Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB19LEQ)

DOT Name Protein odd-skipped-related 1 (OSR1)
Gene Name OSR1
Related Disease
Carcinoma of esophagus ( )
Esophageal cancer ( )
Generalized anxiety disorder ( )
Neoplasm of esophagus ( )
Advanced cancer ( )
Alagille syndrome ( )
Anxiety disorder ( )
Bone cancer ( )
Bone osteosarcoma ( )
Clear cell renal carcinoma ( )
Conduct disorder ( )
Cowden disease ( )
Depression ( )
Disruptive behavior disorder ( )
Gastric cancer ( )
High blood pressure ( )
Huntington disease ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Mental disorder ( )
Mitochondrial DNA depletion syndrome 4a ( )
Mood disorder ( )
Polycystic kidney disease ( )
Prostate neoplasm ( )
Renal cell carcinoma ( )
Stomach cancer ( )
Vesicoureteral reflux ( )
Gordon syndrome ( )
Hepatocellular carcinoma ( )
Hyperinsulinemia ( )
Squamous cell carcinoma ( )
Aortic aneurysm ( )
Melanoma ( )
Non-small-cell lung cancer ( )
Anxiety ( )
Atrial septal defect ( )
Childhood kidney Wilms tumor ( )
Neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Wilms tumor ( )
UniProt ID
OSR1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00096
Sequence
MGSKTLPAPVPIHPSLQLTNYSFLQAVNGLPTVPSDHLPNLYGFSALHAVHLHQWTLGYP
AMHLPRSSFSKVPGTVSSLVDARFQLPAFPWFPHVIQPKPEITAGGSVPALKTKPRFDFA
NLALAATQEDPAKLGRGEGPGSPAGGLGALLDVTKLSPEKKPTRGRLPSKTKKEFVCKFC
GRHFTKSYNLLIHERTHTDERPYTCDICHKAFRRQDHLRDHRYIHSKEKPFKCQECGKGF
CQSRTLAVHKTLHSQVKELKTSKIKC
Function Transcription factor that plays a role in the regulation of embryonic heart and urogenital development.
Tissue Specificity Expressed in adult colon, small intestine, prostate, testis, and fetal lung.
Reactome Pathway
Formation of intermediate mesoderm (R-HSA-9761174 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of esophagus DISS6G4D Definitive Altered Expression [1]
Esophageal cancer DISGB2VN Definitive Altered Expression [1]
Generalized anxiety disorder DISPSQCW Definitive Biomarker [2]
Neoplasm of esophagus DISOLKAQ Definitive Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alagille syndrome DIS9DPU8 Strong Biomarker [4]
Anxiety disorder DISBI2BT Strong Genetic Variation [5]
Bone cancer DIS38NA0 Strong Biomarker [6]
Bone osteosarcoma DIST1004 Strong Biomarker [6]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [7]
Conduct disorder DISOLUZ1 Strong Biomarker [8]
Cowden disease DISMYKCE Strong Biomarker [8]
Depression DIS3XJ69 Strong Biomarker [9]
Disruptive behavior disorder DIS5ACCI Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Biomarker [11]
High blood pressure DISY2OHH Strong Biomarker [12]
Huntington disease DISQPLA4 Strong Altered Expression [13]
Lung adenocarcinoma DISD51WR Strong Biomarker [14]
Lung cancer DISCM4YA Strong Altered Expression [15]
Lung carcinoma DISTR26C Strong Biomarker [15]
Mental disorder DIS3J5R8 Strong Biomarker [16]
Mitochondrial DNA depletion syndrome 4a DISU4RVU Strong Biomarker [4]
Mood disorder DISLVMWO Strong Biomarker [2]
Polycystic kidney disease DISWS3UY Strong Biomarker [12]
Prostate neoplasm DISHDKGQ Strong Altered Expression [17]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [7]
Stomach cancer DISKIJSX Strong Biomarker [11]
Vesicoureteral reflux DISUL6SA Strong Biomarker [18]
Gordon syndrome DISVMP0Y moderate Biomarker [19]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [20]
Hyperinsulinemia DISIDWT6 moderate Biomarker [21]
Squamous cell carcinoma DISQVIFL moderate Biomarker [22]
