Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6F9R7P)

• DOT Name: Transcription factor HES-7 (HES7)
• Synonyms: hHes7; Class B basic helix-loop-helix protein 37; bHLHb37; Hairy and enhancer of split 7; bHLH factor Hes7
• Gene Name: HES7
• Related Disease:
  Sickle-cell anaemia
  Systemic primary carnitine deficiency disease
  Coats plus syndrome
  Dysplasia
  Lung adenocarcinoma
  Spondylocostal dysostosis 2, autosomal recessive
  Spondylocostal dysostosis 4, autosomal recessive
  Autosomal recessive spondylocostal dysostosis
  Advanced cancer
  Spondylocostal dysostosis
• UniProt ID: HES7_HUMAN
• Pfam ID: PF00010
• Sequence:
  MVTRDRAENRDGPKMLKPLVEKRRRDRINRSLEELRLLLLERTRDQNLRNPKLEKAEILE
  FAVGYLRERSRVEPPGVPRSPVQDAEALASCYLSGFRECLLRLAAFAHDASPAARAQLFS
  ALHGYLRPKPPRPKPVDPRPPAPRPSLDPAAPALGPALHQRPPVHQGHPSPRCAWSPSLC
  SPRAGDSGAPAPLTGLLPPPPPPHRQDGAPKAPLPPPPAFWRPWP
• Function: Transcriptional repressor. Represses transcription from both N box- and E box-containing promoters. May with HES1, cooperatively regulate somite formation in the presomitic mesoderm (PSM). May function as a segmentation clock, which is essential for coordinated somite segmentation.
• KEGG Pathway: Human papillomavirus infection (hsa05165)
• Reactome Pathway: Somitogenesis (R-HSA-9824272)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sickle-cell anaemia	DIS5YNZB	Definitive	Genetic Variation	[1]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Definitive	Genetic Variation	[1]
Coats plus syndrome	DIS11ELA	Strong	Genetic Variation	[2]
Dysplasia	DISHPNVX	Strong	Genetic Variation	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Spondylocostal dysostosis 2, autosomal recessive	DISR3NXE	Strong	Genetic Variation	[5]
Spondylocostal dysostosis 4, autosomal recessive	DIS3HQRC	Strong	Autosomal recessive	[6]
Autosomal recessive spondylocostal dysostosis	DISAJI27	Supportive	Autosomal recessive	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]
Spondylocostal dysostosis	DISTPWFK	Limited	Genetic Variation	[9]

5 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 Transcription factor HES-7 (HES7).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor HES-7 (HES7).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor HES-7 (HES7).	[12]
CHIR-99021	DMB8MNU	Patented	CHIR-99021 increases the expression of Transcription factor HES-7 (HES7).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor HES-7 (HES7).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor HES-7 (HES7).	[13]

References

• [1] Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis.Eur J Hum Genet. 2010 Jun;18(6):674-9. doi: 10.1038/ejhg.2009.241. Epub 2010 Jan 20.
• [2] Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation.BMC Med Genet. 2015 Feb 10;16:5. doi: 10.1186/s12881-015-0151-8.
• [3] Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis.Hum Mol Genet. 2008 Dec 1;17(23):3761-6. doi: 10.1093/hmg/ddn272. Epub 2008 Sep 5.
• [4] Epithelial-mesenchymal transition markers screened in a cell-based model and validated in lung adenocarcinoma.BMC Cancer. 2019 Jul 11;19(1):680. doi: 10.1186/s12885-019-5885-9.
• [5] Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.PLoS One. 2015 Feb 6;10(2):e0117055. doi: 10.1371/journal.pone.0117055. eCollection 2015.
• [6] Dynamic expression and essential functions of Hes7 in somite segmentation. Genes Dev. 2001 Oct 15;15(20):2642-7. doi: 10.1101/gad.930601.
• [7] Spondylocostal Dysostosis, Autosomal Recessive. 2009 Aug 25 [updated 2023 Aug 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [8] Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors.PLoS One. 2017 Aug 2;12(8):e0180541. doi: 10.1371/journal.pone.0180541. eCollection 2017.
• [9] An InVitro Human Segmentation Clock Model Derived from Embryonic Stem Cells.Cell Rep. 2019 Aug 27;28(9):2247-2255.e5. doi: 10.1016/j.celrep.2019.07.090.
• [10] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.