Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE0EG10)

• DOT Name: EF-hand calcium-binding domain-containing protein 7 (EFCAB7)
• Gene Name: EFCAB7
• Related Disease: Ellis-van Creveld syndrome
• UniProt ID: EFCB7_HUMAN
• Pfam ID: PF13499
• Sequence:
  MAISPRSDATFSSQKSTPSESPRTKKFPLTEEEIFYMNCRAAYLTVFKSSLENIISKDQL
  YLALQHAGRNPSQKTINKYWTPQTAKLNFDDFCIILRKEKPTSKAELLKSFKQLDVNDDG
  CILHTDLYKFLTKRGEKMTREEVNAIINLADVNADGKFDYIKFCKLYMTTNEQCLKTTLE
  KLEVDSKLMRHQFGNHIEGSPERDPSPVPKPSPKITRKTDPETFLNKGDTRSSLLSATRK
  FKTSVSFTVTMGANGNRNSKLMEPNLIKDWQHMQSKGCFFLEEDGEIISHQYRMQIAQRS
  MVYLTIKPLNLSQVEGKPSPWLSVDTALYILKENESQANLQLVCFTELRNREVFGWTGEL
  GPGIYWLIPSTTGCRLRKKIKPVTDEAQLVYRDETGELFLTKEFKSTLSDIFEVIDLDGN
  GLLSLEEYNFFELRTSGEKCDEDAWAVCRENFDTKRNELTRQGFMDLNLMEANDREGDPC
  DLWVTLHSMGYNKALELTEACPFVIDIYAEKCKPKIKAVHMEACSGQLEKAICKSVLSNG
  DAKVMDGYENIIVHTYSCDTWITSVIENKSDEKVIIHISNELSKNCINNRGLNIFAVEVG
  PKSTMVCQHVMPLNERQEWIYYCIYSLIS
• Function: Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Required for the localization of the EVC2:EVC subcomplex at the base of primary cilia.
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)
• Reactome Pathway: Activation of SMO (R-HSA-5635838)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ellis-van Creveld syndrome	DISWSKIF	Strong	Genetic Variation	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	EF-hand calcium-binding domain-containing protein 7 (EFCAB7) affects the response to substance of Doxorubicin.	[9]
Paclitaxel	DMLB81S	Approved	EF-hand calcium-binding domain-containing protein 7 (EFCAB7) affects the response to substance of Paclitaxel.	[9]
Vinblastine	DM5TVS3	Approved	EF-hand calcium-binding domain-containing protein 7 (EFCAB7) affects the response to substance of Vinblastine.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[4]

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 EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[8]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of EF-hand calcium-binding domain-containing protein 7 (EFCAB7).	[5]

References

• [1] Truncation and microdeletion of EVC/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome.Congenit Anom (Kyoto). 2016 Sep;56(5):209-16. doi: 10.1111/cga.12155.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.