Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ7XQSI)

• DOT Name: Vang-like protein 2
• Synonyms: Loop-tail protein 1 homolog; Strabismus 1; Van Gogh-like protein 2
• Gene Name: VANGL2
• Related Disease: Neural tube defects, susceptibility to
• UniProt ID: VANG2_HUMAN
• PDB ID: 6XA6; 6XA7; 6XA8; 7R2M; 7R2T
• Pfam ID: PF06638
• Sequence:
  MDTESQYSGYSYKSGHSRSSRKHRDRRDRHRSKSRDGGRGDKSVTIQAPGEPLLDNESTR
  GDERDDNWGETTTVVTGTSEHSISHDDLTRIAKDMEDSVPLDCSRHLGVAAGATLALLSF
  LTPLAFLLLPPLLWREELEPCGTACEGLFISVAFKLLILLLGSWALFFRRPKASLPRVFV
  LRALLMVLVFLLVVSYWLFYGVRILDARERSYQGVVQFAVSLVDALLFVHYLAVVLLELR
  QLQPQFTLKVVRSTDGASRFYNVGHLSIQRVAVWILEKYYHDFPVYNPALLNLPKSVLAK
  KVSGFKVYSLGEENSTNNSTGQSRAVIAAAARRRDNSHNEYYYEEAEHERRVRKRRARLV
  VAVEEAFTHIKRLQEEEQKNPREVMDPREAAQAIFASMARAMQKYLRTTKQQPYHTMESI
  LQHLEFCITHDMTPKAFLERYLAAGPTIQYHKERWLAKQWTLVSEEPVTNGLKDGIVFLL
  KRQDFSLVVSTKKVPFFKLSEEFVDPKSHKFVMRLQSETSV
• Function: Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate. Plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea. Required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process. Required for cell surface localization of FZD3 and FZD6 in the inner ear.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)
• Reactome Pathway:
  Asymmetric localization of PCP proteins (R-HSA-4608870)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  PCP/CE pathway (R-HSA-4086400)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neural tube defects, susceptibility to	DISHA84K	Moderate	Autosomal dominant	[1]

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 Vang-like protein 2.	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Vang-like protein 2.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vang-like protein 2.	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Vang-like protein 2.	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Vang-like protein 2.	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of Vang-like protein 2.	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Vang-like protein 2.	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Vang-like protein 2.	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Vang-like protein 2.	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Vang-like protein 2.	[11]

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] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] 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.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.