Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DIPWC)

DOT Name Neurogenin-3 (NEUROG3)
Synonyms NGN-3; Class A basic helix-loop-helix protein 7; bHLHa7; Protein atonal homolog 5
Gene Name NEUROG3
Related Disease
Hyperglycemia ( )
Acinar cell carcinoma ( )
Aplasia cutis congenita ( )
Breast cancer ( )
Breast carcinoma ( )
Congenital malabsorptive diarrhea 4 ( )
Constipation ( )
Corpus callosum, agenesis of ( )
Hyperproinsulinemia ( )
Hypogonadotropic hypogonadism ( )
Irritable bowel syndrome ( )
Klinefelter syndrome ( )
Malabsorption syndrome ( )
Multiple endocrine neoplasia type 1 ( )
Neonatal diabetes mellitus ( )
Neoplasm ( )
Obesity ( )
Pancreatic cancer ( )
Permanent neonatal diabetes mellitus ( )
Pituitary adenoma ( )
Superficial epidermolytic ichthyosis ( )
Type-1 diabetes ( )
Primary sclerosing cholangitis ( )
Sclerosing cholangitis ( )
Stroke ( )
UniProt ID
NGN3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00010
Sequence
MTPQPSGAPTVQVTRETERSFPRASEDEVTCPTSAPPSPTRTRGNCAEAEEGGCRGAPRK
LRARRGGRSRPKSELALSKQRRSRRKKANDRERNRMHNLNSALDALRGVLPTFPDDAKLT
KIETLRFAHNYIWALTQTLRIADHSLYALEPPAPHCGELGSPGGSPGDWGSLYSPVSQAG
SLSPAASLEERPGLLGATFSACLSPGSLAFSDFL
Function
Acts as a transcriptional regulator. Together with NKX2-2, initiates transcriptional activation of NEUROD1. Involved in neurogenesis. Also required for the specification of a common precursor of the 4 pancreatic endocrine cell types.
KEGG Pathway
Maturity onset diabetes of the young (hsa04950 )
Reactome Pathway
Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells (R-HSA-210746 )
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744 )

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hyperglycemia DIS0BZB5 Definitive Biomarker [1]
Acinar cell carcinoma DIS37Y0J Strong Biomarker [2]
Aplasia cutis congenita DISMDAYM Strong Genetic Variation [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Congenital malabsorptive diarrhea 4 DISSYAAF Strong Autosomal recessive [4]
Constipation DISRQXWI Strong Biomarker [5]
Corpus callosum, agenesis of DISO9P40 Strong Genetic Variation [2]
Hyperproinsulinemia DISSQ05S Strong Genetic Variation [6]
Hypogonadotropic hypogonadism DIS8JSKR Strong Biomarker [7]
Irritable bowel syndrome DIS27206 Strong Biomarker [8]
Klinefelter syndrome DISOUI7W Strong Biomarker [7]
Malabsorption syndrome DISGMUVS Strong Altered Expression [9]
Multiple endocrine neoplasia type 1 DIS0RJRK Strong Altered Expression [10]
Neonatal diabetes mellitus DISFHF9K Strong Genetic Variation [11]
Neoplasm DISZKGEW Strong Genetic Variation [12]
Obesity DIS47Y1K Strong Biomarker [13]
Pancreatic cancer DISJC981 Strong Genetic Variation [14]
Permanent neonatal diabetes mellitus DIS5AEXS Strong Autosomal recessive [4]
Pituitary adenoma DISJ5R1X Strong Genetic Variation [15]
Superficial epidermolytic ichthyosis DISWX6O4 Strong Biomarker [8]
Type-1 diabetes DIS7HLUB Strong Genetic Variation [9]
Primary sclerosing cholangitis DISTH5WJ Limited Altered Expression [16]
Sclerosing cholangitis DIS7GZNB Limited Biomarker [16]
Stroke DISX6UHX Limited Biomarker [17]
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⏷ Show the Full List of 25 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Neurogenin-3 (NEUROG3). [18]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Neurogenin-3 (NEUROG3). [19]
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References

1 Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors.EBioMedicine. 2018 Oct;36:358-366. doi: 10.1016/j.ebiom.2018.09.035. Epub 2018 Sep 25.
2 Prevention of pancreatic acinar cell carcinoma by Roux-en-Y Gastric Bypass Surgery.Nat Commun. 2018 Oct 10;9(1):4183. doi: 10.1038/s41467-018-06571-w.
3 ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3.Oncotarget. 2017 Apr 13;8(33):54388-54401. doi: 10.18632/oncotarget.17077. eCollection 2017 Aug 15.
4 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
5 Abnormalities in ileal stem, neurogenin 3, and enteroendocrine cells in patients with irritable bowel syndrome.BMC Gastroenterol. 2017 Aug 1;17(1):90. doi: 10.1186/s12876-017-0643-4.
6 Genetic variation of Neurogenin 3 is slightly associated with hyperproinsulinaemia and progression toward type 2 diabetes.Exp Clin Endocrinol Diabetes. 2008 Mar;116(3):178-83. doi: 10.1055/s-2007-992156. Epub 2007 Oct 12.
7 Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency.J Clin Endocrinol Metab. 2016 Oct;101(10):3555-3558. doi: 10.1210/jc.2016-2319. Epub 2016 Aug 17.
8 Enteroendocrine, Musashi 1 and neurogenin 3 cells in the large intestine of Thai and Norwegian patients with irritable bowel syndrome.Scand J Gastroenterol. 2017 Dec;52(12):1331-1339. doi: 10.1080/00365521.2017.1371793. Epub 2017 Aug 30.
9 Null mutations of NEUROG3 are associated with delayed-onset diabetes mellitus.JCI Insight. 2020 Jan 16;5(1):e127657. doi: 10.1172/jci.insight.127657.
10 Neurogenin 3 and neurogenic differentiation 1 are retained in the cytoplasm of multiple endocrine neoplasia type 1 islet and pancreatic endocrine tumor cells.Pancreas. 2009 Apr;38(3):259-66. doi: 10.1097/MPA.0b013e3181930818.
11 A novel NEUROG3 mutation in neonatal diabetes associated with a neuro-intestinal syndrome.Pediatr Diabetes. 2018 May;19(3):381-387. doi: 10.1111/pedi.12576. Epub 2017 Sep 22.
12 Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors.Mol Cell Biol. 2015 Oct;35(19):3274-83. doi: 10.1128/MCB.00302-15. Epub 2015 Jul 13.
13 Developmental programming of appetite/satiety.Ann Nutr Metab. 2014;64 Suppl 1:36-44. doi: 10.1159/000360508. Epub 2014 Jul 23.
14 Neurogenin 3-directed cre deletion of Tsc1 gene causes pancreatic acinar carcinoma.Neoplasia. 2014 Nov 20;16(11):909-17. doi: 10.1016/j.neo.2014.08.010. eCollection 2014 Nov.
15 Differential expression of neurogenins and NeuroD1 in human pituitary tumours.J Endocrinol. 2007 Sep;194(3):475-84. doi: 10.1677/JOE-07-0020.
16 Activation of the developmental pathway neurogenin-3/microRNA-7a regulates cholangiocyte proliferation in response to injury.Hepatology. 2014 Oct;60(4):1324-35. doi: 10.1002/hep.27262. Epub 2014 Aug 25.
17 Novel susceptibility genes were found in a targeted sequencing of stroke patients with or without depression in the Chinese Han population.J Affect Disord. 2019 Aug 1;255:1-9. doi: 10.1016/j.jad.2019.05.023. Epub 2019 May 13.
18 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.
19 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.