Aortic aneurysm DISQ5KRA Disputed Biomarker [23]
Melanoma DIS1RRCY Disputed Biomarker [23]
Non-small-cell lung cancer DIS5Y6R9 Disputed Biomarker [23]
Anxiety DISIJDBA Limited Genetic Variation [5]
Atrial septal defect DISJT76B Limited Biomarker [24]
Childhood kidney Wilms tumor DIS0NMK3 Limited Altered Expression [25]
Neoplasm DISZKGEW Limited Biomarker [23]
Prostate cancer DISF190Y Limited Genetic Variation [26]
Prostate carcinoma DISMJPLE Limited Genetic Variation [26]
Wilms tumor DISB6T16 Limited Altered Expression [25]
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⏷ Show the Full List of 42 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Protein odd-skipped-related 1 (OSR1). [27]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Protein odd-skipped-related 1 (OSR1). [29]
Triclosan DMZUR4N Approved Triclosan increases the expression of Protein odd-skipped-related 1 (OSR1). [30]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Protein odd-skipped-related 1 (OSR1). [31]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Protein odd-skipped-related 1 (OSR1). [32]
Aspirin DM672AH Approved Aspirin increases the expression of Protein odd-skipped-related 1 (OSR1). [33]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Protein odd-skipped-related 1 (OSR1). [34]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Protein odd-skipped-related 1 (OSR1). [36]
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⏷ Show the Full List of 8 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Protein odd-skipped-related 1 (OSR1). [28]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Protein odd-skipped-related 1 (OSR1). [35]
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References

1 Molecular cloning and characterization of OSR1 on human chromosome 2p24.Int J Mol Med. 2002 Aug;10(2):221-5.
2 External validation of a bifactor model of oppositional defiant disorder.Mol Psychiatry. 2021 Feb;26(2):682-693. doi: 10.1038/s41380-018-0294-z. Epub 2018 Dec 11.
3 Ascorbic acid metabolism and functions: A comparison of plants and mammals.Free Radic Biol Med. 2018 Jul;122:116-129. doi: 10.1016/j.freeradbiomed.2018.03.033. Epub 2018 Mar 20.
4 Child and adolescent traumatic brain injury: correlates of disruptive behaviour disorders.Brain Inj. 1998 Jan;12(1):41-52. doi: 10.1080/026990598122845.
5 Examining the relationships between error-related brain activity (the ERN) and anxiety disorders versus externalizing disorders in young children: Focusing on cognitive control, fear, and shyness.Compr Psychiatry. 2018 Nov;87:112-119. doi: 10.1016/j.comppsych.2018.09.009. Epub 2018 Oct 7.
6 Suppression of WNK1-SPAK/OSR1 Attenuates Bone Cancer Pain by Regulating NKCC1 and KCC2.J Pain. 2019 Dec;20(12):1416-1428. doi: 10.1016/j.jpain.2019.05.005. Epub 2019 May 11.
7 Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-B pathway.Eur J Pharmacol. 2018 Nov 15;839:33-39. doi: 10.1016/j.ejphar.2018.09.020. Epub 2018 Sep 19.
8 The role of effortful control in the development of ADHD, ODD, and CD symptoms.J Pers Soc Psychol. 2020 Jun;118(6):1226-1246. doi: 10.1037/pspp0000243. Epub 2019 Mar 28.
9 Genetic Overlap Between Schizophrenia and Developmental Psychopathology: Longitudinal and Multivariate Polygenic Risk Prediction of Common Psychiatric Traits During Development.Schizophr Bull. 2017 Oct 21;43(6):1197-1207. doi: 10.1093/schbul/sbx031.
