Details of Drug Off-Target (DOT)

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

• DOT Name: IQ domain-containing protein E (IQCE)
• Gene Name: IQCE
• Related Disease:
  Cystic kidney disease
  Food allergy
  Polydactyly
  Postaxial polydactyly
  Postaxial polydactyly type A
  Polydactyly, postaxial, type a7
• UniProt ID: IQCE_HUMAN
• Pfam ID: PF00612
• Sequence:
  MFLGTGEPALDTGDDSLSAVTFDSDVETKAKRKAFHKPPPTSPKSPYLSKPRKVASWRSL
  RTAGSMPLGGRASLTPQKLWLGTAKPGSLTQALNSPLTWEHAWTGVPGGTPDCLTDTFRV
  KRPHLRRSASNGHVPGTPVYREKEDMYDEIIELKKSLHVQKSDVDLMRTKLRRLEEENSR
  KDRQIEQLLDPSRGTDFVRTLAEKRPDASWVINGLKQRILKLEQQCKEKDGTISKLQTDM
  KTTNLEEMRIAMETYYEEVHRLQTLLASSETTGKKPLGEKKTGAKRQKKMGSALLSLSRS
  VQELTEENQSLKEDLDRVLSTSPTISKTQGYVEWSKPRLLRRIVELEKKLSVMESSKSHA
  AEPVRSHPPACLASSSALHRQPRGDRNKDHERLRGAVRDLKEERTALQEQLLQRDLEVKQ
  LLQAKADLEKELECAREGEEERREREEVLREEIQTLTSKLQELQEMKKEEKEDCPEVPHK
  AQELPAPTPSSRHCEQDWPPDSSEEGLPRPRSPCSDGRRDAAARVLQAQWKVYKHKKKKA
  VLDEAAVVLQAAFRGHLTRTKLLASKAHGSEPPSVPGLPDQSSPVPRVPSPIAQATGSPV
  QEEAIVIIQSALRAHLARARHSATGKRTTTAASTRRRSASATHGDASSPPFLAALPDPSP
  SGPQALAPLPGDDVNSDDSDDIVIAPSLPTKNFPV
• Function: Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Required for proper limb morphogenesis.
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)
• Reactome Pathway: Activation of SMO (R-HSA-5635838)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic kidney disease	DISRT1LM	Strong	Biomarker	[1]
Food allergy	DISMQ1BP	Strong	Genetic Variation	[2]
Polydactyly	DIS25BMZ	Strong	Genetic Variation	[3]
Postaxial polydactyly	DIS085OV	moderate	Biomarker	[1]
Postaxial polydactyly type A	DIS4IIPW	Supportive	Autosomal recessive	[4]
Polydactyly, postaxial, type a7	DISLLBGJ	Limited	Autosomal recessive	[5]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of IQ domain-containing protein E (IQCE).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of IQ domain-containing protein E (IQCE).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of IQ domain-containing protein E (IQCE).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of IQ domain-containing protein E (IQCE).	[11]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of IQ domain-containing protein E (IQCE).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of IQ domain-containing protein E (IQCE).	[8]

References

• [1] Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish.Hum Mutat. 2020 Jan;41(1):240-254. doi: 10.1002/humu.23924. Epub 2019 Oct 17.
• [2] Genome-wide association study of maternal genetic effects and parent-of-origin effects on food allergy.Medicine (Baltimore). 2018 Mar;97(9):e0043. doi: 10.1097/MD.0000000000010043.
• [3] Exome sequencing revealed a splice site variant in the IQCE gene underlying post-axial polydactyly type A restricted to lower limb. Eur J Hum Genet. 2017 Aug;25(8):960-965. doi: 10.1038/ejhg.2017.83. Epub 2017 May 10.
• [4] Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A. 2015 Dec;167A(12):2869-92. doi: 10.1002/ajmg.a.37365. Epub 2015 Sep 23.
• [5] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] 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.
• [11] 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.