Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQS84ZF)

DOT Name	Double-strand-break repair protein rad21 homolog (RAD21)
Synonyms	hHR21; Nuclear matrix protein 1; NXP-1; SCC1 homolog
Gene Name	RAD21
Related Disease	Cornelia de Lange syndrome ( ) Cornelia de Lange syndrome 4 ( ) Lung cancer ( ) Lung carcinoma ( ) Adenocarcinoma ( ) Bone osteosarcoma ( ) Cervical cancer ( ) Cervical carcinoma ( ) Chronic intestinal pseudoobstruction ( ) Colorectal carcinoma ( ) Congenital diaphragmatic hernia ( ) Head-neck squamous cell carcinoma ( ) Hepatitis C virus infection ( ) Laryngeal disorder ( ) Microcephaly ( ) Myeloid leukaemia ( ) Neoplasm ( ) Osteosarcoma ( ) Ovarian cancer ( ) Progressive multifocal leukoencephalopathy ( ) Promyelocytic leukaemia ( ) Ptosis ( ) Squamous cell carcinoma ( ) Thalassemia ( ) Turner syndrome ( ) Bladder cancer ( ) Carcinoma ( ) Hypoglycemia ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Breast cancer ( ) Breast carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Digestive system neoplasm ( ) Intellectual disability ( ) Mungan syndrome ( ) Prostate cancer ( ) Prostate carcinoma ( ) Sclerocornea ( ) Small lymphocytic lymphoma ( )
UniProt ID	RAD21_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	4PJU; 4PJW; 4PK7; 6QNX; 6RRC; 6RRK; 6WG3; 6WGE; 7W1M; 7ZJS
Pfam ID	PF04824 ; PF04825
Sequence	MFYAHFVLSKRGPLAKIWLAAHWDKKLTKAHVFECNLESSVESIISPKVKMALRTSGHLL LGVVRIYHRKAKYLLADCNEAFIKIKMAFRPGVVDLPEENREAAYNAITLPEEFHDFDQP LPDLDDIDVAQQFSLNQSRVEEITMREEVGNISILQENDFGDFGMDDREIMREGSAFEDD DMLVSTTTSNLLLESEQSTSNLNEKINHLEYEDQYKDDNFGEGNDGGILDDKLISNNDGG IFDDPPALSEAGVMLPEQPAHDDMDEDDNVSMGGPDSPDSVDPVEPMPTMTDQTTLVPNE EEAFALEPIDITVKETKAKRKRKLIVDSVKELDSKTIRAQLSDYSDIVTTLDLAPPTKKL MMWKETGGVEKLFSLPAQPLWNNRLLKLFTRCLTPLVPEDLRKRRKGGEADNLDEFLKEF ENPEVPREDQQQQHQQRDVIDEPIIEEPSRLQESVMEASRTNIDESAMPPPPPQGVKRKA GQIDPEPVMPPQQVEQMEIPPVELPPEEPPNICQLIPELELLPEKEKEKEKEKEDDEEEE DEDASGGDQDQEERRWNKRTQQMLHGLQRALAKTGAESISLLELCRNTNRKQAAAKFYSF LVLKKQQAIELTQEEPYSDIIATPGPRFHII
Function	[Double-strand-break repair protein rad21 homolog]: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions. The cohesin complex may also play a role in spindle pole assembly during mitosis. In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome. May control RUNX1 gene expression (Probable). Binds to and represses APOB gene promoter. May play a role in embryonic gut development, possibly through the regulation of enteric neuron development; [64-kDa C-terminal product]: May promote apoptosis.
Tissue Specificity	Expressed in the gut (at protein level).
