Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC7FRXL)

• DOT Name: Intron Large complex component GCFC2 (GCFC2)
• Synonyms: GC-rich sequence DNA-binding factor; GC-rich sequence DNA-binding factor 2; Transcription factor 9; TCF-9
• Gene Name: GCFC2
• Related Disease:
  Acute myocardial infarction
  Carcinoma
  Childhood acute lymphoblastic leukemia
  Gastric adenocarcinoma
  Periodontal disease
  Periodontitis
  Plasma cell myeloma
  Squamous cell carcinoma
  T-cell lymphoma
  Acute myelogenous leukaemia
  Rheumatoid arthritis
• UniProt ID: GCFC2_HUMAN
• Pfam ID: PF07842
• Sequence:
  MAHRPKRTFRQRAADSSDSDGAEESPAEPGAPRELPVPGSAEEEPPSGGGRAQVAGLPHR
  VRGPRGRGRVWASSRRATKAAPRADEGSESRTLDVSTDEEDKIHHSSESKDDQGLSSDSS
  SSLGEKELSSTVKIPDAAFIQAARRKRELARAQDDYISLDVQHTSSISGMKRESEDDPES
  EPDDHEKRIPFTLRPQTLRQRMAEESISRNEETSEESQEDEKQDTWEQQQMRKAVKIIEE
  RDIDLSCGNGSSKVKKFDTSISFPPVNLEIIKKQLNTRLTLLQETHRSHLREYEKYVQDV
  KSSKSTIQNLESSSNQALNCKFYKSMKIYVENLIDCLNEKIINIQEIESSMHALLLKQAM
  TFMKRRQDELKHESTYLQQLSRKDETSTSGNFSVDEKTQWILEEIESRRTKRRQARVLSG
  NCNHQEGTSSDDELPSAEMIDFQKSQGDILQKQKKVFEEVQDDFCNIQNILLKFQQWREK
  FPDSYYEAFISLCIPKLLNPLIRVQLIDWNPLKLESTGLKEMPWFKSVEEFMDSSVEDSK
  KESSSDKKVLSAIINKTIIPRLTDFVEFLWDPLSTSQTTSLITHCRVILEEHSTCENEVS
  KSRQDLLKSIVSRMKKAVEDDVFIPLYPKSAVENKTSPHSKFQERQFWSGLKLFRNILLW
  NGLLTDDTLQELGLGKLLNRYLIIALLNATPGPDVVKKCNQVAACLPEKWFENSAMRTSI
  PQLENFIQFLLQSAHKLSRSEFRDEVEEIILILVKIKALNQAESFIGEHHLDHLKSLIKE
  D
• Function: Involved in pre-mRNA splicing through regulating spliceosome C complex formation. May play a role during late-stage splicing events and turnover of excised introns.
• Tissue Specificity: Widely expressed in tissues and cell lines.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[3]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[4]
Periodontal disease	DISJQHVN	Strong	Genetic Variation	[1]
Periodontitis	DISI9JOI	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[2]
T-cell lymphoma	DISSXRTQ	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[6]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[7]

12 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 Intron Large complex component GCFC2 (GCFC2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Intron Large complex component GCFC2 (GCFC2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Intron Large complex component GCFC2 (GCFC2).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Intron Large complex component GCFC2 (GCFC2).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Intron Large complex component GCFC2 (GCFC2).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Intron Large complex component GCFC2 (GCFC2).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Intron Large complex component GCFC2 (GCFC2).	[15]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Intron Large complex component GCFC2 (GCFC2).	[16]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 increases the expression of Intron Large complex component GCFC2 (GCFC2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Intron Large complex component GCFC2 (GCFC2).	[18]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Intron Large complex component GCFC2 (GCFC2).	[20]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Intron Large complex component GCFC2 (GCFC2).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Intron Large complex component GCFC2 (GCFC2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Intron Large complex component GCFC2 (GCFC2).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Intron Large complex component GCFC2 (GCFC2).	[19]

References

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• [2] Expression and chromosomal localization of the gene for the human transcriptional repressor GCF.J Biol Chem. 1992 Jan 25;267(3):1689-94.
• [3] Genome-wide association study of childhood acute lymphoblastic leukemia in Korea.Leuk Res. 2010 Oct;34(10):1271-4. doi: 10.1016/j.leukres.2010.02.001. Epub 2010 Feb 26.
• [4] The Gastric Microbiome Is Perturbed in Advanced Gastric Adenocarcinoma Identified Through Shotgun Metagenomics.Front Cell Infect Microbiol. 2018 Dec 12;8:433. doi: 10.3389/fcimb.2018.00433. eCollection 2018.
• [5] Peri-Implantitis Diagnosis and Prognosis Using Biomarkers in Peri-Implant Crevicular Fluid: A Narrative Review.Diagnostics (Basel). 2019 Dec 7;9(4):214. doi: 10.3390/diagnostics9040214.
• [6] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [7] Effects of non-surgical periodontal therapy on periodontal laboratory and clinical data as well as on disease activity in patients with rheumatoid arthritis.Clin Oral Investig. 2019 Jan;23(1):141-151. doi: 10.1007/s00784-018-2420-3. Epub 2018 Mar 27.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] 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.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] 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.
• [13] 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.
• [14] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [18] 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.
• [19] 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.
• [20] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.
• [21] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.