Details of Drug Off-Target (DOT)

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

• DOT Name: Condensin-2 complex subunit G2 (NCAPG2)
• Synonyms: Chromosome-associated protein G2; CAP-G2; hCAP-G2; Leucine zipper protein 5; Non-SMC condensin II complex subunit G2
• Gene Name: NCAPG2
• Related Disease:
  Drug-resistant tuberculosis
  Hepatocellular carcinoma
  Acute myocardial infarction
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Lung adenocarcinoma
  Meningeal tuberculosis
  Multi-drug resistant tuberculosis
  Myocardial infarction
  Neoplasm
  Parkinson disease
  Pulmonary tuberculosis
  Schizophrenia
  Type-1/2 diabetes
  Isolated congenital microcephaly
  Khan-Khan-Katsanis syndrome
  Pleural tuberculosis
• UniProt ID: CNDG2_HUMAN
• Pfam ID: PF12422
• Sequence:
  MEKRETFVQAVSKELVGEFLQFVQLDKEASDPFSLNELLDELSRKQKEELWQRLKNLLTD
  VLLESPVDGWQVVEAQGEDNMETEHGSKMRKSIEIIYAITSVILASVSVINESENYEALL
  ECVIILNGILYALPESERKLQSSIQDLCVTWWEKGLPAKEDTGKTAFVMLLRRSLETKTG
  ADVCRLWRIHQALYCFDYDLEESGEIKDMLLECFININYIKKEEGRRFLSCLFNWNINFI
  KMIHGTIKNQLQGLQKSLMVYIAEIYFRAWKKASGKILEAIENDCIQDFMFHGIHLPRRS
  PVHSKVREVLSYFHHQKKVRQGVEEMLYRLYKPILWRGLKARNSEVRSNAALLFVEAFPI
  RDPNLHAIEMDSEIQKQFEELYSLLEDPYPMVRSTGILGVCKITSKYWEMMPPTILIDLL
  KKVTGELAFDTSSADVRCSVFKCLPMILDNKLSHPLLEQLLPALRYSLHDNSEKVRVAFV
  DMLLKIKAVRAAKFWKICPMEHILVRLETDSRPVSRRLVSLIFNSFLPVNQPEEVWCERC
  VTLVQMNHAAARRFYQYAHEHTACTNIAKLIHVIRHCLNACIQRAVREPPEDEEEEDGRE
  KENVTVLDKTLSVNDVACMAGLLEIIVILWKSIDRSMENNKEAKLYTINKFASVLPEYLK
  VFKDDRCKIPLFMLMSFMPASAVPPFSCGVISTLRSREEGAVDKSYCTLLDCLCSWGQVG
  HILELVDNWLPTEHAQAKSNTASKGRVQIHDTRPVKPELALVYIEYLLTHPKNRECLLSA
  PRKKLNHLLKALETSKADLESLLQTPGGKPRGFSEAAAPRAFGLHCRLSIHLQHKFCSEG
  KVYLSMLEDTGFWLESKILSFIQDQEEDYLKLHRVIYQQIIQTYLTVCKDVVMVGLGDHQ
  FQMQLLQRSLGIMQTVKGFFYVSLLLDILKEITGSSLIQKTDSDEEVAMLLDTVQKVFQK
  MLECIARSFRKQPEEGLRLLYSVQRPLHEFITAVQSRHTDTPVHRGVLSTLIAGPVVEIS
  HQLRKVSDVEELTPPEHLSDLPPFSRCLIGIIIKSSNVVRSFLDELKACVASNDIEGIVC
  LTAAVHIILVINAGKHKSSKVREVAATVHRKLKTFMEITLEEDSIERFLYESSSRTLGEL
  LNS
• Function: Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis.
• Reactome Pathway: Condensation of Prophase Chromosomes (R-HSA-2299718)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Drug-resistant tuberculosis	DIS5BUFB	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[2]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Meningeal tuberculosis	DIS8KHDE	Strong	Biomarker	[6]
Multi-drug resistant tuberculosis	DIS1A2CS	Strong	Biomarker	[7]
Myocardial infarction	DIS655KI	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Parkinson disease	DISQVHKL	Strong	Biomarker	[8]
Pulmonary tuberculosis	DIS6FLUM	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[10]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[11]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[12]
Khan-Khan-Katsanis syndrome	DISLKX2S	Limited	Autosomal recessive	[13]
Pleural tuberculosis	DISD09EG	Limited	Biomarker	[14]

