Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR7VRAK)

DOT Name Solute carrier family 12 member 9 (SLC12A9)
Synonyms Cation-chloride cotransporter 6; hCCC6; Cation-chloride cotransporter-interacting protein 1; CCC-interacting protein 1; hCIP1; Potassium-chloride transporter 9; WO3.3
Gene Name SLC12A9
Related Disease
Classic Hodgkin lymphoma ( )
Lung adenocarcinoma ( )
Urinary bladder neoplasm ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Brain neoplasm ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Esophageal squamous cell carcinoma ( )
Glioblastoma multiforme ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
High blood pressure ( )
leukaemia ( )
Leukemia ( )
Neoplasm of esophagus ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Oral cancer ( )
Osteosarcoma ( )
Ovarian neoplasm ( )
Pancreatic adenocarcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
Tarsal-carpal coalition syndrome ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Endometrial carcinoma ( )
Glioma ( )
Pancreatic cancer ( )
Melanoma ( )
Carcinoma of esophagus ( )
Clear cell renal carcinoma ( )
Esophageal cancer ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Primary biliary cholangitis ( )
Systemic lupus erythematosus ( )
UniProt ID
S12A9_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00324 ; PF03522
Sequence
MASESSPLLAYRLLGEEGVALPANGAGGPGGASARKLSTFLGVVVPTVLSMFSIVVFLRI
GFVVGHAGLLQALAMLLVAYFILALTVLSVCAIATNGAVQGGGAYFMISRTLGPEVGGSI
GLMFYLANVCGCAVSLLGLVESVLDVFGADATGPSGLRVLPQGYGWNLLYGSLLLGLVGG
VCTLGAGLYARASFLTFLLVSGSLASVLISFVAVGPRDIRLTPRPGPNGSSLPPRFGHFT
GFNSSTLKDNLGAGYAEDYTTGAVMNFASVFAVLFNGCTGIMAGANMSGELKDPSRAIPL
GTIVAVAYTFFVYVLLFFLSSFTCDRTLLQEDYGFFRAISLWPPLVLIGIYATALSASMS
SLIGASRILHALARDDLFGVILAPAKVVSRGGNPWAAVLYSWGLVQLVLLAGKLNTLAAV
VTVFYLVAYAAVDLSCLSLEWASAPNFRPTFSLFSWHTCLLGVASCLLMMFLISPGAAGG
SLLLMGLLAALLTARGGPSSWGYVSQALLFHQVRKYLLRLDVRKDHVKFWRPQLLLLVGN
PRGALPLLRLANQLKKGGLYVLGHVTLGDLDSLPSDPVQPQYGAWLSLVDRAQVKAFVDL
TLSPSVRQGAQHLLRISGLGGMKPNTLVLGFYDDAPPQDHFLTDPAFSEPADSTREGSSP
ALSTLFPPPRAPGSPRALNPQDYVATVADALKMNKNVVLARASGALPPERLSRGSGGTSQ
LHHVDVWPLNLLRPRGGPGYVDVCGLFLLQMATILGMVPAWHSARLRIFLCLGPREAPGA
AEGRLRALLSQLRIRAEVQEVVWGEGAGAGEPEAEEEGDFVNSGRGDAEAEALARSANAL
VRAQQGRGTGGGPGGPEGGDAEGPITALTFLYLPRPPADPARYPRYLALLETLTRDLGPT
LLVHGVTPVTCTDL
Function May be an inhibitor of SLC12A1. Seems to correspond to a subunit of a multimeric transport system and thus, additional subunits may be required for its function.
Tissue Specificity Highly expressed in placenta, brain and kidney. Lower expression in lung, liver and heart.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Classic Hodgkin lymphoma DISV1LU6 Definitive Altered Expression [1]
Lung adenocarcinoma DISD51WR Definitive Altered Expression [2]
Urinary bladder neoplasm DIS7HACE Definitive Biomarker [3]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [4]
Adenocarcinoma DIS3IHTY Strong Biomarker [5]
Adult glioblastoma DISVP4LU Strong Altered Expression [6]
Advanced cancer DISAT1Z9 Strong Biomarker [7]
Bladder cancer DISUHNM0 Strong Biomarker [3]
Bone osteosarcoma DIST1004 Strong Biomarker [8]
Brain neoplasm DISY3EKS Strong Genetic Variation [9]
Cervical cancer DISFSHPF Strong Biomarker [10]
Cervical carcinoma DIST4S00 Strong Biomarker [10]
Colon cancer DISVC52G Strong Altered Expression [11]
Colon carcinoma DISJYKUO Strong Altered Expression [11]
Colonic neoplasm DISSZ04P Strong Altered Expression [12]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [13]
Esophageal squamous cell carcinoma DIS5N2GV Strong Genetic Variation [14]
Glioblastoma multiforme DISK8246 Strong Altered Expression [6]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [15]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [16]
High blood pressure DISY2OHH Strong Genetic Variation [17]
leukaemia DISS7D1V Strong Altered Expression [4]
Leukemia DISNAKFL Strong Altered Expression [4]
Neoplasm of esophagus DISOLKAQ Strong Genetic Variation [18]
Neuroblastoma DISVZBI4 Strong Altered Expression [19]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [20]
Oral cancer DISLD42D Strong Genetic Variation [21]
Osteosarcoma DISLQ7E2 Strong Biomarker [8]
Ovarian neoplasm DISEAFTY Strong Altered Expression [22]