KEGG Pathway	Cell cycle (hsa04110 )
Reactome Pathway	Separation of Sister Chromatids (R-HSA-2467813 ) Establishment of Sister Chromatid Cohesion (R-HSA-2468052 ) Cohesin Loading onto Chromatin (R-HSA-2470946 ) Resolution of Sister Chromatid Cohesion (R-HSA-2500257 ) SUMOylation of DNA damage response and repair proteins (R-HSA-3108214 ) Estrogen-dependent gene expression (R-HSA-9018519 ) Meiotic synapsis (R-HSA-1221632 )
BioCyc Pathway	MetaCyc:ENSG00000164754-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cornelia de Lange syndrome	DISEQSXO	Definitive	Autosomal dominant	[1]
Cornelia de Lange syndrome 4	DISXRJCA	Definitive	Autosomal dominant	[2]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[3]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Chronic intestinal pseudoobstruction	DISR68AN	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Congenital diaphragmatic hernia	DIS0IPVU	Strong	Genetic Variation	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Laryngeal disorder	DISDKUQO	Strong	Biomarker	[11]
Microcephaly	DIS2GRD8	Strong	Genetic Variation	[2]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[14]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[15]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[15]
Ptosis	DISJZNIY	Strong	Genetic Variation	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[16]
Thalassemia	DIS76XZB	Strong	Biomarker	[17]
Turner syndrome	DIS2035C	Strong	Biomarker	[17]
Bladder cancer	DISUHNM0	moderate	Biomarker	[18]
Carcinoma	DISH9F1N	moderate	Biomarker	[19]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[20]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[18]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[18]
Breast cancer	DIS7DPX1	Limited	Biomarker	[15]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[15]
Colon cancer	DISVC52G	Limited	Genetic Variation	[21]
Colon carcinoma	DISJYKUO	Limited	Genetic Variation	[21]
Digestive system neoplasm	DISPOJCT	Limited	Altered Expression	[22]
Intellectual disability	DISMBNXP	Limited	Biomarker	[23]
Mungan syndrome	DISNR0AY	Limited	Unknown	[24]
Prostate cancer	DISF190Y	Limited	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[25]
Sclerocornea	DIS7HV8A	Limited	Biomarker	[26]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[27]
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⏷ Show the Full List of 41 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Double-strand-break repair protein rad21 homolog (RAD21) affects the response to substance of Cisplatin.	[43]
Afimoxifene	DMFORDT	Phase 2	Double-strand-break repair protein rad21 homolog (RAD21) affects the response to substance of Afimoxifene.	[44]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[28]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[29]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[30]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[32]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[33]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[35]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[40]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[41]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Double-strand-break repair protein rad21 homolog (RAD21).	[42]
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⏷ Show the Full List of 12 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the methylation of Double-strand-break repair protein rad21 homolog (RAD21).	[31]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Double-strand-break repair protein rad21 homolog (RAD21).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Double-strand-break repair protein rad21 homolog (RAD21).	[37]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Double-strand-break repair protein rad21 homolog (RAD21).	[37]
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References

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2	A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 - Review of the literature. Eur J Med Genet. 2019 Jun;62(6):103526. doi: 10.1016/j.ejmg.2018.08.007. Epub 2018 Aug 17.
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11	Bioactive phytochemical proanthocyanidins inhibit growth of head and neck squamous cell carcinoma cells by targeting multiple signaling molecules.PLoS One. 2012;7(9):e46404. doi: 10.1371/journal.pone.0046404. Epub 2012 Sep 26.
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13	Evaluation of optical imaging agents in a fluorescence-guided surgical model of head and neck cancer.Surg Oncol. 2018 Jun;27(2):225-230. doi: 10.1016/j.suronc.2018.04.004. Epub 2018 Apr 26.
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18	DNA topoisomerase II and RAD21 cohesin complex component are predicted as potential therapeutic targets in bladder cancer.Oncol Lett. 2019 Jul;18(1):518-528. doi: 10.3892/ol.2019.10365. Epub 2019 May 17.
19	Enhanced RAD21 cohesin expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers.Breast Cancer Res. 2011 Jan 21;13(1):R9. doi: 10.1186/bcr2814.
20	Human rad21 gene, hHR21(SP), is downregulated by hypoxia in human tumor cells.Biochem Biophys Res Commun. 2001 Mar;281(5):1106-12. doi: 10.1006/bbrc.2001.4488.
21	Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers.J Cancer Res Clin Oncol. 2010 Feb;136(2):249-59. doi: 10.1007/s00432-009-0656-7. Epub 2009 Aug 12.
22	Cohesin Rad21 mediates loss of heterozygosity and is upregulated via Wnt promoting transcriptional dysregulation in gastrointestinal tumors.Cell Rep. 2014 Dec 11;9(5):1781-1797. doi: 10.1016/j.celrep.2014.10.059. Epub 2014 Nov 20.
23	Microcephaly-thin corpus callosum syndrome maps to 8q23.2-q24.12.Pediatr Neurol. 2012 Jun;46(6):363-8. doi: 10.1016/j.pediatrneurol.2012.03.014.
24	Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction. Gastroenterology. 2015 Apr;148(4):771-782.e11. doi: 10.1053/j.gastro.2014.12.034. Epub 2015 Jan 6.
25	TCEB1 promotes invasion of prostate cancer cells.Int J Cancer. 2009 Jan 1;124(1):95-102. doi: 10.1002/ijc.23916.
26	A Cohesin Subunit Variant Identified from a Peripheral Sclerocornea Pedigree.Dis Markers. 2019 Nov 12;2019:8781524. doi: 10.1155/2019/8781524. eCollection 2019.
27	Cohesin RAD21 Gene Promoter Methylation in Patients with Chronic Lymphocytic Leukemia.Cytogenet Genome Res. 2018;154(3):126-131. doi: 10.1159/000487868. Epub 2018 Mar 24.
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31	Analysis of the transcriptional regulation of cancer-related genes by aberrant DNA methylation of the cis-regulation sites in the promoter region during hepatocyte carcinogenesis caused by arsenic. Oncotarget. 2015 Aug 28;6(25):21493-506. doi: 10.18632/oncotarget.4085.
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35	Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73.
36	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.
37	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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