Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU0R1CU)

• DOT Name: Glucocorticoid-induced transcript 1 protein (GLCCI1)
• Gene Name: GLCCI1
• Related Disease:
  OPTN-related open angle glaucoma
  Acute coronary syndrome
  Nephrotic syndrome
  Seasonal allergic rhinitis
  Acute graft versus host disease
  Graft-versus-host disease
  High blood pressure
  Acute myelogenous leukaemia
  Asthma
  Bone osteosarcoma
  Glaucoma/ocular hypertension
  Osteosarcoma
  Rheumatoid arthritis
• UniProt ID: GLCI1_HUMAN
• Pfam ID: PF15388
• Sequence:
  MSTASSSSSSSSSQTPHPPSQRMRRSAAGSPPAVAAAGSGNGAGGGGGVGCAPAAGAGRL
  LQPIRATVPYQLLRGSQHSPTRPPVAAAAASLGSLPGPGAARGPSPSSPTPPAAAAPAEQ
  APRAKGRPRRSPESHRRSSSPERRSPGSPVCRADKAKSQQVRTSSTIRRTSSLDTITGPY
  LTGQWPRDPHVHYPSCMKDKATQTPSCWAEEGAEKRSHQRSASWGSADQLKEQIAKLRQQ
  LQRSKQSSRHSKEKDRQSPLHGNHITISHTQATGSRSVPMPLSNISVPKSSVSRVPCNVE
  GISPELEKVFIKENNGKEEVSKPLDIPDGRRAPLPAHYRSSSTRSIDTQTPSVQERSSSC
  SSHSPCVSPFCPPESQDGSPCSTEDLLYDRDKDSGSSSPLPKYASSPKPNNSYMFKREPP
  EGCERVKVFEEMASRQPISAPLFSCPDKNKVNFIPTGSAFCPVKLLGPLLPASDLMLKNS
  PNSGQSSALATLTVEQLSSRVSFTSLSDDTSTAGSMEASVQQPSQQQQLLQELQGEDHIS
  AQNYVII
• Tissue Specificity: Predominantly expressed in lung, spleen, thymus and testis and, at lower levels, in brain, bone marrow, peripheral leukocytes, skin and trachea.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[1]
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[2]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[3]
Seasonal allergic rhinitis	DIS58KQX	Strong	Biomarker	[4]
Acute graft versus host disease	DIS8KLVM	moderate	Genetic Variation	[5]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[5]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[7]
Asthma	DISW9QNS	Limited	Genetic Variation	[8]
Bone osteosarcoma	DIST1004	Limited	Genetic Variation	[9]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Genetic Variation	[10]
Osteosarcoma	DISLQ7E2	Limited	Genetic Variation	[9]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[11]

17 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 Glucocorticoid-induced transcript 1 protein (GLCCI1).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[18]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[20]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[21]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[22]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[22]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[26]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Glucocorticoid-induced transcript 1 protein (GLCCI1).	[29]

References

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• [3] GLCCI1 single nucleotide polymorphisms in pediatric nephrotic syndrome.Pediatr Nephrol. 2012 Sep;27(9):1595-9. doi: 10.1007/s00467-012-2197-6. Epub 2012 Jun 4.
• [4] Glucocorticoid-Induced Transcription Factor 1 (GLCCI1) Variant Impacts the Short-Term Response to Intranasal Corticosteroids in Chinese Han Patients with Seasonal Allergic Rhinitis.Med Sci Monit. 2018 Jul 7;24:4691-4697. doi: 10.12659/MSM.908814.
• [5] GLCCI1 and Glucocorticoid Receptor Genetic Diversity and Response to Glucocorticoid-Based Treatment of Graft-versus-Host Disease.Biol Blood Marrow Transplant. 2015 Jul;21(7):1246-50. doi: 10.1016/j.bbmt.2015.03.015. Epub 2015 Apr 3.
• [6] Association Between GLCCI1 Promoter Polymorphism (Rs37972) and Post-Transplant Hypertension in Renal Transplant Recipients.Kidney Blood Press Res. 2017;42(6):1155-1163. doi: 10.1159/000485862. Epub 2017 Dec 8.
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• [8] GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids.J Investig Allergol Clin Immunol. 2018;28(3):165-171. doi: 10.18176/jiaci.0229. Epub 2018 Jan 17.
• [9] Identification of miRNA and genes involving in osteosarcoma by comprehensive analysis of microRNA and copy number variation data.Oncol Lett. 2017 Nov;14(5):5427-5433. doi: 10.3892/ol.2017.6845. Epub 2017 Aug 28.
• [10] Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus.Hum Mol Genet. 2013 Nov 15;22(22):4653-60. doi: 10.1093/hmg/ddt293. Epub 2013 Jul 7.
• [11] Polymorphisms in the glucocorticoid receptor gene and in the glucocorticoid-induced transcript 1 gene are associated with disease activity and response to glucocorticoid bridging therapy in rheumatoid arthritis.Rheumatol Int. 2015 Aug;35(8):1325-33. doi: 10.1007/s00296-015-3235-z. Epub 2015 Feb 28.
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• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [18] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [19] 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.
• [20] 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.
• [21] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [22] 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.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [25] 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.
• [26] 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.
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• [28] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [29] 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.