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

DOT Name Intraflagellar transport protein 74 homolog (IFT74)
Synonyms Capillary morphogenesis gene 1 protein; CMG-1; Coiled-coil domain-containing protein 2
Gene Name IFT74
Related Disease
Bardet-Biedl syndrome 22 ( )
Bardet-Biedl syndrome 20 ( )
Oligospermia ( )
Schizophrenia ( )
Bardet biedl syndrome ( )
Amyotrophic lateral sclerosis ( )
Spermatogenic failure 58 ( )
UniProt ID
IFT74_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASNHKSSAARPVSRGGVGLTGRPPSGIRPLSGNIRVATAMPPGTARPGSRGCPIGTGGV
LSSQIKVAHRPVTQQGLTGMKTGTKGPQRQILDKSYYLGLLRSKISELTTEVNKLQKGIE
MYNQENSVYLSYEKRAETLAVEIKELQGQLADYNMLVDKLNTNTEMEEVMNDYNMLKAQN
DRETQSLDVIFTERQAKEKQIRSVEEEIEQEKQATDDIIKNMSFENQVKYLEMKTTNEKL
LQELDTLQQQLDSQNMKKESLEAEIAHSQVKQEAVLLHEKLYELESHRDQMIAEDKSIGS
PMEEREKLLKQIKDDNQEIASMERQLTDTKEKINQFIEEIRQLDMDLEEHQGEMNQKYKE
LKKREEHMDTFIETFEETKNQELKRKAQIEANIVALLEHCSRNINRIEQISSITNQELKM
MQDDLNFKSTEVQKSQSTAQNLTSDIQRLQLDLQKMELLESKMTEEQHSLKSKIKQMTTD
LEIYNDLPALKSSGEEKIKKLHQERMILSTHRNAFKKIMEKQNIEYEALKTQLQENETHS
QLTNLERKWQHLEQNNFAMKEFIATKSQESDYQPIKKNVTKQIAEYNKTIVDALHSTSGN
Function
Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds beta-tubulin via its basic region. Required for ciliogenesis. Essential for flagellogenesis during spermatogenesis.
Tissue Specificity
Highly expressed in adult and fetal kidney and expressed at lower level in adult heart, placenta, lung, liver and pancreas, and in fetal heart, lung and liver. Little to no expression was detected in adult brain and skeletal muscle or in fetal brain, thymus and spleen . Detected in sperm (at protein level) .
Reactome Pathway
Intraflagellar transport (R-HSA-5620924 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bardet-Biedl syndrome 22 DIS60BR4 Definitive Autosomal recessive [1]
Bardet-Biedl syndrome 20 DISXVC6U Strong Biomarker [2]
Oligospermia DIS6YJF3 Strong Genetic Variation [3]
Schizophrenia DISSRV2N Strong Genetic Variation [4]
Bardet biedl syndrome DISTBNZW Supportive Autosomal recessive [2]
Amyotrophic lateral sclerosis DISF7HVM Limited Genetic Variation [5]
Spermatogenic failure 58 DISJQ94R Limited Unknown [6]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 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 Intraflagellar transport protein 74 homolog (IFT74). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [10]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Intraflagellar transport protein 74 homolog (IFT74). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [12]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Intraflagellar transport protein 74 homolog (IFT74). [13]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Intraflagellar transport protein 74 homolog (IFT74). [14]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Intraflagellar transport protein 74 homolog (IFT74). [15]
Selenium DM25CGV Approved Selenium decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [16]
Progesterone DMUY35B Approved Progesterone increases the expression of Intraflagellar transport protein 74 homolog (IFT74). [17]
Enzalutamide DMGL19D Approved Enzalutamide affects the expression of Intraflagellar transport protein 74 homolog (IFT74). [18]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [21]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Intraflagellar transport protein 74 homolog (IFT74). [22]
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⏷ Show the Full List of 15 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the methylation of Intraflagellar transport protein 74 homolog (IFT74). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Intraflagellar transport protein 74 homolog (IFT74). [20]
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References

1 Third case of Bardet-Biedl syndrome caused by a biallelic variant predicted to affect splicing of IFT74. Clin Genet. 2021 Jul;100(1):93-99. doi: 10.1111/cge.13962. Epub 2021 Mar 27.
2 Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. Am J Hum Genet. 2016 Aug 4;99(2):318-36. doi: 10.1016/j.ajhg.2015.04.023.
3 Intraflagellar transport protein 74 is essential for spermatogenesis and male fertility in mice?"Shi L. Huang Q
4 Common variants conferring risk of schizophrenia.Nature. 2009 Aug 6;460(7256):744-7. doi: 10.1038/nature08186. Epub 2009 Jul 1.
5 Genetic studies of GRN and IFT74 in amyotrophic lateral sclerosis.Neurobiol Aging. 2008 Aug;29(8):1279-82. doi: 10.1016/j.neurobiolaging.2007.02.022. Epub 2007 Mar 23.
6 Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies. Hum Mutat. 2018 Jan;39(1):152-166. doi: 10.1002/humu.23362. Epub 2017 Nov 6.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
9 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.
10 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
11 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.
12 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 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.
15 Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
16 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.
17 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
18 NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
19 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.
20 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
21 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
22 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.