Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAXC9CB)

• DOT Name: Protein canopy homolog 3 (CNPY3)
• Synonyms: CTG repeat protein 4a; Expanded repeat-domain protein CAG/CTG 5; Protein associated with TLR4; Trinucleotide repeat-containing gene 5 protein
• Gene Name: CNPY3
• Related Disease:
  West syndrome
  Developmental and epileptic encephalopathy, 60
• UniProt ID: CNPY3_HUMAN
• Pfam ID: PF11938
• Sequence:
  MDSMPEPASRCLLLLPLLLLLLLLLPAPELGPSQAGAEENDWVRLPSKCEVCKYVAVELK
  SAFEETGKTKEVIGTGYGILDQKASGVKYTKSDLRLIEVTETICKRLLDYSLHKERTGSN
  RFAKGMSETFETLHNLVHKGVKVVMDIPYELWNETSAEVADLKKQCDVLVEEFEEVIEDW
  YRNHQEEDLTEFLCANHVLKGKDTSCLAEQWSGKKGDTAALGGKKSKKKSSRAKAAGGRS
  SSSKQRKELGGLEGDPSPEEDEGIQKASPLTHSPPDEL
• Function: Toll-like receptor (TLR)-specific co-chaperone for HSP90B1. Required for proper TLR folding, except that of TLR3, and hence controls TLR exit from the endoplasmic reticulum. Consequently, required for both innate and adaptive immune responses.
• Reactome Pathway: Trafficking and processing of endosomal TLR (R-HSA-1679131)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
West syndrome	DISLIAU9	Supportive	Autosomal dominant	[1]
Developmental and epileptic encephalopathy, 60	DIS5VU3A	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein canopy homolog 3 (CNPY3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein canopy homolog 3 (CNPY3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein canopy homolog 3 (CNPY3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein canopy homolog 3 (CNPY3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein canopy homolog 3 (CNPY3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein canopy homolog 3 (CNPY3).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein canopy homolog 3 (CNPY3).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein canopy homolog 3 (CNPY3).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein canopy homolog 3 (CNPY3).	[9]

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 affects the methylation of Protein canopy homolog 3 (CNPY3).	[10]

References

• [1] Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy. Am J Hum Genet. 2018 Feb 1;102(2):321-329. doi: 10.1016/j.ajhg.2018.01.004. Epub 2018 Jan 27.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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.