Pancreatic adenocarcinoma DISKHX7S Strong Altered Expression [23]
Prostate cancer DISF190Y Strong Biomarker [24]
Prostate carcinoma DISMJPLE Strong Biomarker [24]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [25]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [26]
Tarsal-carpal coalition syndrome DISY90L2 Strong Biomarker [27]
Ulcerative colitis DIS8K27O Strong Biomarker [28]
Urinary bladder cancer DISDV4T7 Strong Biomarker [3]
Endometrial carcinoma DISXR5CY moderate Biomarker [29]
Glioma DIS5RPEH moderate Biomarker [30]
Pancreatic cancer DISJC981 moderate Altered Expression [31]
Melanoma DIS1RRCY Disputed Altered Expression [32]
Carcinoma of esophagus DISS6G4D Limited Genetic Variation [18]
Clear cell renal carcinoma DISBXRFJ Limited Biomarker [25]
Esophageal cancer DISGB2VN Limited Genetic Variation [18]
Head and neck cancer DISBPSQZ Limited Biomarker [33]
Head and neck carcinoma DISOU1DS Limited Biomarker [33]
Primary biliary cholangitis DIS43E0O Limited Biomarker [34]
Systemic lupus erythematosus DISI1SZ7 Limited Genetic Variation [35]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Solute carrier family 12 member 9 (SLC12A9). [36]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Solute carrier family 12 member 9 (SLC12A9). [37]
Menadione DMSJDTY Approved Menadione affects the expression of Solute carrier family 12 member 9 (SLC12A9). [38]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of Solute carrier family 12 member 9 (SLC12A9). [39]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Solute carrier family 12 member 9 (SLC12A9). [41]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Solute carrier family 12 member 9 (SLC12A9). [40]
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References

1 Retinoblastoma gene product and P21 (WAF1, CIP1) protein expression in non Hodgkin's lymphomas: a multivariate survival analysis.Leuk Lymphoma. 2001 Feb;40(5-6):647-58. doi: 10.3109/10428190109097662.
2 MiR-224 promotes the chemoresistance of human lung adenocarcinoma cells to cisplatin via regulating G?S transition and apoptosis by targeting p21(WAF1/CIP1).Br J Cancer. 2014 Jul 15;111(2):339-54. doi: 10.1038/bjc.2014.157. Epub 2014 Jun 12.
3 Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in patients with T1 bladder tumours: clinical implications and prognostic significance.Actas Urol Esp. 2017 Apr;41(3):172-180. doi: 10.1016/j.acuro.2016.09.003. Epub 2016 Oct 7.
4 Transcriptional upregulation of p21/WAF/Cip1 in myeloid leukemic blasts expressing AML1-ETO.Haematologica. 2008 Nov;93(11):1728-33. doi: 10.3324/haematol.13044. Epub 2008 Sep 11.
5 Dual and opposing roles of ERK in regulating G(1) and S-G(2)/M delays in A549 cells caused by hyperoxia.Exp Cell Res. 2004 Jul 15;297(2):472-83. doi: 10.1016/j.yexcr.2004.03.033.
6 P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in vivo.J Agric Food Chem. 2013 Mar 20;61(11):2811-9. doi: 10.1021/jf400542m. Epub 2013 Mar 7.
7 Epigenetic Regulation of p21(cip1/waf1) in Human Cancer.Cancers (Basel). 2019 Sep 11;11(9):1343. doi: 10.3390/cancers11091343.
8 The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.PLoS One. 2015 Jun 2;10(6):e0128513. doi: 10.1371/journal.pone.0128513. eCollection 2015.
9 Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines.Mol Cancer Ther. 2008 Jun;7(6):1461-71. doi: 10.1158/1535-7163.MCT-07-2010.
10 Human papillomavirus E7 oncoprotein overrides the tumor suppressor activity of p21Cip1 in cervical carcinogenesis.Cancer Res. 2009 Jul 15;69(14):5656-63. doi: 10.1158/0008-5472.CAN-08-3711. Epub 2009 Jul 7.
11 Atypical role of sprouty in p21 dependent inhibition of cell proliferation in colorectal cancer.Mol Carcinog. 2016 Sep;55(9):1355-68. doi: 10.1002/mc.22379. Epub 2015 Aug 21.
12 Molecular alterations associated with sulindac-resistant colon tumors in ApcMin/+ mice.Cancer Prev Res (Phila). 2010 Sep;3(9):1187-97. doi: 10.1158/1940-6207.CAPR-09-0270. Epub 2010 Aug 17.
13 Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of colorectal cancer through regulating chaperone mediated autophagy degradation of p21(Cip1/WAF1).Cancer Lett. 2018 Apr 10;419:116-127. doi: 10.1016/j.canlet.2018.01.045.
