Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTERV7NW)

• DOT Name: Protein EURL homolog (C21ORF91)
• Gene Name: C21ORF91
• Related Disease: Herpes simplex labialis
• UniProt ID: EURL_HUMAN
• Pfam ID: PF06937
• Sequence:
  MNEEEQFVNIDLNDDNICSVCKLGTDKETLSFCHICFELNIEGVPKSDLLHTKSLRGHKD
  CFEKYHLIANQGCPRSKLSKSTYEEVKTILSKKINWIVQYAQNKDLDSDSECSKNPQHHL
  FNFRHKPEEKLLPQFDSQVPKYSAKWIDGSAGGISNCTQRILEQRENTDFGLSMLQDSGA
  TLCRNSVLWPHSHNQAQKKEETISSPEANVQTQHPHYSREELNSMTLGEVEQLNAKLLQQ
  IQEVFEELTHQVQEKDSLASQLHVRHVAIEQLLKNCSKLPCLQVGRTGMKSHLPINN
• Function: Plays a role in cortical progenitor cell proliferation and differentiation. Promotes dendritic spine development of post-migratory cortical projection neurons by modulating the beta-catenin signaling pathway.
• Tissue Specificity: Expressed in the brain . Expressed in cortical cells of the germinal ventricular zone and the cortical plate. Underexpressed in the dorsolateral prefrontal cortex, primary visual cortex and cerebellar cortex compared with Down Syndrome patients (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Herpes simplex labialis	DISC5STS	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein EURL homolog (C21ORF91).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein EURL homolog (C21ORF91).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein EURL homolog (C21ORF91).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein EURL homolog (C21ORF91).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein EURL homolog (C21ORF91).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein EURL homolog (C21ORF91).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein EURL homolog (C21ORF91).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein EURL homolog (C21ORF91).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein EURL homolog (C21ORF91).	[10]

References

• [1] C21orf91 genotypes correlate with herpes simplex labialis (cold sore) frequency: description of a cold sore susceptibility gene.J Infect Dis. 2011 Dec 1;204(11):1654-62. doi: 10.1093/infdis/jir633.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [5] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.