Details of Drug Off-Target (DOT)

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

DOT Name EvC complex member EVC (EVC)
Synonyms DWF-1; Ellis-van Creveld syndrome protein
Gene Name EVC
Related Disease
Acrofacial dysostosis, Weyers type ( )
Ellis-van Creveld syndrome ( )
Wolfram syndrome ( )
Atrial septal defect ( )
Bipolar disorder ( )
Congenital deformities of limbs ( )
Congenital heart disease ( )
Dysplasia ( )
Non-insulin dependent diabetes ( )
Ventricular septal defect ( )
Achondroplasia ( )
UniProt ID
EVC_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MARGGAACKSDARLLLGRDALRPAPALLAPAVLLGAALGLGLGLWLGCRAGRQRTRHQKD
DTQNLLKNLESNAQTPSETGSPSRRRKREVQMSKDKEAVDECEPPSNSNITAFALKAKVI
YPINQKFRPLADGSSNPSLHENLKQAVLPHQPVEASPSSSLGSLSQGEKDDCSSSSSVHS
ATSDDRFLSRTFLRVNAFPEVLACESVDVDLCIYSLHLKDLLHLDTALRQEKHMMFIQIF
KMCLLDLLPKKKSDDELYQKILSKQEKDLEELEKGLQVKLSNTEMSGAGDSEYITLADVE
KKEREYSEQLIDNMEAFWKQMANIQHFLVDQFKCSSSKARQLMMTLTERMIAAEGLLCDS
QELQALDALERTMGRAHMAKVIEFLKLQVQEETRCRLAAISHGLELLAGEGKLSGRQKEE
LLTQQHKAFWQEAERFSREFVQRGKDLVTASLAHQVEGTAKLTLAQEEEQRSFLAEAQPT
ADPEKFLEAFHEVLERQRLMQCDLEEEENVRATEAVVALCQELYFSTVDTFQKFVDALFL
QTLPGMTGLPPEECDYLRQEVQENAAWQLGKSNRFRRQQWKLFQELLEQDQQVWMEECAL
SSVLQTHLREDHEGTIRGVLGRLGGLTEESTRCVLQGHDLLLRSALRRLALRGNALATLT
QMRLSGKKHLLQELREQRALEQGSSQCLDEHQWQLLRALEARVLEEASRLEEEAQQTRLQ
LQQRLLAEAQEVGQLLQQHMECAIGQALLVHARNAATKSRAKDRDDFKRTLMEAAVESVY
VTSAGVSRLVQAYYQQIGRIMEDHEERKLQHLKTLQGERMENYKLRKKQELSNPSSGSRT
AGGAHETSQAVHQRMLSQQKRFLAQFPVHQQMRLHAQQQQAGVMDLLEAQLETQLQEAEQ
NFISELAALARVPLAESKLLPAKRGLLEKPLRTKRKKPLPQERGDLGVPNNEDLASGDQT
SGSLSSKRLSQQESEAGDSGNSKKMLKRRSNL
Function Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Involved in endochondral growth and skeletal development.
Tissue Specificity Found in the developing vertebral bodies, ribs, upper and lower limbs, heart, kidney, lung.
KEGG Pathway
Hedgehog sig.ling pathway (hsa04340 )
Reactome Pathway
Activation of SMO (R-HSA-5635838 )
Hedgehog 'on' state (R-HSA-5632684 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acrofacial dysostosis, Weyers type DISA9EM1 Definitive Autosomal recessive [1]
Ellis-van Creveld syndrome DISWSKIF Definitive Autosomal recessive [2]
Wolfram syndrome DISN16XW Definitive Biomarker [3]
Atrial septal defect DISJT76B Strong Genetic Variation [4]
Bipolar disorder DISAM7J2 Strong Genetic Variation [5]
Congenital deformities of limbs DISP4N1Q Strong Genetic Variation [6]
Congenital heart disease DISQBA23 Strong Genetic Variation [7]
Dysplasia DISHPNVX Strong Genetic Variation [8]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [9]
Ventricular septal defect DISICO41 Strong Genetic Variation [7]
Achondroplasia DISYWN2O moderate Biomarker [10]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of EvC complex member EVC (EVC). [11]
Tretinoin DM49DUI Approved Tretinoin increases the expression of EvC complex member EVC (EVC). [12]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of EvC complex member EVC (EVC). [13]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of EvC complex member EVC (EVC). [14]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of EvC complex member EVC (EVC). [15]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of EvC complex member EVC (EVC). [16]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of EvC complex member EVC (EVC). [17]
Testosterone DM7HUNW Approved Testosterone decreases the expression of EvC complex member EVC (EVC). [17]
Marinol DM70IK5 Approved Marinol increases the expression of EvC complex member EVC (EVC). [18]
Selenium DM25CGV Approved Selenium increases the expression of EvC complex member EVC (EVC). [19]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of EvC complex member EVC (EVC). [21]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of EvC complex member EVC (EVC). [22]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of EvC complex member EVC (EVC). [24]
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⏷ Show the Full List of 13 Drug(s)
2 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 affects the methylation of EvC complex member EVC (EVC). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of EvC complex member EVC (EVC). [23]
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References

1 A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. Mol Genet Metab. 2002 Dec;77(4):291-5. doi: 10.1016/s1096-7192(02)00178-6.
2 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.
3 Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.Int J Mol Med. 2004 Nov;14(5):903-7.
4 A novel mutation of GATA4 in a familial atrial septal defect.Clin Chim Acta. 2010 Nov 11;411(21-22):1741-5. doi: 10.1016/j.cca.2010.07.021. Epub 2010 Jul 24.
5 Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder.Mol Psychiatry. 2015 Oct;20(10):1212-8. doi: 10.1038/mp.2014.118. Epub 2014 Oct 14.
6 Molecular determinants of atrial and ventricular septal defects and patent ductus arteriosus.Am J Med Genet. 2000 Winter;97(4):304-9. doi: 10.1002/1096-8628(200024)97:4<304::aid-ajmg1281>3.0.co;2-#.
7 Molecular mechanisms of Ellisvan Creveld gene variations in ventricular septal defect.Mol Med Rep. 2018 Jan;17(1):1527-1536. doi: 10.3892/mmr.2017.8088. Epub 2017 Nov 15.
8 Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling.Hum Mutat. 2009 Dec;30(12):1667-75. doi: 10.1002/humu.21117.
9 Two novel susceptibility loci for type 2 diabetes mellitus identified by longitudinal exome-wide association studies in a Japanese population.Genomics. 2019 Jan;111(1):34-42. doi: 10.1016/j.ygeno.2017.12.010. Epub 2017 Dec 19.
10 The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16.Genomics. 1996 Jul 1;35(1):1-5. doi: 10.1006/geno.1996.0315.
11 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
12 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
13 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
14 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.
15 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
16 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.
17 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
18 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
19 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
20 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
21 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
22 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.
23 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.
24 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.