Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIR8URJ)

• DOT Name: Ashwin (C2ORF49)
• Gene Name: C2ORF49
• Related Disease: Atopic dermatitis
• UniProt ID: ASHWN_HUMAN
• Pfam ID: PF15323
• Sequence:
  MAGDVGGRSCTDSELLLHPELLSQEFLLLTLEQKNIAVETDVRVNKDSLTDLYVQHAIPL
  PQRDLPKNRWGKMMEKKREQHEIKNETKRSSTVDGLRKRPLIVFDGSSTSTSIKVKKTEN
  GDNDRLKPPPQASFTSNAFRKLSNSSSSVSPLILSSNLPVNNKTEHNNNDAKQNHDLTHR
  KSPSGPVKSPPLSPVGTTPVKLKRAAPKEEAEAMNNLKPPQAKRKIQHVTWP
• Reactome Pathway: tRNA processing in the nucleus (R-HSA-6784531)
• BioCyc Pathway: MetaCyc:ENSG00000135974-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ashwin (C2ORF49).	[2]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ashwin (C2ORF49).	[13]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Ashwin (C2ORF49).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ashwin (C2ORF49).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ashwin (C2ORF49).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ashwin (C2ORF49).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ashwin (C2ORF49).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ashwin (C2ORF49).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ashwin (C2ORF49).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ashwin (C2ORF49).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ashwin (C2ORF49).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ashwin (C2ORF49).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ashwin (C2ORF49).	[12]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Ashwin (C2ORF49).	[15]

References

• [1] Tiled array-based sequencing identifies enrichment of loss-of-function variants in the highly homologous filaggrin gene in African-American children with severe atopic dermatitis.Exp Dermatol. 2018 Sep;27(9):989-992. doi: 10.1111/exd.13691. Epub 2018 Jun 28.
• [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] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [15] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.