Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKWYQ5C)

• DOT Name: Intraflagellar transport protein 43 homolog (IFT43)
• Gene Name: IFT43
• Related Disease:
  Cranioectodermal dysplasia 3
  Myopia
  Alzheimer disease
  Cranioectodermal dysplasia 1
  Intellectual disability
  Loeys-Dietz syndrome 4
  Short-rib thoracic dysplasia 18 with polydactyly
  Polydactyly
  Cranioectodermal dysplasia
  Angioedema
  Retinitis pigmentosa 81
  Urticaria
• UniProt ID: IFT43_HUMAN
• PDB ID: 8BBE; 8BBG; 8FGW
• Pfam ID: PF15305
• Sequence:
  MEDLLDLDEELRYSLATSRAKMGRRAQQESAQAENHLNGKNSSLTLTGETSSAKLPRCRQ
  GGWAGDSVKASKFRRKASEEIEDFRLRPQSLNGSDYGGDIPIIPDLEEVQEEDFVLQVAA
  PPSIQIKRVMTYRDLDNDLMKYSAIQTLDGEIDLKLLTKVLAPEHEVREDDVGWDWDHLF
  TEVSSEVLTEWDPLQTEKEDPAGQARHT
• Function: As a component of IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis. Involved in retrograde ciliary transport along microtubules from the ciliary tip to the base.
• Tissue Specificity: Expressed in the retina, predominantly in the photoreceptor outer segment.
• Reactome Pathway: Intraflagellar transport (R-HSA-5620924)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cranioectodermal dysplasia 3	DIS5TX0M	Definitive	Autosomal recessive	[1]
Myopia	DISK5S60	Definitive	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Cranioectodermal dysplasia 1	DISN81L4	Strong	Biomarker	[4]
Intellectual disability	DISMBNXP	Strong	Biomarker	[2]
Loeys-Dietz syndrome 4	DISG09TJ	Strong	Genetic Variation	[5]
Short-rib thoracic dysplasia 18 with polydactyly	DISO19BP	Strong	Biomarker	[4]
Polydactyly	DIS25BMZ	moderate	Biomarker	[6]
Cranioectodermal dysplasia	DISW7Y64	Supportive	Autosomal recessive	[7]
Angioedema	DIS90QDN	Limited	Genetic Variation	[8]
Retinitis pigmentosa 81	DISQN9KL	Limited	Unknown	[9]
Urticaria	DIS9WQAI	Limited	Genetic Variation	[8]

7 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 43 homolog (IFT43).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Intraflagellar transport protein 43 homolog (IFT43).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Intraflagellar transport protein 43 homolog (IFT43).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Intraflagellar transport protein 43 homolog (IFT43).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Intraflagellar transport protein 43 homolog (IFT43).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Intraflagellar transport protein 43 homolog (IFT43).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Intraflagellar transport protein 43 homolog (IFT43).	[14]

References

• [1] C14ORF179 encoding IFT43 is mutated in Sensenbrenner syndrome. J Med Genet. 2011 Jun;48(6):390-5. doi: 10.1136/jmg.2011.088864. Epub 2011 Mar 4.
• [2] De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia.Am J Med Genet A. 2016 Jun;170(6):1566-9. doi: 10.1002/ajmg.a.37598. Epub 2016 Feb 19.
• [3] Expression of ced-3 and ced-9 homologs in Alzheimer's disease cerebral cortex.Neurosci Lett. 1998 Mar 13;244(2):69-72. doi: 10.1016/s0304-3940(98)00138-4.
• [4] [Clinical features and mutational analysis of a case with Sensenbrenner syndrome].Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018 Jun 10;35(3):426-428. doi: 10.3760/cma.j.issn.1003-9406.2018.03.027.
• [5] Mutations in a TGF- ligand, TGFB3, cause syndromic aortic aneurysms and dissections.J Am Coll Cardiol. 2015 Apr 7;65(13):1324-1336. doi: 10.1016/j.jacc.2015.01.040.
• [6] Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.Cilia. 2017 Apr 10;6:7. doi: 10.1186/s13630-017-0051-y. eCollection 2017.
• [7] Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):165-74. doi: 10.1002/ajmg.c.31336. Epub 2012 Jul 12.
• [8] Genome-wide association study in NSAID-induced acute urticaria/angioedema in Spanish and Han Chinese populations.Pharmacogenomics. 2013 Nov;14(15):1857-69. doi: 10.2217/pgs.13.166.
• [9] A mutation in IFT43 causes non-syndromic recessive retinal degeneration. Hum Mol Genet. 2017 Dec 1;26(23):4741-4751. doi: 10.1093/hmg/ddx356.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.