Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3NY6O6)

• DOT Name: Intraflagellar transport protein 27 homolog (IFT27)
• Synonyms: Putative GTP-binding protein RAY-like; Rab-like protein 4
• Gene Name: IFT27
• Related Disease:
  Bilateral renal agenesis
  Renal agenesis
  Renal hypodysplasia/aplasia 1
  Bardet-Biedl syndrome 19
  Bipolar disorder
  Ciliopathy
  Polydactyly
  Bardet biedl syndrome
• UniProt ID: IFT27_HUMAN
• Pfam ID: PF00071
• Sequence:
  MVKLAAKCILAGDPAVGKTALAQIFRSDGAHFQKSYTLTTGMDLVVKTVPVPDTGDSVEL
  FIFDSAGKELFSEMLDKLWESPNVLCLVYDVTNEESFNNCSKWLEKARSQAPGISLPGVL
  VGNKTDLAGRRAVDSAEARAWALGQGLECFETSVKEMENFEAPFHCLAKQFHQLYREKVE
  VFRALA
• Function: Small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6. Not involved in entry of the BBSome complex into cilium. Prevents aggregation of GTP-free ARL6. Required for hedgehog signaling. Forms a subcomplex within the IFT complex B with IFT25. Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation. Plays a role in the early development of the kidney. May be involved in the regulation of ureteric bud initiation.
• Reactome Pathway: Intraflagellar transport (R-HSA-5620924)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bilateral renal agenesis	DISOR5IA	Definitive	Genetic Variation	[1]
Renal agenesis	DIS0M9AF	Definitive	Genetic Variation	[1]
Renal hypodysplasia/aplasia 1	DISOH8XN	Definitive	Genetic Variation	[1]
Bardet-Biedl syndrome 19	DIS2PQ9X	Strong	Autosomal recessive	[2]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[3]
Ciliopathy	DIS10G4I	Strong	Biomarker	[4]
Polydactyly	DIS25BMZ	moderate	Biomarker	[1]
Bardet biedl syndrome	DISTBNZW	Supportive	Autosomal recessive	[2]

9 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 27 homolog (IFT27).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Intraflagellar transport protein 27 homolog (IFT27).	[10]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[12]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Intraflagellar transport protein 27 homolog (IFT27).	[13]

References

• [1] Loss of function IFT27 variants associated with an unclassified lethal fetal ciliopathy with renal agenesis.Am J Med Genet A. 2018 Jul;176(7):1610-1613. doi: 10.1002/ajmg.a.38685. Epub 2018 Apr 27.
• [2] IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Hum Mol Genet. 2014 Jun 15;23(12):3307-15. doi: 10.1093/hmg/ddu044. Epub 2014 Jan 31.
• [3] Evidence for association of bipolar disorder to haplotypes in the 22q12.3 region near the genes stargazin, IFT27 and parvalbumin.Am J Med Genet B Neuropsychiatr Genet. 2012 Dec;159B(8):941-50. doi: 10.1002/ajmg.b.32099. Epub 2012 Oct 4.
• [4] Ift25 is not a cystic kidney disease gene but is required for early steps of kidney development.Mech Dev. 2018 Jun;151:10-17. doi: 10.1016/j.mod.2018.04.001. Epub 2018 Apr 4.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [12] 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.
• [13] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.