Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB0IWLW)

DOT Name Transcription factor COE3 (EBF3)
Synonyms Early B-cell factor 3; EBF-3; Olf-1/EBF-like 2; O/E-2; OE-2
Gene Name EBF3
Related Disease
Hypotonia, ataxia, and delayed development syndrome ( )
Parkinson disease ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Brain neoplasm ( )
Cerebellar ataxia ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Intellectual disability ( )
Medulloblastoma ( )
Osteoarthritis ( )
Pulmonary fibrosis ( )
Rheumatoid arthritis ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
High blood pressure ( )
Apraxia ( )
Isolated Pierre-Robin syndrome ( )
Melanoma ( )
Metastatic melanoma ( )
Movement disorder ( )
UniProt ID
COE3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3MUJ; 3N50
Pfam ID
PF16422 ; PF16423 ; PF01833
Sequence
MFGIQENIPRGGTTMKEEPLGSGMNPVRSWMHTAGVVDANTAAQSGVGLARAHFEKQPPS
NLRKSNFFHFVLALYDRQGQPVEIERTAFVDFVEKEKEPNNEKTNNGIHYKLQLLYSNGV
RTEQDLYVRLIDSMTKQAIVYEGQDKNPEMCRVLLTHEIMCSRCCDKKSCGNRNETPSDP
VIIDRFFLKFFLKCNQNCLKNAGNPRDMRRFQVVVSTTVNVDGHVLAVSDNMFVHNNSKH
GRRARRLDPSEGTAPSYLENATPCIKAISPSEGWTTGGATVIIIGDNFFDGLQVVFGTML
VWSELITPHAIRVQTPPRHIPGVVEVTLSYKSKQFCKGAPGRFVYTALNEPTIDYGFQRL
QKVIPRHPGDPERLPKEVLLKRAADLVEALYGMPHNNQEIILKRAADIAEALYSVPRNHN
QIPTLGNNPAHTGMMGVNSFSSQLAVNVSETSQANDQVGYSRNTSSVSPRGYVPSSTPQQ
SNYNTVSTSMNGYGSGAMASLGVPGSPGFLNGSSANSPYGIVPSSPTMAASSVTLPSNCS
STHGIFSFSPANVISAVKQKSAFAPVVRPQASPPPSCTSANGNGLQAMSGLVVPPM
Function Transcriptional activator. Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3'.
Tissue Specificity Expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hypotonia, ataxia, and delayed development syndrome DISZTBVI Definitive Autosomal dominant [1]
Parkinson disease DISQVHKL Definitive Biomarker [2]
Acute monocytic leukemia DIS28NEL Strong Posttranslational Modification [3]
Acute myelogenous leukaemia DISCSPTN Strong Posttranslational Modification [3]
Adult glioblastoma DISVP4LU Strong Genetic Variation [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Brain neoplasm DISY3EKS Strong Altered Expression [6]
Cerebellar ataxia DIS9IRAV Strong CausalMutation [7]
Gastric cancer DISXGOUK Strong Biomarker [8]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [3]
Intellectual disability DISMBNXP Strong Altered Expression [9]
Medulloblastoma DISZD2ZL Strong Biomarker [4]
Osteoarthritis DIS05URM Strong Biomarker [10]
Pulmonary fibrosis DISQKVLA Strong Biomarker [11]
Rheumatoid arthritis DISTSB4J Strong Posttranslational Modification [10]
Squamous cell carcinoma DISQVIFL Strong Posttranslational Modification [12]
Stomach cancer DISKIJSX Strong Posttranslational Modification [8]
High blood pressure DISY2OHH moderate Biomarker [13]
Apraxia DISULX63 Limited CausalMutation [7]
Isolated Pierre-Robin syndrome DISVEHG7 Limited CausalMutation [7]
Melanoma DIS1RRCY Limited Altered Expression [14]
Metastatic melanoma DISSL43L Limited Altered Expression [14]
Movement disorder DISOJJ2D Limited Genetic Variation [9]
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⏷ Show the Full List of 24 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 Transcription factor COE3 (EBF3). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Transcription factor COE3 (EBF3). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Transcription factor COE3 (EBF3). [21]
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4 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 Transcription factor COE3 (EBF3). [16]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Transcription factor COE3 (EBF3). [17]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcription factor COE3 (EBF3). [18]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Transcription factor COE3 (EBF3). [19]
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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 Identification of Critical Genes and miRNAs Associated with the Development of Parkinson's Disease.J Mol Neurosci. 2018 Aug;65(4):527-535. doi: 10.1007/s12031-018-1129-8. Epub 2018 Aug 6.
3 Early B-cell factor 3 (EBF3) is a novel tumor suppressor gene with promoter hypermethylation in pediatric acute myeloid leukemia.J Exp Clin Cancer Res. 2015 Jan 22;34(1):4. doi: 10.1186/s13046-014-0118-1.
4 Apples to origins: identifying brain tumor stem cell genes by comparing transcriptomes of normal and cancer stem cells.Cancer Discov. 2012 Jun;2(6):492-4. doi: 10.1158/2159-8290.CD-12-0182.
5 Long Noncoding RNA EBF3-AS Promotes Neuron Apoptosis in Alzheimer's Disease.DNA Cell Biol. 2018 Mar;37(3):220-226. doi: 10.1089/dna.2017.4012. Epub 2018 Jan 3.
6 An EBF3-mediated transcriptional program that induces cell cycle arrest and apoptosis.Cancer Res. 2006 Oct 1;66(19):9445-52. doi: 10.1158/0008-5472.CAN-06-1713.
7 A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3.Am J Hum Genet. 2017 Jan 5;100(1):128-137. doi: 10.1016/j.ajhg.2016.11.018. Epub 2016 Dec 22.
8 Aberrant DNA methylation and tumor suppressive activity of the EBF3 gene in gastric carcinoma.Int J Cancer. 2012 Feb 15;130(4):817-26. doi: 10.1002/ijc.26038. Epub 2011 May 5.
9 Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism.Am J Hum Genet. 2017 Jan 5;100(1):117-127. doi: 10.1016/j.ajhg.2016.11.012. Epub 2016 Dec 22.
10 Hypermethylation of EBF3 and IRX1 genes in synovial fibroblasts of patients with rheumatoid arthritis.Mol Cells. 2013 Apr;35(4):298-304. doi: 10.1007/s10059-013-2302-0. Epub 2013 Feb 26.
11 Associations of Pulmonary Fibrosis with Peripheral Blood Th1/Th2 Cell Imbalance and EBF3 Gene Methylation in Uygur Pigeon Breeder's Lung Patients.Cell Physiol Biochem. 2018;47(3):1141-1151. doi: 10.1159/000490208. Epub 2018 Jun 15.
12 Frequently methylated tumor suppressor genes in head and neck squamous cell carcinoma.Cancer Res. 2008 Jun 15;68(12):4494-9. doi: 10.1158/0008-5472.CAN-07-6509.
13 Identifications of potential therapeutic targets and drugs in angiotensin II-induced hypertension.Medicine (Baltimore). 2017 Nov;96(46):e8501. doi: 10.1097/MD.0000000000008501.
14 Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis.Oncotarget. 2017 Jan 24;8(4):6085-6101. doi: 10.18632/oncotarget.14042.
15 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.
16 Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
17 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.
18 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.
19 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.
20 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.
21 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.