14 Polymorphism rs2395655 affects LEDGF/p75 binding activity and p21WAF1/CIP1 gene expression in esophageal squamous cell carcinoma.Cancer Med. 2019 May;8(5):2313-2324. doi: 10.1002/cam4.2067. Epub 2019 Mar 10.
15 Increased expression of stathmin and elongation factor 1 in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients.J Transl Med. 2014 May 31;12:154. doi: 10.1186/1479-5876-12-154.
16 Correction: Hepatitis C Virus Core Protein Down-Regulates p21Waf1/Cip1 and Inhibits Curcumin-Induced Apoptosis through MicroRNA-345 Targeting in Human Hepatoma Cells.PLoS One. 2017 Jul 7;12(7):e0181299. doi: 10.1371/journal.pone.0181299. eCollection 2017.
17 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.PLoS Genet. 2011 Feb 10;7(2):e1001300. doi: 10.1371/journal.pgen.1001300.
18 p21 Waf1/Cip1 polymorphisms and risk of esophageal cancer.Ann Surg Oncol. 2010 May;17(5):1453-8. doi: 10.1245/s10434-009-0882-x. Epub 2010 Jan 29.
19 Targeting ornithine decarboxylase impairs development of MYCN-amplified neuroblastoma.Cancer Res. 2009 Jan 15;69(2):547-53. doi: 10.1158/0008-5472.CAN-08-2968.
20 Hsa-miR-326 targets CCND1 and inhibits non-small cell lung cancer development.Oncotarget. 2016 Feb 16;7(7):8341-59. doi: 10.18632/oncotarget.7071.
21 Association of p53 and p21(CDKN1A/WAF1/CIP1) polymorphisms with oral cancer in Taiwan patients.Anticancer Res. 2007 May-Jun;27(3B):1559-64.
22 EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53.Cancer Lett. 2013 Aug 9;336(1):53-60. doi: 10.1016/j.canlet.2013.04.012. Epub 2013 Apr 18.
23 Increased stability of P21(WAF1/CIP1) mRNA is required for ROS/ERK-dependent pancreatic adenocarcinoma cell growth inhibition by pyrrolidine dithiocarbamate.Biochim Biophys Acta. 2006 Sep;1763(9):917-26. doi: 10.1016/j.bbamcr.2006.05.015. Epub 2006 Jun 6.
24 Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.Oncotarget. 2016 Jul 26;7(30):48011-48026. doi: 10.18632/oncotarget.10333.
25 Targeted p21(WAF1/CIP1) activation by miR-1236 inhibits cell proliferation and correlates with favorable survival in renal cell carcinoma.Urol Oncol. 2016 Feb;34(2):59.e23-34. doi: 10.1016/j.urolonc.2015.08.014. Epub 2015 Sep 28.
26 Gene transfer of a cell cycle modulator exerts anti-inflammatory effects in the treatment of arthritis.J Immunol. 2003 Nov 1;171(9):4913-9. doi: 10.4049/jimmunol.171.9.4913.
27 Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications.Virchows Arch. 2001 Mar;438(3):289-97. doi: 10.1007/s004280000289.
28 Cyclin D1 and p21 in ulcerative colitis-related inflammation and epithelial neoplasia: a study of aberrant expression and underlying mechanisms.Hum Pathol. 2003 Jun;34(6):580-8. doi: 10.1016/s0046-8177(03)00125-4.
29 The adult stem cell marker Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch-1 and p21WAF1/CIP1.Int J Cancer. 2011 Oct 15;129(8):2042-9. doi: 10.1002/ijc.25856. Epub 2011 Mar 4.
30 Axitinib induces senescence-associated cell death and necrosis in glioma cell lines: The proteasome inhibitor, bortezomib, potentiates axitinib-induced cytotoxicity in a p21(Waf/Cip1) dependent manner.Oncotarget. 2017 Jan 10;8(2):3380-3395. doi: 10.18632/oncotarget.13769.
31 Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia.Cancer Res. 2001 Dec 15;61(24):8830-7.
32 Overexpression of HMGB1 in melanoma predicts patient survival and suppression of HMGB1 induces cell cycle arrest and senescence in association with p21 (Waf1/Cip1) up-regulation via a p53-independent, Sp1-dependent pathway.Oncotarget. 2014 Aug 15;5(15):6387-403. doi: 10.18632/oncotarget.2201.
33 Reactive oxygen species and p21Waf1/Cip1 are both essential for p53-mediated senescence of head and neck cancer cells.Cell Death Dis. 2015 Mar 12;6(3):e1678. doi: 10.1038/cddis.2015.44.
34 A possible involvement of p62/sequestosome-1 in the process of biliary epithelial autophagy and senescence in primary biliary cirrhosis.Liver Int. 2012 Mar;32(3):487-99. doi: 10.1111/j.1478-3231.2011.02656.x. Epub 2011 Sep 27.
35 A regulatory SNP at position -899 in CDKN1A is associated with systemic lupus erythematosus and lupus nephritis.Genes Immun. 2009 Jul;10(5):482-6. doi: 10.1038/gene.2009.5. Epub 2009 Mar 5.
36 Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
37 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
38 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.
39 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
40 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.
41 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.