Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLSVD17)

• DOT Name: Class E basic helix-loop-helix protein 23 (BHLHE23)
• Synonyms: bHLHe23; Class B basic helix-loop-helix protein 4; bHLHb4
• Gene Name: BHLHE23
• Related Disease:
  Alzheimer disease
  Non-alcoholic fatty liver disease
  Squamous cell carcinoma
  Megacystis-microcolon-intestinal hypoperistalsis syndrome
  Epidermolysis bullosa simplex
  Lung cancer
  Lung carcinoma
  Non-alcoholic steatohepatitis
• UniProt ID: BHE23_HUMAN
• Pfam ID: PF00010
• Sequence:
  MAELKSLSGDAYLALSHGYAAAAAGLAYGAAREPEAARGYGTPGPGGDLPAAPAPRAPAQ
  AAESSGEQSGDEDDAFEQRRRRRGPGSAADGRRRPREQRSLRLSINARERRRMHDLNDAL
  DGLRAVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALDEMRRLVAFLNQGQGLAAPVNA
  APLTPFGQATVCPFSAGAALGPCPDKCAAFSGTPSALCKHCHEKP
• Function: May function as transcriptional repressor. May modulate the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types. May be important for rod bipolar cell maturation.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[3]
Megacystis-microcolon-intestinal hypoperistalsis syndrome	DIS9KV47	Disputed	Biomarker	[4]
Epidermolysis bullosa simplex	DIS2CZ6X	Limited	Genetic Variation	[5]
Lung cancer	DISCM4YA	Limited	Altered Expression	[6]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[6]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[7]

2 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 Class E basic helix-loop-helix protein 23 (BHLHE23).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Class E basic helix-loop-helix protein 23 (BHLHE23).	[9]

References

• [1] Anti-inflammatory potential of thymosin 4 in the central nervous system: implications for progressive neurodegenerative diseases.Expert Opin Biol Ther. 2018 Jul;18(sup1):165-169. doi: 10.1080/14712598.2018.1486817.
• [2] Association between thymosin beta4 and non-alcoholic fatty liver disease.Rev Esp Enferm Dig. 2019 Apr;111(4):308-313. doi: 10.17235/reed.2019.5927/2018.
• [3] Metastatic growth of squamous cell carcinomas is correlated with upregulation and redistribution of hemidesmosomal components.Cell Tissue Res. 2001 Dec;306(3):399-408. doi: 10.1007/s004410100462. Epub 2001 Oct 23.
• [4] Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and CHRNB4.J Hum Genet. 2001;46(7):362-6. doi: 10.1007/PL00010921.
• [5] Deletion of a cytoplasmic domain of integrin beta4 causes epidermolysis bullosa simplex.J Invest Dermatol. 2002 Dec;119(6):1275-81. doi: 10.1046/j.1523-1747.2002.19609.x.
• [6] New insights into Vinca alkaloids resistance mechanism and circumvention in lung cancer.Biomed Pharmacother. 2017 Dec;96:659-666. doi: 10.1016/j.biopha.2017.10.041. Epub 2017 Nov 6.
• [7] Serum thymosin beta4 as a noninvasive biomarker in patients with nonalcoholic steatohepatitis.Rev Esp Enferm Dig. 2018 Jan;110(1):19-24. doi: 10.17235/reed.2017.4690/2016.
• [8] 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.
• [9] 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.