Details of Drug Off-Target (DOT)

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

DOT Name Ras-related protein Rab-23 (RAB23)
Gene Name RAB23
Related Disease
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Gastric neoplasm ( )
RAB23-related Carpenter syndrome ( )
Astrocytoma ( )
Ciliopathy ( )
Colorectal carcinoma ( )
Ductal carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Gastrointestinal stromal tumour ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hereditary hemochromatosis ( )
Lung cancer ( )
Lung carcinoma ( )
Matthew-Wood syndrome ( )
Metastatic malignant neoplasm ( )
Neural tube defect ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Sarcoidosis ( )
Skin neoplasm ( )
Basal cell nevus syndrome ( )
Clear cell renal carcinoma ( )
Gastric cancer ( )
Renal cell carcinoma ( )
Stomach cancer ( )
Carpenter syndrome ( )
Intellectual disability ( )
Bone osteosarcoma ( )
Cutaneous squamous cell carcinoma ( )
Osteosarcoma ( )
Squamous cell carcinoma ( )
Streptococcus infection ( )
Thyroid gland follicular carcinoma ( )
Thyroid gland papillary carcinoma ( )
UniProt ID
RAB23_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00071
Sequence
MLEEDMEVAIKMVVVGNGAVGKSSMIQRYCKGIFTKDYKKTIGVDFLERQIQVNDEDVRL
MLWDTAGQEEFDAITKAYYRGAQACVLVFSTTDRESFEAVSSWREKVVAEVGDIPTVLVQ
NKIDLLDDSCIKNEEAEALAKRLKLRFYRTSVKEDLNVNEVFKYLAEKYLQKLKQQIAED
PELTHSSSNKIGVFNTSGGSHSGQNSGTLNGGDVINLRPNKQRTKKNRNPFSSCSIP
Function
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Together with SUFU, prevents nuclear import of GLI1, and thereby inhibits GLI1 transcription factor activity. Regulates GLI1 in differentiating chondrocytes. Likewise, regulates GLI3 proteolytic processing and modulates GLI2 and GLI3 transcription factor activity. Plays a role in autophagic vacuole assembly, and mediates defense against pathogens, such as S.aureus, by promoting their capture by autophagosomes that then merge with lysosomes.
Reactome Pathway
RAB geranylgeranylation (R-HSA-8873719 )

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Altered Expression [1]
Breast cancer DIS7DPX1 Definitive Biomarker [2]
Breast carcinoma DIS2UE88 Definitive Biomarker [2]
Gastric neoplasm DISOKN4Y Definitive Biomarker [3]
RAB23-related Carpenter syndrome DISR9P09 Definitive Autosomal recessive [4]
Astrocytoma DISL3V18 Strong Biomarker [5]
Ciliopathy DIS10G4I Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [7]
Ductal carcinoma DIS15EA5 Strong Altered Expression [8]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [9]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [1]
Gastrointestinal stromal tumour DIS6TJYS Strong Biomarker [10]
Glioma DIS5RPEH Strong Altered Expression [11]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [12]
Hereditary hemochromatosis DISVG5MT Strong Biomarker [6]
Lung cancer DISCM4YA Strong Altered Expression [13]
Lung carcinoma DISTR26C Strong Altered Expression [13]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [8]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [8]
Neural tube defect DIS5J95E Strong Altered Expression [14]
Ovarian cancer DISZJHAP Strong Altered Expression [9]
Ovarian neoplasm DISEAFTY Strong Altered Expression [9]
Pancreatic cancer DISJC981 Strong Biomarker [8]
Prostate cancer DISF190Y Strong Altered Expression [15]
Prostate carcinoma DISMJPLE Strong Altered Expression [15]
Sarcoidosis DISE5B8Z Strong Biomarker [16]
Skin neoplasm DIS16DDV Strong Altered Expression [14]
Basal cell nevus syndrome DIST8BC2 moderate Biomarker [17]
Clear cell renal carcinoma DISBXRFJ moderate Altered Expression [18]
Gastric cancer DISXGOUK moderate Biomarker [19]
Renal cell carcinoma DISQZ2X8 moderate Altered Expression [18]
Stomach cancer DISKIJSX moderate Biomarker [19]
Carpenter syndrome DISU690E Supportive Autosomal recessive [20]
Intellectual disability DISMBNXP Disputed Genetic Variation [21]
Bone osteosarcoma DIST1004 Limited Altered Expression [22]
Cutaneous squamous cell carcinoma DIS3LXUG Limited Biomarker [23]
Osteosarcoma DISLQ7E2 Limited Altered Expression [22]
Squamous cell carcinoma DISQVIFL Limited Biomarker [23]
Streptococcus infection DIS04U9T Limited Biomarker [24]
Thyroid gland follicular carcinoma DISFK2QT Limited Altered Expression [25]
Thyroid gland papillary carcinoma DIS48YMM Limited Genetic Variation [25]
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⏷ Show the Full List of 41 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
18 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Ras-related protein Rab-23 (RAB23). [26]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Ras-related protein Rab-23 (RAB23). [27]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Ras-related protein Rab-23 (RAB23). [28]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Ras-related protein Rab-23 (RAB23). [29]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Ras-related protein Rab-23 (RAB23). [30]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Ras-related protein Rab-23 (RAB23). [31]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Ras-related protein Rab-23 (RAB23). [32]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Ras-related protein Rab-23 (RAB23). [33]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Ras-related protein Rab-23 (RAB23). [33]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Ras-related protein Rab-23 (RAB23). [34]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Ras-related protein Rab-23 (RAB23). [35]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Ras-related protein Rab-23 (RAB23). [36]
Liothyronine DM6IR3P Approved Liothyronine decreases the expression of Ras-related protein Rab-23 (RAB23). [37]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Ras-related protein Rab-23 (RAB23). [38]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Ras-related protein Rab-23 (RAB23). [39]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Ras-related protein Rab-23 (RAB23). [40]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Ras-related protein Rab-23 (RAB23). [41]
Manganese DMKT129 Investigative Manganese decreases the expression of Ras-related protein Rab-23 (RAB23). [42]
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⏷ Show the Full List of 18 Drug(s)

