Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMEU45R)

• DOT Name: Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3)
• Synonyms: tRNA-specific adenosine-34 deaminase subunit ADAT3
• Gene Name: ADAT3
• Related Disease:
  Intellectual disability
  Intellectual disability-strabismus syndrome
• UniProt ID: ADAT3_HUMAN
• Pfam ID: PF00383
• Sequence:
  MEPAPGLVEQPKCLEAGSPEPEPAPWQALPVLSEKQSGDVELVLAYAAPVLDKRQTSRLL
  KEVSALHPLPAQPHLKRVRPSRDAGSPHALEMLLCLAGPASGPRSLAELLPRPAVDPRGL
  GQPFLVPVPARPPLTRGQFEEARAHWPTSFHEDKQVTSALAGRLFSTQERAAMQSHMERA
  VWAARRAAARGLRAVGAVVVDPASDRVLATGHDCSCADNPLLHAVMVCVDLVARGQGRGT
  YDFRPFPACSFAPAAAPQAVRAGAVRKLDADEDGLPYLCTGYDLYVTREPCAMCAMALVH
  ARILRVFYGAPSPDGALGTRFRIHARPDLNHRFQVFRGVLEEQCRWLDPDT
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Intellectual disability-strabismus syndrome	DIS4KGBW	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable inactive tRNA-specific adenosine deaminase-like protein 3 (ADAT3).	[9]

References

• [1] A new case confirming and expanding the phenotype spectrum of ADAT3-related intellectual disability syndrome.Eur J Med Genet. 2019 Nov;62(11):103549. doi: 10.1016/j.ejmg.2018.10.001. Epub 2018 Oct 6.
• [2] Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus. J Med Genet. 2013 Jul;50(7):425-30. doi: 10.1136/jmedgenet-2012-101378. Epub 2013 Apr 25.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.