Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG6WE4M)

• DOT Name: Protein AAR2 homolog (AAR2)
• Synonyms: AAR2 splicing factor homolog
• Gene Name: AAR2
• Related Disease: Multiple congenital anomalies/dysmorphic syndrome
• UniProt ID: AAR2_HUMAN
• PDB ID: 7PJH
• Pfam ID: PF05282 ; PF20981
• Sequence:
  MAAVQMDPELAKRLFFEGATVVILNMPKGTEFGIDYNSWEVGPKFRGVKMIPPGIHFLHY
  SSVDKANPKEVGPRMGFFLSLHQRGLTVLRWSTLREEVDLSPAPESEVEAMRANLQELDQ
  FLGPYPYATLKKWISLTNFISEATVEKLQPENRQICAFSDVLPVLSMKHTKDRVGQNLPR
  CGIECKSYQEGLARLPEMKPRAGTEIRFSELPTQMFPEGATPAEITKHSMDLSYALETVL
  NKQFPSSPQDVLGELQFAFVCFLLGNVYEAFEHWKRLLNLLCRSEAAMMKHHTLYINLIS
  ILYHQLGEIPADFFVDIVSQDNFLTSTLQVFFSSACSIAVDATLRKKAEKFQAHLTKKFR
  WDFAAEPEDCAPVVVELPEGIEMG
• Function: Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple congenital anomalies/dysmorphic syndrome	DIS0LF2K	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein AAR2 homolog (AAR2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein AAR2 homolog (AAR2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein AAR2 homolog (AAR2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein AAR2 homolog (AAR2).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein AAR2 homolog (AAR2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein AAR2 homolog (AAR2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Protein AAR2 homolog (AAR2).	[5]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.