References

1 RAB23, regulated by miR-92b, promotes the progression of esophageal squamous cell carcinoma.Gene. 2016 Dec 20;595(1):31-38. doi: 10.1016/j.gene.2016.09.028. Epub 2016 Sep 19.
2 Effect of Rab23 on the proliferation and apoptosis in breast cancer.Oncol Rep. 2015 Oct;34(4):1835-44. doi: 10.3892/or.2015.4152. Epub 2015 Jul 24.
3 Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer.Cancer Res. 2008 Jun 15;68(12):4623-30. doi: 10.1158/0008-5472.CAN-07-5870.
4 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.
5 Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1.Tumour Biol. 2016 Aug;37(8):11049-55. doi: 10.1007/s13277-016-4949-6. Epub 2016 Feb 20.
6 Small GTPases in hedgehog signalling: emerging insights into the disease mechanisms of Rab23-mediated and Arl13b-mediated ciliopathies.Curr Opin Genet Dev. 2019 Jun;56:61-68. doi: 10.1016/j.gde.2019.07.009. Epub 2019 Aug 27.
7 Rab23 contributes to the progression of colorectal cancer via protein kinase B and extracellular signal-regulated kinase signaling pathways.Oncol Lett. 2019 Aug;18(2):1793-1799. doi: 10.3892/ol.2019.10491. Epub 2019 Jun 18.
8 Inactivation of Rab23 inhibits the invasion and motility of pancreatic duct adenocarcinoma.Genet Mol Res. 2015 Mar 30;14(1):2707-15. doi: 10.4238/2015.March.30.31.
9 Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway.Oncol Lett. 2018 Apr;15(4):5155-5160. doi: 10.3892/ol.2018.7949. Epub 2018 Feb 5.
10 Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. Oncotarget. 2016 Nov 29;7(48):78226-78241. doi: 10.18632/oncotarget.12909.
11 miR-200b as a prognostic factor targets multiple members of RAB family in glioma.Med Oncol. 2014 Mar;31(3):859. doi: 10.1007/s12032-014-0859-x. Epub 2014 Jan 30.
12 lncRNA OSER1-AS1 acts as a ceRNA to promote tumorigenesis in hepatocellular carcinoma by regulating miR-372-3p/Rab23 axis.Biochem Biophys Res Commun. 2020 Jan 1;521(1):196-203. doi: 10.1016/j.bbrc.2019.10.105. Epub 2019 Oct 18.
13 Sublocalization of Rab23, a mediator of Sonic hedgehog signaling pathway, in hepatocellular carcinoma cell lines.Mol Med Rep. 2012 Dec;6(6):1276-80. doi: 10.3892/mmr.2012.1094. Epub 2012 Sep 20.
14 Rab23's genetic structure, function and related diseases: a review.Biosci Rep. 2017 Mar 2;37(2):BSR20160410. doi: 10.1042/BSR20160410. Print 2017 Apr 30.
15 miR-338-3p targets RAB23 and suppresses tumorigenicity of prostate cancer cells.Am J Cancer Res. 2018 Dec 1;8(12):2564-2574. eCollection 2018.
16 A genome-wide association study reveals evidence of association with sarcoidosis at 6p12.1.Eur Respir J. 2011 Nov;38(5):1127-35. doi: 10.1183/09031936.00001711. Epub 2011 May 3.
17 Bifid ribs and unusual vertebral anomalies diagnosed in an anatomical specimen. Gorlin syndrome?.Am J Med Genet A. 2006 Oct 1;140(19):2135-8. doi: 10.1002/ajmg.a.31418.
18 miR-384 suppressed renal cell carcinoma cell proliferation and migration through targeting RAB23.J Cell Biochem. 2019 Feb;120(2):1420-1426. doi: 10.1002/jcb.27180. Epub 2018 Nov 2.
19 Upregulation of miR-802 suppresses gastric cancer oncogenicity via targeting RAB23 expression.Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4071-4078.
20 RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. Am J Hum Genet. 2007 Jun;80(6):1162-70. doi: 10.1086/518047. Epub 2007 Apr 18.
21 Rab23 and developmental disorders.Rev Neurosci. 2018 Nov 27;29(8):849-860. doi: 10.1515/revneuro-2017-0110.
22 MicroRNA-16 suppressed the invasion and migration of osteosarcoma by directly inhibiting RAB23.Eur Rev Med Pharmacol Sci. 2018 May;22(9):2598-2605. doi: 10.26355/eurrev_201805_14953.
23 Rab23 promotes squamous cell carcinoma cell migration and invasion via integrin 1/Rac1 pathway.Oncotarget. 2016 Feb 2;7(5):5342-52. doi: 10.18632/oncotarget.6701.
24 The small GTPases Rab9A and Rab23 function at distinct steps in autophagy during Group A Streptococcus infection.Cell Microbiol. 2012 Aug;14(8):1149-65. doi: 10.1111/j.1462-5822.2012.01792.x. Epub 2012 Apr 17.
25 A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples.Mod Pathol. 2007 Oct;20(10):1095-102. doi: 10.1038/modpathol.3800943. Epub 2007 Jul 27.
26 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
27 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
28 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.
29 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
30 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.
31 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.
32 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
33 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
34 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
35 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
36 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
37 Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
38 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
39 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.
40 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
41 Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
42 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.