Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZYG2R)

DOT Name Transcription factor ATOH1 (ATOH1)
Synonyms Atonal bHLH transcription factor 1; Class A basic helix-loop-helix protein 14; bHLHa14; Helix-loop-helix protein hATH-1; hATH1; Protein atonal homolog 1
Gene Name ATOH1
Related Disease
Arteriosclerosis ( )
Atherosclerosis ( )
Myocardial infarction ( )
Advanced cancer ( )
Barrett esophagus ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal adenocarcinoma ( )
Gastric cancer ( )
Gastric neoplasm ( )
Hepatocellular carcinoma ( )
Lung carcinoma ( )
Medulloblastoma ( )
Mucinous adenocarcinoma ( )
Neoplasm ( )
Parasitic infection ( )
Respiratory failure ( )
Sensorineural hearing loss disorder ( )
Signet ring cell carcinoma ( )
Stomach cancer ( )
Ulcerative colitis ( )
Adenocarcinoma ( )
Colorectal carcinoma ( )
Hearing loss, autosomal dominant 89 ( )
Lung neoplasm ( )
Neuroendocrine neoplasm ( )
Rheumatoid arthritis ( )
Small-cell lung cancer ( )
UniProt ID
ATOH1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00010
Sequence
MSRLLHAEEWAEVKELGDHHRQPQPHHLPQPPPPPQPPATLQAREHPVYPPELSLLDSTD
PRAWLAPTLQGICTARAAQYLLHSPELGASEAAAPRDEVDGRGELVRRSSGGASSSKSPG
PVKVREQLCKLKGGVVVDELGCSRQRAPSSKQVNGVQKQRRLAANARERRRMHGLNHAFD
QLRNVIPSFNNDKKLSKYETLQMAQIYINALSELLQTPSGGEQPPPPPASCKSDHHHLRT
AASYEGGAGNATAAGAQQASGGSQRPTPPGSCRTRFSAPASAGGYSVQLDALHFSTFEDS
ALTAMMAQKNLSPSLPGSILQPVQEENSKTSPRSHRSDGEFSPHSHYSDSDEAS
Function
Transcriptional regulator. Activates E box-dependent transcription in collaboration with TCF3/E47, but the activity is completely antagonized by the negative regulator of neurogenesis HES1. Plays a role in the differentiation of subsets of neural cells by activating E box-dependent transcription.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arteriosclerosis DISK5QGC Definitive Biomarker [1]
Atherosclerosis DISMN9J3 Definitive Biomarker [1]
Myocardial infarction DIS655KI Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Barrett esophagus DIS416Y7 Strong Altered Expression [3]
Colon cancer DISVC52G Strong Biomarker [4]
Colon carcinoma DISJYKUO Strong Biomarker [4]
Colonic neoplasm DISSZ04P Strong Altered Expression [5]
Colorectal adenocarcinoma DISPQOUB Strong Biomarker [6]
Gastric cancer DISXGOUK Strong Biomarker [7]
Gastric neoplasm DISOKN4Y Strong Altered Expression [8]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [9]
Lung carcinoma DISTR26C Strong Altered Expression [10]
Medulloblastoma DISZD2ZL Strong Biomarker [11]
Mucinous adenocarcinoma DISKNFE8 Strong Biomarker [12]
Neoplasm DISZKGEW Strong Altered Expression [13]
Parasitic infection DISX9CEW Strong Biomarker [14]
Respiratory failure DISVMYJO Strong Biomarker [15]
Sensorineural hearing loss disorder DISJV45Z Strong Biomarker [16]
Signet ring cell carcinoma DISVCUCR Strong Biomarker [12]
Stomach cancer DISKIJSX Strong Biomarker [7]
Ulcerative colitis DIS8K27O Strong Altered Expression [17]
Adenocarcinoma DIS3IHTY Limited Biomarker [18]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [6]
Hearing loss, autosomal dominant 89 DISN52AL Limited Autosomal dominant [19]
Lung neoplasm DISVARNB Limited Altered Expression [18]
Neuroendocrine neoplasm DISNPLOO Limited Altered Expression [18]
Rheumatoid arthritis DISTSB4J Limited Altered Expression [20]
Small-cell lung cancer DISK3LZD Limited Altered Expression [18]
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⏷ Show the Full List of 29 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Transcription factor ATOH1 (ATOH1). [21]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Transcription factor ATOH1 (ATOH1). [22]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Transcription factor ATOH1 (ATOH1). [23]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Transcription factor ATOH1 (ATOH1). [25]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Transcription factor ATOH1 (ATOH1). [26]
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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 ATOH1 (ATOH1). [24]
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References

1 Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility.Nat Genet. 2005 Apr;37(4):365-72. doi: 10.1038/ng1524. Epub 2005 Mar 6.
