Psychiatry. 2008 Sep;65(9):1062-71. doi: 10.1001/archpsyc.65.9.1062.
• [3] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [4] A Pooling Genome-Wide Association Study Combining a Pathway Analysis for Typical Sporadic Parkinson's Disease in the Han Population of Chinese Mainland.Mol Neurobiol. 2016 Sep;53(7):4302-18. doi: 10.1007/s12035-015-9331-y. Epub 2015 Jul 31.
• [5] Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
• [6] Single-nucleotide polymorphisms of MAMDC1 are associated with rash and photosensitivity, but not disease risk, of systemic lupus erythematosus in Chinese mainland population.Clin Rheumatol. 2011 Oct;30(10):1373-8. doi: 10.1007/s10067-011-1794-2. Epub 2011 Jun 10.
• [7] MDGA2 is a novel tumour suppressor cooperating with DMAP1 in gastric cancer and is associated with disease outcome.Gut. 2016 Oct;65(10):1619-31. doi: 10.1136/gutjnl-2015-309276. Epub 2015 Jul 23.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.