Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT2ESR4)

• DOT Name: Uncharacterized protein C5orf34 (C5ORF34)
• Gene Name: C5ORF34
• Related Disease:
  Leukocyte adhesion deficiency type 1
  Lung adenocarcinoma
• UniProt ID: CE034_HUMAN
• Pfam ID: PF15016 ; PF15025
• Sequence:
  MAAELRMILYEDDSVQVQYVDGSTLQLSPCGSEFLFEKSPPVSAHPLEQPERIRQRTHFV
  ISTYREQLQRALDFRNSSATCPFLSETIIPSERKKHIFIDITEVRWPSLDTDGTMIYMES
  GIVKITSLDGHAYLCLPRSQHEFTVHFLCKVSQKSDSSAVLSETNNKAPKDKLVEKTGKI
  CIRGNLPGQRLKNKENEFHCQIMKSKETLKKMSCVNGTEGREELPSPGTKHTCVYTWVKQ
  CWSVAACPEEWKYPLSLALHFHNKISNMSKIDAHITQSRFLTSDISEERGKVVSVLPRAL
  SLSCPVPHLHRWNFCDSLLQRQSDEYSYPELVKMVWYKGVTYRLTHQNMNSIEIYSGDGS
  VFKSEGAYFGNYFTYYSIQEGSGKREEKTYSVNNLPPDRPGSPFTVGSLIKQATRILQHC
  VKMRLSLSHNYRICCWKMVPGINDSNILPLVLKESLIPSVGRFLAYSDDKVHAIFLDGIT
  LTLNWNFSSPIEKRQVNQGLNLGWCKLTFPDGQEQLIQIEHPEPYERYVTTVTSWCRRLT
  QTSPREMPTHSSSSVLQENWSVASELEKIQKFNLLLENSGILNQISNKKNEQQSFDHYKP
  GSSETLLGEVNENRVSIALKKTSEILHDIDCLLSNSKK

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukocyte adhesion deficiency type 1	DISA1J7W	Strong	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]

19 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 Uncharacterized protein C5orf34 (C5ORF34).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[11]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[18]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Uncharacterized protein C5orf34 (C5ORF34).	[10]

References

• [1] Up-regulation of C5orf34 promotes lung adenocarcinoma migration and is correlated with worse prognosis.Gene. 2019 May 15;696:47-53. doi: 10.1016/j.gene.2019.02.019. Epub 2019 Feb 13.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [10] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [11] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [12] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.