Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY0M5SD)

DOT Name Limbin (EVC2)
Synonyms Ellis-van Creveld syndrome protein 2; EVC2
Gene Name EVC2
Related Disease
Acrofacial dysostosis, Weyers type ( )
Ellis-van Creveld syndrome ( )
Ciliopathy ( )
Cleft palate ( )
Dysplasia ( )
Hereditary hemochromatosis ( )
Human papillomavirus infection ( )
Isolated cleft palate ( )
Myopathy ( )
Postaxial polydactyly ( )
Visceral heterotaxy ( )
Dental enamel hypoplasia ( )
UniProt ID
LBN_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12297
Sequence
MDPSGSRGRPTWVLAGGLLAVALALGGRGCLGASSRPRWRPLGAQPPRDPQVAPRSGPGL
RIPPGRSGAGPESSTQDLPCMIWPKVECCHFKTAVEAPLGMKLDKKMEVFIPLSTSAASS
GPWAHSLFAFIPSWPKKNLFKRESPITHRLYGDISREVQGTSENGVIFQKCALVSGSSEA
QTARIWLLVNNTKTTSSANLSELLLLDSIAGLTIWDSVGNRTSEGFQAFSKKFLQVGDAF
AVSYAATLQAGDLGNGESLKLPAQLTFQSSSRNRTQLKVLFSITAEENVTVLPHHGLHAA
GFFIAFLLSLVLTWAALFLMVRYQCLKGNMLTRHRVWQYESKLEPLPFTSADGVNEDLSL
NDQMIDILSSEDPGSMLQALEELEIATLNRADADLEACRTQISKDIIALLLKNLTSSGHL
SPQVERKMSAVFKKQFLLLENEIQEEYDRKMVALTAECDLETRKKMENQYQREMMAMEEA
EELLKRAGERSAVECSNLLRTLHGLEQEHLRKSLALQQEEDFAKAHRQLAVFQRNELHSI
FFTQIKSAIFKGELKPEAAKMLLQNYSKIQENVEELMDFFQASKRYHLSKRFGHREYLVQ
NLQSSETRVQGLLSTAAAQLTHLIQKHERAGYLDEDQMEMLLERAQTEVFSIKQKLDNDL
KQEKKKLHQKLITKRRRELLQKHREQRREQASVGEAFRTVEDAGQYLHQKRSLMEEHGAT
LEELQERLDQAALDDLRTLTLSLFEKATDELRRLQNSAMTQELLKRGVPWLFLQQILEEH
GKEMAARAEQLEGEERDRDQEGVQSVRQRLKDDAPEAVTEEQAELRRWEHLIFMKLCSSV
FSLSEEELLRMRQEVHGCFAQMDRSLALPKIRARVLLQQFQTAWREAEFVKLDQAVAAPE
LQQQSKVRKSRSKSKSKGELLKKCIEDKIHLCEEQASEDLVEKVRGELLRERVQRMEAQE
GGFAQSLVALQFQKASRVTETLSAYTALLSIQDLLLEELSASEMLTKSACTQILESHSRE
LQELERKLEDQLVQQEAAQQQQALASWQQWVADGPGILNEPGEVDSERQVSTVLHQALSK
SQTLLEQHQQCLREEQQNSVVLEDLLENMEADTFATLCSQELRLASYLARMAMVPGATLR
RLLSVVLPTASQPQLLALLDSATERHVDHAAESDGGAEQADVGRRRKHQSWWQALDGKLR
GDLISRGLEKMLWARKRKQSILKKTCLPLRERMIFSGKGSWPHLSLEPIGELAPVPIVGA
ETIDLLNTGEKLFIFRNPKEPEISLHVPPRKKKNFLNAKKAMRALGMD
Function
Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Plays a critical role in bone formation and skeletal development. May be involved in early embryonic morphogenesis.
Tissue Specificity Found in the heart, placenta, lung, liver, skeletal muscle, kidney and pancreas.
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

12 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]
Ciliopathy DIS10G4I Strong Biomarker [3]
Cleft palate DIS6G5TF Strong Genetic Variation [4]
Dysplasia DISHPNVX Strong Genetic Variation [1]
Hereditary hemochromatosis DISVG5MT Strong Biomarker [5]
Human papillomavirus infection DISX61LX Strong Biomarker [6]
Isolated cleft palate DISV80CD Strong Genetic Variation [4]
Myopathy DISOWG27 Strong Genetic Variation [7]
Postaxial polydactyly DIS085OV Strong Genetic Variation [8]
Visceral heterotaxy DIS1DV90 Strong Biomarker [9]
Dental enamel hypoplasia DISN6ZMR Limited Genetic Variation [10]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Limbin (EVC2). [11]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Limbin (EVC2). [12]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Limbin (EVC2). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Limbin (EVC2). [15]
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1 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 decreases the methylation of Limbin (EVC2). [14]
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References

1 A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial dysostosis. Hum Genet. 2006 Mar;119(1-2):199-205. doi: 10.1007/s00439-005-0129-2. Epub 2006 Jan 11.
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 Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice.PLoS Genet. 2016 Dec 27;12(12):e1006510. doi: 10.1371/journal.pgen.1006510. eCollection 2016 Dec.
4 Association between genes on chromosome 4p16 and non-syndromic oral clefts in four populations.Eur J Hum Genet. 2010 Jun;18(6):726-32. doi: 10.1038/ejhg.2009.228. Epub 2010 Jan 20.
5 Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2.Cell Res. 2012 Nov;22(11):1593-604. doi: 10.1038/cr.2012.134. Epub 2012 Sep 18.
6 Infection and HLA-G molecules in nasal polyposis.J Immunol Res. 2014;2014:407430. doi: 10.1155/2014/407430. Epub 2014 Mar 6.
7 Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.Clin Pharmacol Ther. 2019 Dec;106(6):1353-1361. doi: 10.1002/cpt.1557. Epub 2019 Jul 31.
8 Ellis-van Creveld syndrome: prenatal diagnosis, molecular analysis and genetic counseling.Taiwan J Obstet Gynecol. 2010 Dec;49(4):481-6. doi: 10.1016/S1028-4559(10)60101-5.
9 Ellis-van Creveld syndrome and congenital heart defects: presentation of an additional 32 cases.Pediatr Cardiol. 2011 Oct;32(7):977-82. doi: 10.1007/s00246-011-0006-9. Epub 2011 May 1.
10 Loss of Function of Evc2 in Dental Mesenchyme Leads to Hypomorphic Enamel.J Dent Res. 2017 Apr;96(4):421-429. doi: 10.1177/0022034516683674. Epub 2017 Jan 12.
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 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
13 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
14 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.
15 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.