10 Oppositional Defiant Disorder Is Better Conceptualized as a Disorder of Emotional Regulation.J Atten Disord. 2017 Mar;21(5):381-389. doi: 10.1177/1087054713520221. Epub 2016 Jul 28.
11 Odd-skipped related 1 is a novel tumour suppressor gene and a potential prognostic biomarker in gastric cancer.J Pathol. 2014 Nov;234(3):302-15. doi: 10.1002/path.4391. Epub 2014 Aug 28.
12 Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.Ther Apher Dial. 2020 Feb;24(1):64-71. doi: 10.1111/1744-9987.12814. Epub 2019 Jul 4.
13 Transcriptomics of maternal and fetal membranes can discriminate between gestational-age matched preterm neonates with and without cognitive impairment diagnosed at 18-24 months.PLoS One. 2015 Mar 30;10(3):e0118573. doi: 10.1371/journal.pone.0118573. eCollection 2015.
14 Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma.Sci Rep. 2016 Oct 26;6:35807. doi: 10.1038/srep35807.
15 Odd-skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and -catenin.Cancer Sci. 2018 Jun;109(6):1799-1810. doi: 10.1111/cas.13614. Epub 2018 May 23.
16 Do Individual Differences in Early Affective and Cognitive Self-Regulation Predict Developmental Change in ADHD Symptoms From Preschool to Adolescence?.J Atten Disord. 2017 Feb 1;23(13):1656-1666. doi: 10.1177/1087054717693372. Print 2019 Nov 1.
17 Conditional expression of the androgen receptor induces oncogenic transformation of the mouse prostate.J Biol Chem. 2011 Sep 23;286(38):33478-88. doi: 10.1074/jbc.M111.269894. Epub 2011 Jul 27.
18 Heterozygous loss-of-function mutation in Odd-skipped related 1 (Osr1) is associated with vesicoureteric reflux, duplex systems, and hydronephrosis.Am J Physiol Renal Physiol. 2017 Nov 1;313(5):F1106-F1115. doi: 10.1152/ajprenal.00107.2017. Epub 2017 Jul 19.
19 Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1.Biochem J. 2006 Jul 1;397(1):223-31. doi: 10.1042/BJ20060220.
20 Discovery of NKCC1 as a potential therapeutic target to inhibit hepatocellular carcinoma cell growth and metastasis.Oncotarget. 2017 Aug 12;8(39):66328-66342. doi: 10.18632/oncotarget.20240. eCollection 2017 Sep 12.
21 Regulation of with-no-lysine kinase signaling by Kelch-like proteins.Biol Cell. 2014 Feb;106(2):45-56. doi: 10.1111/boc.201300069. Epub 2014 Jan 10.
22 DNA methylation biomarkers for lung cancer.Tumour Biol. 2012 Apr;33(2):287-96. doi: 10.1007/s13277-011-0282-2. Epub 2011 Dec 6.
23 Trial watch: Peptide-based vaccines in anticancer therapy.Oncoimmunology. 2018 Sep 6;7(12):e1511506. doi: 10.1080/2162402X.2018.1511506. eCollection 2018.
24 Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD.Eur Child Adolesc Psychiatry. 2018 Jul;27(7):899-908. doi: 10.1007/s00787-017-1089-5. Epub 2017 Dec 9.
25 Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin.Genes Chromosomes Cancer. 2014 May;53(5):381-91. doi: 10.1002/gcc.22149. Epub 2014 Feb 1.
26 Combining Optical Reporter Proteins with Different Half-lives to Detect Temporal Evolution of Hypoxia and Reoxygenation in Tumors.Neoplasia. 2015 Dec;17(12):871-881. doi: 10.1016/j.neo.2015.11.007.
27 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.
28 Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
29 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
30 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
31 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
32 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
33 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
34 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
35 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.
36 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.