Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB23T17)

DOT Name Intraflagellar transport protein 81 homolog (IFT81)
Synonyms Carnitine deficiency-associated protein expressed in ventricle 1; CDV-1
Gene Name IFT81
Related Disease
Cone-rod dystrophy 2 ( )
Inherited retinal dystrophy ( )
Jeune syndrome ( )
Multiple epiphyseal dysplasia ( )
Short-rib thoracic dysplasia 19 with or without polydactyly ( )
Ciliopathy ( )
UniProt ID
IFT81_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF18383
Sequence
MSDQIKFIMDSLNKEPFRKNYNLITFDSLEPMQLLQVLSDVLAEIDPKQLVDIREEMPEQ
TAKRMLSLLGILKYKPSGNATDMSTFRQGLVIGSKPVIYPVLHWLLQRTNELKKRAYLAR
FLIKLEVPSEFLQDETVADTNKQYEELMEAFKTLHKEYEQLKISGFSTAEIRKDISAMEE
EKDQLIKRVEHLKKRVETAQNHQWMLKIARQLRVEKEREEYLAQQKQEQKNQLFHAVQRL
QRVQNQLKSMRQAAADAKPESLMKRLEEEIKFNLYMVTEKFPKELENKKKELHFLQKVVS
EPAMGHSDLLELESKINEINTEINQLIEKKMMRNEPIEGKLSLYRQQASIISRKKEAKAE
ELQEAKEKLASLEREASVKRNQTREFDGTEVLKGDEFKRYVNKLRSKSTVFKKKHQIIAE
LKAEFGLLQRTEELLKQRHENIQQQLQTMEEKKGISGYSYTQEELERVSALKSEVDEMKG
RTLDDMSEMVKKLYSLVSEKKSALASVIKELRQLRQKYQELTQECDEKKSQYDSCAAGLE
SNRSKLEQEVRRLREECLQEESRYHYTNCMIKNLEVQLRRATDEMKAYISSDQQEKRKAI
REQYTKNTAEQENLGKKLREKQKVIRESHGPNMKQAKMWRDLEQLMECKKQCFLKQQSQT
SIGQVIQEGGEDRLIL
Function
Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds tubulin via its CH (calponin-homology)-like region. Required for ciliogenesis. Required for proper regulation of SHH signaling. Plays an important role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.
Tissue Specificity
Highly expressed in testis, moderately in ovary, heart, liver, skeletal muscle, kidney and pancreas, low in prostate, brain, placenta and lung and not detected in spleen, thymus, small intestine and colon. Isoform CDV-1R is abundantly expressed in testis.
Reactome Pathway
Intraflagellar transport (R-HSA-5620924 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cone-rod dystrophy 2 DISX2RWY Strong Genetic Variation [1]
Inherited retinal dystrophy DISGGL77 Strong Genetic Variation [1]
Jeune syndrome DISLC357 Strong Genetic Variation [2]
Multiple epiphyseal dysplasia DIS5FZLR Strong Genetic Variation [2]
Short-rib thoracic dysplasia 19 with or without polydactyly DISZUM4D Strong Autosomal recessive [3]
Ciliopathy DIS10G4I Limited Autosomal recessive [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 Intraflagellar transport protein 81 homolog (IFT81). [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [7]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Intraflagellar transport protein 81 homolog (IFT81). [8]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [9]
Selenium DM25CGV Approved Selenium decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [10]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [11]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Intraflagellar transport protein 81 homolog (IFT81). [13]
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⏷ Show the Full List of 10 Drug(s)
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 increases the methylation of Intraflagellar transport protein 81 homolog (IFT81). [12]
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References

1 IFT81 as a Candidate Gene for Nonsyndromic Retinal Degeneration.Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2483-2490. doi: 10.1167/iovs.16-19133.
2 Alu-Alu mediated intragenic duplications in IFT81 and MATN3 are associated with skeletal dysplasias.Hum Mutat. 2018 Oct;39(10):1456-1467. doi: 10.1002/humu.23605. Epub 2018 Aug 22.
3 IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype. J Med Genet. 2015 Oct;52(10):657-65. doi: 10.1136/jmedgenet-2014-102838. Epub 2015 Aug 14.
4 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.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 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.
9 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.
10 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.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
12 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.
13 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.