2 Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.Cancer Res. 2017 Jun 15;77(12):3151-3157. doi: 10.1158/0008-5472.CAN-17-0035. Epub 2017 May 16.
3 Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by inducing the expression of Muc2 and Keratin-20.Dig Dis Sci. 2012 Apr;57(4):845-57. doi: 10.1007/s10620-011-1998-y. Epub 2011 Dec 7.
4 MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by targeting ATOH1.Biochem Biophys Res Commun. 2018 Oct 12;504(4):827-833. doi: 10.1016/j.bbrc.2018.09.054. Epub 2018 Sep 13.
5 Amplified in breast cancer 1 promotes colorectal cancer progression through enhancing notch signaling.Oncogene. 2015 Jul 23;34(30):3935-3945. doi: 10.1038/onc.2014.324. Epub 2014 Sep 29.
6 SCF/c-KIT Signaling Increased Mucin2 Production by Maintaining Atoh1 Expression in Mucinous Colorectal Adenocarcinoma.Int J Mol Sci. 2018 May 22;19(5):1541. doi: 10.3390/ijms19051541.
7 ATOH1 Can Regulate the Tumorigenicity of Gastric Cancer Cells by Inducing the Differentiation of Cancer Stem Cells.PLoS One. 2015 May 7;10(5):e0126085. doi: 10.1371/journal.pone.0126085. eCollection 2015.
8 Hath1 up-regulates gastric mucin gene expression in gastric cells.Biochem Biophys Res Commun. 2006 Jun 16;344(4):1166-71. doi: 10.1016/j.bbrc.2006.03.238. Epub 2006 Apr 21.
9 HBx protein-mediated ATOH1 downregulation suppresses ARID2 expression and promotes hepatocellular carcinoma.Cancer Sci. 2017 Jul;108(7):1328-1337. doi: 10.1111/cas.13277. Epub 2017 Jun 14.
10 Atonal homolog 1 expression in lung cancer correlates with inhibitors of the Wnt pathway as well as the differentiation and primary tumor stage.APMIS. 2013 Feb;121(2):111-9. doi: 10.1111/j.1600-0463.2012.02946.x. Epub 2012 Jul 4.
11 Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation.Dev Cell. 2019 Jan 28;48(2):184-199.e5. doi: 10.1016/j.devcel.2018.12.017.
12 The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein.Biochem Biophys Res Commun. 2013 Mar 1;432(1):175-81. doi: 10.1016/j.bbrc.2013.01.034. Epub 2013 Jan 16.
13 Prognostic relevance of high atonal homolog-1 expression in Merkel cell carcinoma.J Cancer Res Clin Oncol. 2017 Jan;143(1):43-49. doi: 10.1007/s00432-016-2257-6. Epub 2016 Sep 13.
14 Sox4 Promotes Atoh1-Independent Intestinal Secretory Differentiation Toward Tuft and Enteroendocrine Fates.Gastroenterology. 2018 Nov;155(5):1508-1523.e10. doi: 10.1053/j.gastro.2018.07.023. Epub 2018 Jul 25.
15 Atoh1 governs the migration of postmitotic neurons that shape respiratory effectiveness at birth and chemoresponsiveness in adulthood.Neuron. 2012 Sep 6;75(5):799-809. doi: 10.1016/j.neuron.2012.06.027.
16 Update on treatment options for blast-induced hearing loss.Curr Opin Otolaryngol Head Neck Surg. 2019 Oct;27(5):376-380. doi: 10.1097/MOO.0000000000000563.
17 Suppression of hath1 gene expression directly regulated by hes1 via notch signaling is associated with goblet cell depletion in ulcerative colitis.Inflamm Bowel Dis. 2011 Nov;17(11):2251-60. doi: 10.1002/ibd.21611. Epub 2011 Jan 6.
18 Basic helix-loop-helix transcription factor profiling of lung tumors shows aberrant expression of the proneural gene atonal homolog 1 (ATOH1, HATH1, MATH1) in neuroendocrine tumors.Int J Biol Markers. 2007 Apr-Jun;22(2):114-23. doi: 10.1177/172460080702200205.
19 Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1. Clin Genet. 2020 Oct;98(4):353-364. doi: 10.1111/cge.13817. Epub 2020 Aug 24.
20 Gene expression of MASH-1, MATH-1, neuroD and NSCL-2, basic helix-loop-helix proteins, during neural differentiation in P19 embryonal carcinoma cells.Tohoku J Exp Med. 1997 Aug;182(4):327-36. doi: 10.1620/tjem.182.327.
21 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.
22 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.
23 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
24 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.
25 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
26 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.