Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1YHLOR)

• DOT Name: Coiled-coil domain-containing protein 92 (CCDC92)
• Synonyms: Limkain beta-2
• Gene Name: CCDC92
• Related Disease:
  Atrial fibrillation
  Coronary heart disease
  Coronary atherosclerosis
  Non-insulin dependent diabetes
• UniProt ID: CCD92_HUMAN
• Pfam ID: PF14916
• Sequence:
  MTSPHFSSYDEGPLDVSMAATNLENQLHSAQKNLLFLQREHASTLKGLHSEIRRLQQHCT
  DLTYELTVKSSEQTGDGTSKSSELKKRCEELEAQLKVKENENAELLKELEQKNAMITVLE
  NTIKEREKKYLEELKAKSHKLTLLSSELEQRASTIAYLTSQLHAAKKKLMSSSGTSDASP
  SGSPVLASYKPAPPKDKLPETPRRRMKKSLSAPLHPEFEEVYRFGAESRKLLLREPVDAM
  PDPTPFLLARESAEVHLIKERPLVIPPIASDRSGEQHSPAREKPHKAHVGVAHRIHHATP
  PQAQPEVKTLAVDQVNGGKVVRKHSGTDRTV
• Function: Interferon-stimulated protein that plays a role in innate immunity. Strongly inhibits ebolavirus transcription and replication. Forms a complex with viral RNA-bound nucleocapsid NP and thereby prevents the transport of NP to the cell surface.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[2]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[4]

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 Coiled-coil domain-containing protein 92 (CCDC92).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Coiled-coil domain-containing protein 92 (CCDC92).	[17]

12 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 Coiled-coil domain-containing protein 92 (CCDC92).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil domain-containing protein 92 (CCDC92).	[18]

References

• [1] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [2] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [3] Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease.Nat Genet. 2017 Sep;49(9):1392-1397. doi: 10.1038/ng.3914. Epub 2017 Jul 17.
• [4] Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.Nat Genet. 2017 Oct;49(10):1450-1457. doi: 10.1038/ng.3943. Epub 2017 Sep 4.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [16] 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.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.