Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFIVV9A)

DOT Name Intraflagellar transport protein 52 homolog (IFT52)
Synonyms Protein NGD5 homolog
Gene Name IFT52
Related Disease
Ciliopathy ( )
Gastrointestinal stromal tumour ( )
Polydactyly ( )
Retinopathy ( )
Short-rib thoracic dysplasia 16 with or without polydactyly ( )
Cranioectodermal dysplasia 1 ( )
Short rib-polydactyly syndrome ( )
Cranioectodermal dysplasia ( )
UniProt ID
IFT52_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF09822 ; PF21178
Sequence
MEKELRSTILFNAYKKEIFTTNNGYKSMQKKLRSNWKIQSLKDEITSEKLNGVKLWITAG
PREKFTAAEFEILKKYLDTGGDVFVMLGEGGESRFDTNINFLLEEYGIMVNNDAVVRNVY
HKYFHPKEALVSSGVLNREISRAAGKAVPGIIDEESSGNNAQALTFVYPFGATLSVMKPA
VAVLSTGSVCFPLNRPILAFYHSKNQGGKLAVLGSCHMFSDQYLDKEENSKIMDVVFQWL
TTGDIHLNQIDAEDPEISDYMMLPYTATLSKRNRECLQESDEIPRDFTTLFDLSIFQLDT
TSFHSVIEAHEQLNVKHEPLQLIQPQFETPLPTLQPAVFPPSFRELPPPPLELFDLDETF
SSEKARLAQITNKCTEEDLEFYVRKCGDILGVTSKLPKDQQDAKHILEHVFFQVVEFKKL
NQEHDIDTSETAFQNNF
Function
Involved in ciliogenesis as part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia. Required for the anterograde transport of IFT88.
Reactome Pathway
Intraflagellar transport (R-HSA-5620924 )
Hedgehog 'off' state (R-HSA-5610787 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ciliopathy DIS10G4I Strong Genetic Variation [1]
Gastrointestinal stromal tumour DIS6TJYS Strong Biomarker [2]
Polydactyly DIS25BMZ Strong Biomarker [3]
Retinopathy DISB4B0F Strong Genetic Variation [1]
Short-rib thoracic dysplasia 16 with or without polydactyly DISMCOEZ Strong Autosomal recessive [4]
Cranioectodermal dysplasia 1 DISN81L4 moderate Genetic Variation [5]
Short rib-polydactyly syndrome DISY2RES moderate Genetic Variation [6]
Cranioectodermal dysplasia DISW7Y64 Supportive Autosomal recessive [3]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Intraflagellar transport protein 52 homolog (IFT52). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Intraflagellar transport protein 52 homolog (IFT52). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Intraflagellar transport protein 52 homolog (IFT52). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Intraflagellar transport protein 52 homolog (IFT52). [10]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Intraflagellar transport protein 52 homolog (IFT52). [11]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Intraflagellar transport protein 52 homolog (IFT52). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Intraflagellar transport protein 52 homolog (IFT52). [14]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Intraflagellar transport protein 52 homolog (IFT52). [15]
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⏷ Show the Full List of 8 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 decreases the methylation of Intraflagellar transport protein 52 homolog (IFT52). [13]
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References

1 IFT52 as a Novel Candidate for Ciliopathies Involving Retinal Degeneration.Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4581-4589. doi: 10.1167/iovs.17-23351.
2 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.
3 A homozygous nonsense variant in IFT52 is associated with a human skeletal ciliopathy. Clin Genet. 2016 Dec;90(6):536-539. doi: 10.1111/cge.12762. Epub 2016 Mar 15.
4 Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons. Neuron. 2004 Jun 10;42(5):703-16. doi: 10.1016/s0896-6273(04)00268-5.
5 Human IFT52 mutations uncover a novel role for the protein in microtubule dynamics and centrosome cohesion.Hum Mol Genet. 2019 Aug 15;28(16):2720-2737. doi: 10.1093/hmg/ddz091.
6 IFT52 mutations destabilize anterograde complex assembly, disrupt ciliogenesis and result in short rib polydactyly syndrome. Hum Mol Genet. 2016 Sep 15;25(18):4012-4020. doi: 10.1093/hmg/ddw241. Epub 2016 Jul 27.
7 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
8 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.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 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.
13 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.
14 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.
15 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.