Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNSYUN6)

• DOT Name: Radixin (RDX)
• Gene Name: RDX
• Related Disease:
  Nonsyndromic genetic hearing loss
  Adult glioblastoma
  Advanced cancer
  Arthritis
  Autosomal recessive nonsyndromic hearing loss 24
  B-cell lymphoma
  Bone osteosarcoma
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Chordoma
  Colon cancer
  Colon carcinoma
  Deafness
  Diabetic kidney disease
  Dubin-Johnson syndrome
  Gastric cancer
  Glioblastoma multiforme
  Hepatitis
  Hepatocellular carcinoma
  Liver cancer
  Lung carcinoma
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-alcoholic steatohepatitis
  Osteosarcoma
  Pancreatic cancer
  Pancreatic tumour
  Postmenopausal osteoporosis
  Rheumatoid arthritis
  Stomach cancer
  Urticaria
  Lung adenocarcinoma
  Schwannoma
  Sensorineural hearing loss disorder
  Hearing loss, autosomal recessive
  Cholestasis
  Ankylosing spondylitis
  Crohn disease
  Meningioma
  Minimally invasive lung adenocarcinoma
  Neurofibromatosis type 2
  Primary biliary cholangitis
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: RADI_HUMAN
• Pfam ID: PF00769 ; PF20492 ; PF09380 ; PF00373 ; PF09379
• Sequence:
  MPKPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLK
  LNKKVTQQDVKKENPLQFKFRAKFFPEDVSEELIQEITQRLFFLQVKEAILNDEIYCPPE
  TAVLLASYAVQAKYGDYNKEIHKPGYLANDRLLPQRVLEQHKLTKEQWEERIQNWHEEHR
  GMLREDSMMEYLKIAQDLEMYGVNYFEIKNKKGTELWLGVDALGLNIYEHDDKLTPKIGF
  PWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKRILALCMGNHELYMRRRKPDTI
  EVQQMKAQAREEKHQKQLERAQLENEKKKREIAEKEKERIEREKEELMERLKQIEEQTIK
  AQKELEEQTRKALELDQERKRAKEEAERLEKERRAAEEAKSAIAKQAADQMKNQEQLAAE
  LAEFTAKIALLEEAKKKKEEEATEWQHKAFAAQEDLEKTKEELKTVMSAPPPPPPPPVIP
  PTENEHDEHDENNAEASAELSNEGVMNHRSEEERVTETQKNERVKKQLQALSSELAQARD
  ETKKTQNDVLHAENVKAGRDKYKTLRQIRQGNTKQRIDEFEAM
• Function: Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.
• KEGG Pathway:
  Tight junction (hsa04530)
  Regulation of actin cytoskeleton (hsa04810)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Recycling pathway of L1 (R-HSA-437239)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nonsyndromic genetic hearing loss	DISZX61P	Definitive	Autosomal recessive	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Arthritis	DIST1YEL	Strong	Biomarker	[4]
Autosomal recessive nonsyndromic hearing loss 24	DIS0P3E9	Strong	Autosomal recessive	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[9]
Chordoma	DISCHJE7	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Deafness	DISKCLH4	Strong	Genetic Variation	[12]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[13]
Dubin-Johnson syndrome	DISM8TG9	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Hepatitis	DISXXX35	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Liver cancer	DISDE4BI	Strong	Altered Expression	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[17]
Non-alcoholic steatohepatitis	DIST4788	Strong	Biomarker	[17]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Pancreatic cancer	DISJC981	Strong	Biomarker	[18]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[19]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[20]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Urticaria	DIS9WQAI	Strong	Biomarker	[21]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[22]
Schwannoma	DISTTVLA	moderate	Biomarker	[23]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[24]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[25]
Cholestasis	DISDJJWE	Disputed	Altered Expression	[26]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[27]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[27]
Meningioma	DISPT4TG	Limited	Biomarker	[28]
Minimally invasive lung adenocarcinoma	DIS4W83X	Limited	Altered Expression	[29]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[30]
Primary biliary cholangitis	DIS43E0O	Limited	Biomarker	[31]
Prostate cancer	DISF190Y	Limited	Biomarker	[32]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[32]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[27]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[27]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[27]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Radixin (RDX) affects the response to substance of Topotecan.	[47]

13 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 Radixin (RDX).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Radixin (RDX).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Radixin (RDX).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Radixin (RDX).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Radixin (RDX).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Radixin (RDX).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Radixin (RDX).	[39]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Radixin (RDX).	[40]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Radixin (RDX).	[41]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Radixin (RDX).	[42]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Radixin (RDX).	[44]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 increases the expression of Radixin (RDX).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Radixin (RDX).	[46]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Radixin (RDX).	[43]

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 increases the methylation of Radixin (RDX).	[45]