20 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 Condensin-2 complex subunit G2 (NCAPG2).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[20]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Condensin-2 complex subunit G2 (NCAPG2).	[23]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[24]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[25]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[26]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[27]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[28]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[29]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[30]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Condensin-2 complex subunit G2 (NCAPG2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Condensin-2 complex subunit G2 (NCAPG2).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Condensin-2 complex subunit G2 (NCAPG2).	[34]

References

• [1] Abbott RealTime MTB and MTB RIF/INH assays for the diagnosis of tuberculosis and rifampicin/isoniazid resistance.Infect Genet Evol. 2019 Jul;71:54-59. doi: 10.1016/j.meegid.2019.03.012. Epub 2019 Mar 20.
• [2] NCAPG2 overexpression promotes hepatocellular carcinoma proliferation and metastasis through activating the STAT3 and NF-B/miR-188-3p pathways.EBioMedicine. 2019 Jun;44:237-249. doi: 10.1016/j.ebiom.2019.05.053. Epub 2019 Jun 5.
• [3] Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review.Clin Lymphoma Myeloma Leuk. 2020 Jan;20(1):18-23. doi: 10.1016/j.clml.2019.08.008. Epub 2019 Aug 26.
• [4] NCAPG2 promotes tumour proliferation by regulating G2/M phase and associates with poor prognosis in lung adenocarcinoma.J Cell Mol Med. 2017 Apr;21(4):665-676. doi: 10.1111/jcmm.13010. Epub 2016 Nov 15.
• [5] Re-expression of miR-200c suppresses proliferation, colony formation and in vivo tumor growth of murine claudin-low mammary tumor cells.Oncotarget. 2017 Apr 4;8(14):23727-23749. doi: 10.18632/oncotarget.15829.
• [6] Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid.J Infect. 2017 Aug;75(2):125-131. doi: 10.1016/j.jinf.2017.04.010. Epub 2017 May 10.
• [7] Design, synthesis and in vitro anti-mycobacterial activities of homonuclear and heteronuclear bis-isatin derivatives.Fitoterapia. 2018 Jun;127:383-386. doi: 10.1016/j.fitote.2018.03.018. Epub 2018 Apr 6.
• [8] Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls.Neurobiol Aging. 2015 Feb;36(2):1105-9. doi: 10.1016/j.neurobiolaging.2014.10.039. Epub 2014 Nov 5.
• [9] IP-10 dried blood spots assay monitoring treatment efficacy in extrapulmonary tuberculosis in a low-resource setting.Sci Rep. 2019 Mar 7;9(1):3871. doi: 10.1038/s41598-019-40458-0.
• [10] Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms: Effects on Antipsychotic Response and Schizophrenia Psychopathology in a Naturalistic Treatment Setting in Two Independent Korean and Italian Samples.Adv Ther. 2017 Jun;34(6):1482-1497. doi: 10.1007/s12325-017-0555-2. Epub 2017 May 16.
• [11] Operationalization of bi-directional screening for tuberculosis and diabetes in private sector healthcare clinics in Karachi, Pakistan.BMC Health Serv Res. 2019 Mar 6;19(1):147. doi: 10.1186/s12913-019-3975-7.
• [12] Combined deletion of two Condensin II system genes (NCAPG2 and MCPH1) in a case of severe microcephaly and mental deficiency. Eur J Med Genet. 2013 Nov;56(11):635-41. doi: 10.1016/j.ejmg.2013.07.007. Epub 2013 Sep 4.
• [13] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [14] Evaluation of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural tuberculosis in a high prevalence HIV/TB setting.PLoS One. 2014 Jul 22;9(7):e102702. doi: 10.1371/journal.pone.0102702. eCollection 2014.
• [15] 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.
• [16] 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.
• [17] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [18] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] 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.
• [21] 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.
• [22] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [23] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [24] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [25] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [26] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [27] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [28] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [29] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [30] 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.
• [31] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [32] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [33] 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.
• [34] 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.