Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMJZP9G)

• DOT Name: Neurogenin-1 (NEUROG1)
• Synonyms: NGN-1; Class A basic helix-loop-helix protein 6; bHLHa6; Neurogenic basic-helix-loop-helix protein; Neurogenic differentiation factor 3; NeuroD3
• Gene Name: NEUROG1
• Related Disease:
  Adenoma
  Advanced cancer
  Autism
  Glomerulonephritis
  Intrahepatic cholangiocarcinoma
  Leiomyoma
  Medulloblastoma
  Metastatic malignant neoplasm
  Neoplasm
  Pituitary adenoma
  Primitive neuroectodermal tumor
  Retinoblastoma
  Uterine fibroids
  Hearing loss, autosomal recessive
  Mobius syndrome
  Neuroblastoma
  Schizoaffective disorder
  Sensorineural hearing loss disorder
  Kaposi sarcoma
  Amyotrophic lateral sclerosis
  Colorectal carcinoma
  Pancreatic cancer
  Schizophrenia
• UniProt ID: NGN1_HUMAN
• Pfam ID: PF00010
• Sequence:
  MPARLETCISDLDCASSSGSDLSGFLTDEEDCARLQQAASASGPPAPARRGAPNISRASE
  VPGAQDDEQERRRRRGRTRVRSEALLHSLRRSRRVKANDRERNRMHNLNAALDALRSVLP
  SFPDDTKLTKIETLRFAYNYIWALAETLRLADQGLPGGGARERLLPPQCVPCLPGPPSPA
  SDAESWGSGAAAASPLSDPSSPAASEDFTYRPGDPVFSFPSLPKDLLHTTPCFIPYH
• Function: Acts as a transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis.
• Tissue Specificity: Expression restricted to the embryonic nervous system.
• KEGG Pathway: Sig.ling pathways regulating pluripotency of stem cells (hsa04550)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Biomarker	[3]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[4]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[5]
Leiomyoma	DISLDDFN	Strong	Biomarker	[6]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Pituitary adenoma	DISJ5R1X	Strong	Altered Expression	[10]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[8]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[11]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[6]
Hearing loss, autosomal recessive	DIS8G9R9	moderate	Genetic Variation	[12]
Mobius syndrome	DIS9YXP5	moderate	Genetic Variation	[12]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[13]
Schizoaffective disorder	DISLBW6B	moderate	Biomarker	[14]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Biomarker	[15]
Kaposi sarcoma	DISC1H1Z	Disputed	Genetic Variation	[16]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[17]
Colorectal carcinoma	DIS5PYL0	Limited	Posttranslational Modification	[18]
Pancreatic cancer	DISJC981	Limited	Biomarker	[19]
Schizophrenia	DISSRV2N	Limited	Biomarker	[14]

6 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 Neurogenin-1 (NEUROG1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neurogenin-1 (NEUROG1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neurogenin-1 (NEUROG1).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of Neurogenin-1 (NEUROG1).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Neurogenin-1 (NEUROG1).	[25]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Neurogenin-1 (NEUROG1).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Neurogenin-1 (NEUROG1).	[21]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Neurogenin-1 (NEUROG1).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neurogenin-1 (NEUROG1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Neurogenin-1 (NEUROG1).	[27]

