Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXDJ9R8)

• DOT Name: EF-hand calcium-binding domain-containing protein 11 (EFCAB11)
• Gene Name: EFCAB11
• Related Disease:
  Hepatocellular carcinoma
  Schizophrenia
• UniProt ID: EFC11_HUMAN
• Pfam ID: PF13499 ; PF13833
• Sequence:
  MFFSEARARSRTWEASPSEHRKWVEVFKACDEDHKGYLSREDFKTAVVMLFGYKPSKIEV
  DSVMSSINPNTSGILLEGFLNIVRKKKEAQRYRNEVRHIFTAFDTYYRGFLTLEDFKKAF
  RQVAPKLPERTVLEVFREVDRDSDGHVSFRDFEYALNYGQKEA

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	EF-hand calcium-binding domain-containing protein 11 (EFCAB11) increases the Metabolic disorder ADR of Chlorothiazide.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of EF-hand calcium-binding domain-containing protein 11 (EFCAB11).	[12]

References

• [1] Replication the association of 2q32.2-q32.3 and 14q32.11 with hepatocellular carcinoma.Gene. 2015 Apr 25;561(1):63-7. doi: 10.1016/j.gene.2015.02.006. Epub 2015 Feb 7.
• [2] 22q11.2 deletion carriers and schizophrenia-associated novel variants.Br J Psychiatry. 2014;204:398-9. doi: 10.1192/bjp.bp.113.138420. Epub 2014 Jan 30.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] 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.
• [12] 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.
• [13] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.