Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN13TYV)

• DOT Name: Protein ARV1 (ARV1)
• Synonyms: hARV1
• Gene Name: ARV1
• Related Disease:
  Developmental and epileptic encephalopathy, 38
  Non-alcoholic fatty liver disease
• UniProt ID: ARV1_HUMAN
• Pfam ID: PF04161
• Sequence:
  MGNGGRSGLQQGKGNVDGVAATPTAASASCQYRCIECNQEAKELYRDYNHGVLKITICKS
  CQKPVDKYIEYDPVIILINAILCKAQAYRHILFNTQINIHGKLCIFCLLCEAYLRWWQLQ
  DSNQNTAPDDLIRYAKEWDFYRMFAIAALEQTAYFIGIFTFLWVERPMTAKKKPNFILLL
  KALLLSSYGKLLLIPAVIWEHDYTSVCLKLIKVFVLTSNFQAIRVTLNINRKLSFLAVLS
  GLLLESIMVYFFQSMEWDVGSDYAIFKSQDF
• Function: Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis. Participates in sterol transport out of the ER and distribution into plasma membranes.
• Tissue Specificity: Ubiquitous. Highly expressed in liver and adipose.
• Reactome Pathway: Cholesterol biosynthesis (R-HSA-191273)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy, 38	DISHSSN4	Strong	Autosomal recessive	[1]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[2]

2 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 Protein ARV1 (ARV1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein ARV1 (ARV1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein ARV1 (ARV1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein ARV1 (ARV1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein ARV1 (ARV1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein ARV1 (ARV1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein ARV1 (ARV1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein ARV1 (ARV1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein ARV1 (ARV1).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Protein ARV1 (ARV1).	[12]

References

• [1] Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep. 2015 Jan 13;10(2):148-61. doi: 10.1016/j.celrep.2014.12.015. Epub 2014 Dec 31.
• [2] Mice lacking ARV1 have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease.J Biol Chem. 2018 Apr 20;293(16):5956-5974. doi: 10.1074/jbc.RA117.000800. Epub 2018 Feb 28.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.