Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIGAL0L)

• DOT Name: Intraflagellar transport protein 56 (IFT56)
• Synonyms: Tetratricopeptide repeat protein 26; TPR repeat protein 26
• Gene Name: IFT56
• Related Disease: Biliary, renal, neurologic, and skeletal syndrome
• UniProt ID: IFT56_HUMAN
• Pfam ID: PF12895
• Sequence:
  MMLSRAKPAVGRGVQHTDKRKKKGRKIPKLEELLSKRDFTGAITLLEFKRHVGEEEEDTN
  LWIGYCAFHLGDYKRALEEYENATKEENCNSEVWVNLACTYFFLGMYKQAEAAGFKASKS
  RLQNRLLFHLAHKFNDEKKLMSFHQNLQDVTEDQLSLASIHYMRSHYQEAIDIYKRILLD
  NREYLALNVYVALCYYKLDYYDVSQEVLAVYLQQIPDSTIALNLKACNHFRLYNGRAAEA
  ELKSLMDNASSSFEFAKELIRHNLVVFRGGEGALQVLPPLVDVIPEARLNLVIYYLRQDD
  VQEAYNLIKDLEPTTPQEYILKGVVNAALGQEMGSRDHMKIAQQFFQLVGGSASECDTIP
  GRQCMASCFFLLKQFDDVLIYLNSFKSYFYNDDIFNFNYAQAKAATGNTSEGEEAFLLIQ
  SEKMKNDYIYLSWLARCYIMNKKPRLAWELYLKMETSGESFSLLQLIANDCYKMGQFYYS
  AKAFDVLERLDPNPEYWEGKRGACVGIFQMIIAGREPKETLREVLHLLRSTGNTQVEYMI
  RIMKKWAKENRVSI
• Function: Component of the intraflagellar transport (IFT) complex B required for transport of proteins in the motile cilium. Required for transport of specific ciliary cargo proteins related to motility, while it is neither required for IFT complex B assembly or motion nor for cilium assembly. Required for efficient coupling between the accumulation of GLI2 and GLI3 at the ciliary tips and their dissociation from the negative regulator SUFU. Plays a key role in maintaining the integrity of the IFT complex B and the proper ciliary localization of the IFT complex B components. Not required for IFT complex A ciliary localization or function. Essential for maintaining proper microtubule organization within the ciliary axoneme.
• Reactome Pathway: Intraflagellar transport (R-HSA-5620924)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Biliary, renal, neurologic, and skeletal syndrome	DISC54HY	Strong	Autosomal recessive	[1]

6 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 56 (IFT56).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Intraflagellar transport protein 56 (IFT56).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Intraflagellar transport protein 56 (IFT56).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Intraflagellar transport protein 56 (IFT56).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Intraflagellar transport protein 56 (IFT56).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Intraflagellar transport protein 56 (IFT56).	[9]

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 Intraflagellar transport protein 56 (IFT56).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Intraflagellar transport protein 56 (IFT56).	[8]

References

• [1] Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Mol Biol Cell. 2012 Aug;23(16):3069-78. doi: 10.1091/mbc.E12-01-0019. Epub 2012 Jun 20.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.