References

• [1] Epigenetic profiling of synchronous colorectal neoplasias by quantitative DNA methylation analysis.Mod Pathol. 2006 Aug;19(8):1083-90. doi: 10.1038/modpathol.3800618. Epub 2006 May 12.
• [2] Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1 identifies a subgroup of medulloblastomas not expressing ATOH1.Neuro Oncol. 2007 Jul;9(3):298-307. doi: 10.1215/15228517-2007-014. Epub 2007 May 23.
• [3] Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis.BMC Med Genet. 2007 Dec 6;8:74. doi: 10.1186/1471-2350-8-74.
• [4] Small Red Blood Cell Fraction on the UF-1000i Urine Analyzer as a Screening Tool to Detect Dysmorphic Red Blood Cells for Diagnosing Glomerulonephritis.Ann Lab Med. 2019 May;39(3):271-277. doi: 10.3343/alm.2019.39.3.271.
• [5] Methylation profiles of multiple CpG island loci in extrahepatic cholangiocarcinoma versus those of intrahepatic cholangiocarcinomas.Arch Pathol Lab Med. 2007 Jun;131(6):923-30. doi: 10.5858/2007-131-923-MPOMCI.
• [6] Selective progesterone receptor modulators for fertility preservation in women with symptomatic uterine fibroids.Biol Reprod. 2017 Sep 1;97(3):337-352. doi: 10.1093/biolre/iox094.
• [7] RalA is overactivated in medulloblastoma.J Neurooncol. 2016 Oct;130(1):99-110. doi: 10.1007/s11060-016-2236-4. Epub 2016 Aug 26.
• [8] Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors.Cancer Res. 1997 Aug 15;57(16):3526-31.
• [9] Methylation of NEUROG1 in serum is a sensitive marker for the detection of early colorectal cancer.Am J Gastroenterol. 2011 Jun;106(6):1110-8. doi: 10.1038/ajg.2011.6. Epub 2011 Feb 15.
• [10] Differential expression of neurogenins and NeuroD1 in human pituitary tumours.J Endocrinol. 2007 Sep;194(3):475-84. doi: 10.1677/JOE-07-0020.
• [11] Hypermethylation of CpG island loci of multiple tumor suppressor genes in retinoblastoma.Exp Eye Res. 2008 Feb;86(2):201-6. doi: 10.1016/j.exer.2007.10.010. Epub 2007 Nov 4.
• [12] A boy with homozygous microdeletion of NEUROG1 presents with a congenital cranial dysinnervation disorder [Moebius syndrome variant].Behav Brain Funct. 2013 Feb 18;9:7. doi: 10.1186/1744-9081-9-7.
• [13] Overexpression of neurogenin1 induces neurite outgrowth in F11 neuroblastoma cells.Exp Mol Med. 2002 Dec 31;34(6):469-75. doi: 10.1038/emm.2002.65.
• [14] Basic helix-loop-helix transcription factor NEUROG1 and schizophrenia: effects on illness susceptibility, MRI brain morphometry and cognitive abilities.Schizophr Res. 2008 Dec;106(2-3):192-9. doi: 10.1016/j.schres.2008.08.009. Epub 2008 Sep 16.
• [15] The role of transcription factors of neurosensory cells in non-syndromic sensorineural hearing loss with or without inner ear malformation.Acta Otolaryngol. 2016;136(3):277-82. doi: 10.3109/00016489.2015.1109706. Epub 2015 Dec 4.
• [16] Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype.Tumour Biol. 2011 Aug;32(4):653-9. doi: 10.1007/s13277-011-0165-6. Epub 2011 Apr 6.
• [17] Neural induction with neurogenin 1 enhances the therapeutic potential of mesenchymal stem cells in an amyotrophic lateral sclerosis mouse model.Cell Transplant. 2013;22(5):855-70. doi: 10.3727/096368912X637019.
• [18] Methylation and microsatellite status and recurrence following adjuvant FOLFOX in colorectal cancer.Int J Cancer. 2013 May 1;132(9):2209-16. doi: 10.1002/ijc.27888. Epub 2012 Oct 29.
• [19] Novel Synergistic Combination of Mitotic Arrest and Promotion of Apoptosis for Treatment of Pancreatic Adenocarcinoma.Transl Oncol. 2019 Apr;12(4):683-692. doi: 10.1016/j.tranon.2019.01.009. Epub 2019 Mar 4.
• [20] Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol. Toxicol In Vitro. 2015 Apr;29(3):449-57. doi: 10.1016/j.tiv.2014.12.001. Epub 2014 Dec 15.
• [21] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [22] Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing. Toxicology. 2008 Jul 30;249(2-3):243-50. doi: 10.1016/j.tox.2008.05.014. Epub 2008 Jul 2.
• [23] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [24] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [25] Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect. 2015 Jan;123(1):80-7. doi: 10.1289/ehp.1408437. Epub 2014 Aug 19.
• [26] 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.
• [27] 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.
• [28] Characterization of paraquat-induced miRNA profiling response in hNPCs undergoing proliferation. Int J Mol Sci. 2014 Oct 13;15(10):18422-36. doi: 10.3390/ijms151018422.