Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXN5B9R)

• DOT Name: Helix-loop-helix protein 1 (NHLH1)
• Synonyms: HEN-1; Class A basic helix-loop-helix protein 35; bHLHa35; Nescient helix loop helix 1; NSCL-1
• Gene Name: NHLH1
• Related Disease:
  Adenocarcinoma
  Cleft lip/palate
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Non-small-cell lung cancer
  Tooth agenesis
  Advanced cancer
  Cleft palate
  Isolated cleft palate
  Neuroblastoma
  Popliteal pterygium syndrome
  T-cell acute lymphoblastic leukaemia
  Van der Woude syndrome
• UniProt ID: HEN1_HUMAN
• Pfam ID: PF00010
• Sequence:
  MMLNSDTMELDLPPTHSETESGFSDCGGGAGPDGAGPGGPGGGQARGPEPGEPGRKDLQH
  LSREERRRRRRATAKYRTAHATRERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLA
  ICYISYLNHVLDV
• Function: May serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Cleft lip/palate	DIS14IG3	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Tooth agenesis	DIS1PWC7	Strong	Genetic Variation	[6]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[7]
Cleft palate	DIS6G5TF	Limited	Genetic Variation	[8]
Isolated cleft palate	DISV80CD	Limited	Genetic Variation	[8]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[9]
Popliteal pterygium syndrome	DISRS4H8	Limited	Genetic Variation	[10]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[9]
Van der Woude syndrome	DISADZS1	Limited	Biomarker	[10]

3 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 Helix-loop-helix protein 1 (NHLH1).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Helix-loop-helix protein 1 (NHLH1).	[12]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Helix-loop-helix protein 1 (NHLH1).	[15]

2 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 Helix-loop-helix protein 1 (NHLH1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Helix-loop-helix protein 1 (NHLH1).	[14]

References

• [1] LOH at the APC/MCC gene (5Q21) is frequent in early stages of non-small cell lung cancer.Pathol Res Pract. 1999;195(10):677-80. doi: 10.1016/S0344-0338(99)80058-2.
• [2] The impact of nonsyndromic cleft lip with or without cleft palate on oral health-related quality of life.J Appl Oral Sci. 2018 Apr 5;26:e20170145. doi: 10.1590/1678-7757-2017-0145.
• [3] Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate.Oral Dis. 2018 Sep;24(6):1068-1072. doi: 10.1111/odi.12879. Epub 2018 Jun 8.
• [4] An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma.Neoplasia. 2008 Jan;10(1):89-98. doi: 10.1593/neo.07891.
• [5] Micronodules Detected on Computed Tomography During the National Lung Screening Trial: Prevalence and Relation to Positive Studies and Lung Cancer.J Thorac Oncol. 2019 Sep;14(9):1538-1546. doi: 10.1016/j.jtho.2019.05.045. Epub 2019 Jul 8.
• [6] Familial non-syndromic cleft lip and palate--analysis of the IRF6 gene and clinical phenotypes.Eur J Orthod. 2008 Apr;30(2):169-75. doi: 10.1093/ejo/cjm097. Epub 2008 Jan 21.
• [7] Gene expression profiling analysis contributes to understanding the association between non-syndromic cleft lip and palate, and cancer.Mol Med Rep. 2016 Mar;13(3):2110-6. doi: 10.3892/mmr.2016.4802. Epub 2016 Jan 20.
• [8] Association of the WNT3 polymorphisms and non-syndromic cleft lip with or without cleft palate: evidence from a meta-analysis.Biosci Rep. 2018 Nov 23;38(6):BSR20181676. doi: 10.1042/BSR20181676. Print 2018 Dec 21.
• [9] HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma.Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8492-6. doi: 10.1073/pnas.89.18.8492.
• [10] Association and Mutation Analyses of the IRF6 Gene in Families With Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate.Cleft Palate Craniofac J. 2014 Jan;51(1):49-55. doi: 10.1597/11-220. Epub 2013 Feb 8.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] 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.
• [15] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.