References

• [1] 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.
• [2] Radixin knockdown by RNA interference suppresses human glioblastoma cell growth in vitro and in vivo.Asian Pac J Cancer Prev. 2014;15(22):9805-12. doi: 10.7314/apjcp.2014.15.22.9805.
• [3] Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer cell xenograft model, tissue microarray, and gene network analysis.Int J Oncol. 2017 Jul;51(1):204-212. doi: 10.3892/ijo.2017.3993. Epub 2017 May 11.
• [4] Decreased radixin function for ATP-binding cassette transporters in liver in adjuvant-induced arthritis rats.J Pharm Sci. 2014 Dec;103(12):4058-4065. doi: 10.1002/jps.24210. Epub 2014 Oct 20.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Identification of Ezrin-Radixin-Moesin proteins as novel regulators of pathogenic B-cell receptor signaling and tumor growth in diffuse large B-cell lymphoma.Leukemia. 2015 Sep;29(9):1857-67. doi: 10.1038/leu.2015.86. Epub 2015 Mar 24.
• [7] Silencing of phosphoinositide-specific phospholipase C remodulates the expression of the phosphoinositide signal transduction pathway in human osteosarcoma cell lines.Anticancer Res. 2014 Aug;34(8):4069-75.
• [8] Radixin knockdown improves the accumulation and efficiency of methotrexate in tumor cells.Oncol Rep. 2019 Jul;42(1):283-290. doi: 10.3892/or.2019.7162. Epub 2019 May 15.
• [9] Changes in Radixin Expression and Interaction with Efflux Transporters in the Liver of Adjuvant-Induced Arthritic Rats.Inflammation. 2020 Feb;43(1):85-94. doi: 10.1007/s10753-019-01097-9.
• [10] MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas.J Neurooncol. 2013 Nov;115(2):143-51. doi: 10.1007/s11060-013-1211-6. Epub 2013 Aug 3.
• [11] ZINC4085554 inhibits cancer cell adhesion by interfering with the interaction of Akt1 and FAK.Oncol Lett. 2019 Jun;17(6):5251-5260. doi: 10.3892/ol.2019.10192. Epub 2019 Mar 27.
• [12] Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus. Hum Mutat. 2007 May;28(5):417-23. doi: 10.1002/humu.20469.
• [13] Evaluation of associations between single nucleotide polymorphisms in the FRMD3 and CARS genes and diabetic nephropathy in a Kuwaiti population.Genet Mol Res. 2016 Jan 29;15(1). doi: 10.4238/gmr.15017619.
• [14] Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia.J Cell Biol. 2004 Aug 16;166(4):559-70. doi: 10.1083/jcb.200402007.
• [15] Knockdown of Radixin Suppresses Gastric Cancer Metastasis In Vitro by Up-Regulation of E-Cadherin via NF-B/Snail Pathway.Cell Physiol Biochem. 2016;39(6):2509-2521. doi: 10.1159/000452518. Epub 2016 Nov 14.
• [16] Brcal Defective Breast Cancer Cells Induce in vitro Transformation of Cancer Associated Fibroblasts (CAFs) to Metastasis Associated Fibroblasts (MAF).Sci Rep. 2018 Sep 17;8(1):13903. doi: 10.1038/s41598-018-32370-w.
• [17] Misregulation of membrane trafficking processes in human nonalcoholic steatohepatitis.J Biochem Mol Toxicol. 2018 Mar;32(3):e22035. doi: 10.1002/jbt.22035. Epub 2018 Jan 17.
• [18] Knockdown of radixin by RNA interference suppresses the growth of human pancreatic cancer cells in vitro and in vivo.Asian Pac J Cancer Prev. 2012;13(3):753-9. doi: 10.7314/apjcp.2012.13.3.753.
• [19] Proteomic profiling in pancreatic cancer with and without lymph node metastasis.Int J Cancer. 2009 Apr 1;124(7):1614-21. doi: 10.1002/ijc.24163.
• [20] Bioinformatics Analysis Reveals the Altered Gene Expression of Patients with Postmenopausal Osteoporosis Using Liuweidihuang Pills Treatment.Biomed Res Int. 2019 Jan 27;2019:1907906. doi: 10.1155/2019/1907906. eCollection 2019.
• [21] CREB5 computational regulation network construction and analysis between frontal cortex of HIV encephalitis (HIVE) and HIVE-control patients.Cell Biochem Biophys. 2011 Jul;60(3):199-207. doi: 10.1007/s12013-010-9140-x.
• [22] Mutational analysis of the DAL-1/4.1B tumour-suppressor gene locus in meningiomas.Int J Mol Med. 2005 Oct;16(4):771-4.
• [23] Universal absence of merlin, but not other ERM family members, in schwannomas.Am J Pathol. 1997 Dec;151(6):1649-54.
• [24] Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.BMC Med Genomics. 2018 Jul 9;11(1):58. doi: 10.1186/s12920-018-0375-5.
• [25] Genetic Hearing Loss Overview. 1999 Feb 14 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [26] Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis.J Hepatol. 2015 Dec;63(6):1440-8. doi: 10.1016/j.jhep.2015.07.016. Epub 2015 Jul 23.
• [27] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [28] Neurofibromatosis type 2 and von Hippel-Lindau disease: from gene cloning to function.Glia. 1995 Nov;15(3):297-307. doi: 10.1002/glia.440150310.
• [29] Altered expression of the ERM proteins in lung adenocarcinoma.Lab Invest. 2000 Nov;80(11):1643-50. doi: 10.1038/labinvest.3780174.
• [30] VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation.Oncogene. 2008 Jul 3;27(29):4056-64. doi: 10.1038/onc.2008.44. Epub 2008 Mar 10.
• [31] Changes in the expression and localization of hepatocellular transporters and radixin in primary biliary cirrhosis.J Hepatol. 2003 Nov;39(5):693-702. doi: 10.1016/s0168-8278(03)00410-0.
• [32] Screening biomarkers of prostate cancer by integrating microRNA and mRNA microarrays.Genet Test Mol Biomarkers. 2013 Nov;17(11):807-13. doi: 10.1089/gtmb.2013.0226. Epub 2013 Aug 28.
• [33] 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.
• [34] 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.
• [35] Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples. Data Brief. 2016 Mar 26;7:1052-1057. doi: 10.1016/j.dib.2016.03.069. eCollection 2016 Jun.
• [36] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [37] 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.
• [38] 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.
• [39] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [40] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [41] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [42] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [43] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [44] 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.
• [45] 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.
• [46] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [47] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.