Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCX1SMK)

DOT Name Reticulon-1 (RTN1)
Synonyms Neuroendocrine-specific protein
Gene Name RTN1
Related Disease
Nephropathy ( )
Adenocarcinoma ( )
Advanced cancer ( )
Carcinoid tumor ( )
Chronic kidney disease ( )
facioscapulohumeral muscular dystrophy ( )
Frontometaphyseal dysplasia 1 ( )
Hereditary spastic paraplegia ( )
Lung carcinoma ( )
Lung neoplasm ( )
Major depressive disorder ( )
Myocardial ischemia ( )
Parkinson disease ( )
Renal fibrosis ( )
Sarcoidosis ( )
Small-cell lung cancer ( )
Chronic renal failure ( )
Encephalitis ( )
End-stage renal disease ( )
Gastrointestinal stromal tumour ( )
Non-insulin dependent diabetes ( )
Breast cancer ( )
Breast carcinoma ( )
Estrogen resistance syndrome ( )
Colorectal cancer ( )
Colorectal carcinoma ( )
Hepatitis C virus infection ( )
Schizophrenia ( )
Stroke ( )
UniProt ID
RTN1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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Pfam ID
PF02453
Sequence
MAAPGDPQDELLPLAGPGSQWLRHRGEGENEAVTPKGATPAPQAGEPSPGLGARAREAAS
REAGSGPARQSPVAMETASTGVAGVSSAMDHTFSTTSKDGEGSCYTSLISDICYPPQEDS
TYFTGILQKENGHVTISESPEELGTPGPSLPDVPGIESRGLFSSDSGIEMTPAESTEVNK
ILADPLDQMKAEAYKYIDITRPEEVKHQEQHHPELEDKDLDFKNKDTDISIKPEGVREPD
KPAPVEGKIIKDHLLEESTFAPYIDDLSEEQRRAPQITTPVKITLTEIEPSVETTTQEKT
PEKQDICLKPSPDTVPTVTVSEPEDDSPGSITPPSSGTEPSAAESQGKGSISEDELITAI
KEAKGLSYETAENPRPVGQLADRPEVKARSGPPTIPSPLDHEASSAESGDSEIELVSEDP
MAAEDALPSGYVSFGHVGGPPPSPASPSIQYSILREEREAELDSELIIESCDASSASEES
PKREQDSPPMKPSALDAIREETGVRAEERAPSRRGLAEPGSFLDYPSTEPQPGPELPPGD
GALEPETPMLPRKPEEDSSSNQSPAATKGPGPLGPGAPPPLLFLNKQKAIDLLYWRDIKQ
TGIVFGSFLLLLFSLTQFSVVSVVAYLALAALSATISFRIYKSVLQAVQKTDEGHPFKAY
LELEITLSQEQIQKYTDCLQFYVNSTLKELRRLFLVQDLVDSLKFAVLMWLLTYVGALFN
GLTLLLMAVVSMFTLPVVYVKHQAQIDQYLGLVRTHINAVVAKIQAKIPGAKRHAE
Function Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.
Tissue Specificity Expressed in neural and neuroendocrine tissues and cell cultures derived therefrom. Expression of isoform RTN1-C is strongly correlated with neuronal differentiation.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Nephropathy DISXWP4P Definitive Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Carcinoid tumor DISMNRDC Strong Biomarker [4]
Chronic kidney disease DISW82R7 Strong Altered Expression [5]
facioscapulohumeral muscular dystrophy DISSE0H0 Strong Biomarker [6]
Frontometaphyseal dysplasia 1 DIS2MB3L Strong Biomarker [6]
Hereditary spastic paraplegia DISGZQV1 Strong Biomarker [7]
Lung carcinoma DISTR26C Strong Altered Expression [4]
Lung neoplasm DISVARNB Strong Altered Expression [4]
Major depressive disorder DIS4CL3X Strong Genetic Variation [8]
Myocardial ischemia DISFTVXF Strong Biomarker [9]
Parkinson disease DISQVHKL Strong Biomarker [10]
Renal fibrosis DISMHI3I Strong Biomarker [1]
Sarcoidosis DISE5B8Z Strong Biomarker [11]
Small-cell lung cancer DISK3LZD Strong Biomarker [4]
Chronic renal failure DISGG7K6 moderate Genetic Variation [12]
Encephalitis DISLD1RL moderate Biomarker [13]
End-stage renal disease DISXA7GG moderate Genetic Variation [12]
Gastrointestinal stromal tumour DIS6TJYS moderate Biomarker [14]
Non-insulin dependent diabetes DISK1O5Z moderate Genetic Variation [12]
Breast cancer DIS7DPX1 Disputed Biomarker [15]
Breast carcinoma DIS2UE88 Disputed Biomarker [15]
Estrogen resistance syndrome DIS2SYXC Disputed Biomarker [15]
Colorectal cancer DISNH7P9 Limited Biomarker [16]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [16]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [17]
Schizophrenia DISSRV2N Limited Genetic Variation [18]
Stroke DISX6UHX Limited Biomarker [19]
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⏷ Show the Full List of 29 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Reticulon-1 (RTN1). [20]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Reticulon-1 (RTN1). [25]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Reticulon-1 (RTN1). [30]
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15 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 Reticulon-1 (RTN1). [21]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Reticulon-1 (RTN1). [22]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Reticulon-1 (RTN1). [23]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Reticulon-1 (RTN1). [24]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Reticulon-1 (RTN1). [26]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Reticulon-1 (RTN1). [26]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Reticulon-1 (RTN1). [27]
Cytarabine DMZD5QR Approved Cytarabine increases the expression of Reticulon-1 (RTN1). [28]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of Reticulon-1 (RTN1). [29]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Reticulon-1 (RTN1). [26]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Reticulon-1 (RTN1). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Reticulon-1 (RTN1). [31]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Reticulon-1 (RTN1). [32]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Reticulon-1 (RTN1). [33]
Lithium chloride DMHYLQ2 Investigative Lithium chloride decreases the expression of Reticulon-1 (RTN1). [34]
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⏷ Show the Full List of 15 Drug(s)

References

1 Knockdown of RTN1A attenuates ER stress and kidney injury in albumin overload-induced nephropathy.Am J Physiol Renal Physiol. 2016 Mar 1;310(5):F409-15. doi: 10.1152/ajprenal.00485.2015. Epub 2016 Jan 6.
2 A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1.Hum Genet. 2015 Nov;134(11-12):1249-1262. doi: 10.1007/s00439-015-1598-6. Epub 2015 Sep 24.
3 Breast cancer screening: Impact on care pathways.Cancer Med. 2019 Jul;8(8):4070-4078. doi: 10.1002/cam4.2283. Epub 2019 Jun 6.
4 NSP-encoded reticulons are neuroendocrine markers of a novel category in human lung cancer diagnosis.Cancer Res. 1994 Sep 1;54(17):4769-76.
5 RTN1 mediates progression of kidney disease by inducing ER stress.Nat Commun. 2015 Jul 31;6:7841. doi: 10.1038/ncomms8841.
6 Development and validation of a foot-and-mouth disease virus SAT serotype-specific 3ABC assay to differentiate infected from vaccinated animals.J Virol Methods. 2018 May;255:44-51. doi: 10.1016/j.jviromet.2018.02.006. Epub 2018 Feb 8.
7 Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein.Neurogenetics. 2006 May;7(2):93-103. doi: 10.1007/s10048-006-0034-4. Epub 2006 Apr 7.
8 Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
9 Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
10 Downregulation of RTN1-C attenuates MPP(+)-induced neuronal injury through inhibition of mGluR5 pathway in SN4741 cells.Brain Res Bull. 2019 Mar;146:1-6. doi: 10.1016/j.brainresbull.2018.11.026. Epub 2018 Dec 3.
11 Quantifying the relationship between symptoms at presentation and the prognosis of sarcoidosis.Respir Med. 2019 Jun;152:14-19. doi: 10.1016/j.rmed.2019.03.012. Epub 2019 Mar 23.
12 Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease.Am J Nephrol. 2015;42(4):259-64. doi: 10.1159/000441199. Epub 2015 Oct 24.
13 Encephalitis is mediated by ROP18 of Toxoplasma gondii, a severe pathogen in AIDS patients.Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):E5344-E5352. doi: 10.1073/pnas.1801118115. Epub 2018 May 21.
14 A molecular portrait of gastrointestinal stromal tumors: an integrative analysis of gene expression profiling and high-resolution genomic copy number.Lab Invest. 2010 Sep;90(9):1285-94. doi: 10.1038/labinvest.2010.110. Epub 2010 Jun 14.
15 AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology.J Cell Physiol. 2007 Sep;212(3):655-65. doi: 10.1002/jcp.21059.
16 Meat, starch and non-starch polysaccharides, are epidemiological and experimental findings consistent with acquired genetic alterations in sporadic colorectal cancer?.Cancer Lett. 1997 Mar 19;114(1-2):25-34. doi: 10.1016/s0304-3835(97)04618-1.
17 High risk injecting behaviour among people who inject pharmaceutical opioids in Australia.Int J Drug Policy. 2017 Apr;42:1-6. doi: 10.1016/j.drugpo.2016.12.004. Epub 2017 Jan 16.
18 Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
19 A novel free radical scavenger, NSP-116, ameliorated the brain injury in both ischemic and hemorrhagic stroke models.J Pharmacol Sci. 2019 Nov;141(3):119-126. doi: 10.1016/j.jphs.2019.09.012. Epub 2019 Oct 15.
20 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
21 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.
22 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
23 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
24 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.
25 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
26 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
27 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
28 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.
29 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
30 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.
31 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
32 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
33 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
34 Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.