Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYYE1GK)

• DOT Name: Mucin-20 (MUC20)
• Synonyms: MUC-20
• Gene Name: MUC20
• Related Disease:
  Endometrial cancer
  Endometrial carcinoma
  Esophageal squamous cell carcinoma
  Cystic fibrosis
  Epithelial neoplasm
  Epithelial ovarian cancer
  IgA nephropathy
  Immunodeficiency
  Laryngitis
  Lupus nephritis
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic ductal carcinoma
  Ulcerative colitis
• UniProt ID: MUC20_HUMAN
• Sequence:
  MGCLWGLALPLFFFCWEVGVSGSSAGPSTRRADTAMTTDDTEVPAMTLAPGHAALETQTL
  SAETSSRASTPAGPIPEAETRGAKRISPARETRSFTKTSPNFMVLIATSVETSAASGSPE
  GAGMTTVQTITGSDPREAIFDTLCTDDSSEEAKTLTMDILTLAHTSTEAKGLSSESSASS
  DSPHPVITPSRASESSASSDGPHPVITPSRASESSASSDGPHPVITPSRASESSASSDGP
  HPVITPSRASESSASSDGPHPVITPSRASESSASSDGPHPVITPSRASESSASSDGPHPV
  ITPSRASESSASSDGPHPVITPSRASESSASSDGPHPVITPSRASESSASSDGLHPVITP
  SRASESSASSDGPHPVITPSRASESSASSDGPHPVITPSWSPGSDVTLLAEALVTVTNIE
  VINCSITEIETTTSSIPGASDTDLIPTEGVKASSTSDPPALPDSTEAKPHITEVTASAET
  LSTAGTTESAAPDATVGTPLPTNSATEREVTAPGATTLSGALVTVSRNPLEETSALSVET
  PSYVKVSGAAPVSIEAGSAVGKTTSFAGSSASSYSPSEAALKNFTPSETPTMDIATKGPF
  PTSRDPLPSVPPTTTNSSRGTNSTLAKITTSAKTTMKPPTATPTTARTRPTTDVSAGENG
  GFLLLRLSVASPEDLTDPRVAERLMQQLHRELHAHAPHFQVSLLRVRRG
• Function: May regulate MET signaling cascade. Seems to decrease hepatocyte growth factor (HGF)-induced transient MAPK activation. Blocks GRB2 recruitment to MET thus suppressing the GRB2-RAS pathway. Inhibits HGF-induced proliferation of MMP1 and MMP9 expression.
• Tissue Specificity: Highly expressed in kidney, moderately in placenta, lung, prostate, liver, and digestive system. In the kidney, localized in the proximal tubules but not in the glomerulus or distal tubules. Detected in most of the male urogenital tract epithelia, with the exception of epididymis.
• Reactome Pathway:
  Defective C1GALT1C1 causes TNPS (R-HSA-5083632)
  Defective GALNT12 causes CRCS1 (R-HSA-5083636)
  Dectin-2 family (R-HSA-5621480)
  MET activates RAS signaling (R-HSA-8851805)
  O-linked glycosylation of mucins (R-HSA-913709)
  Termination of O-glycan biosynthesis (R-HSA-977068)
  Defective GALNT3 causes HFTC (R-HSA-5083625)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial cancer	DISW0LMR	Definitive	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Definitive	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[2]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[3]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[6]
Immunodeficiency	DIS093I0	Strong	Biomarker	[7]
Laryngitis	DISX7UUD	Strong	Altered Expression	[8]
Lupus nephritis	DISCVGPZ	Strong	Altered Expression	[9]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Biomarker	[7]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[10]

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 Mucin-20 (MUC20).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mucin-20 (MUC20).	[19]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mucin-20 (MUC20).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Mucin-20 (MUC20).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mucin-20 (MUC20).	[14]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Mucin-20 (MUC20).	[15]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Mucin-20 (MUC20).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Mucin-20 (MUC20).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Mucin-20 (MUC20).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mucin-20 (MUC20).	[20]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the expression of Mucin-20 (MUC20).	[21]

References

• [1] High expression of MUC20 drives tumorigenesis and predicts poor survival in endometrial cancer.J Cell Biochem. 2019 Jul;120(7):11859-11866. doi: 10.1002/jcb.28466. Epub 2019 Feb 19.
• [2] Possible prediction of the response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy based on gene expression profiling.Oncotarget. 2016 Jan 26;7(4):4531-41. doi: 10.18632/oncotarget.6554.
• [3] Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nat Commun. 2015 Sep 29;6:8382. doi: 10.1038/ncomms9382.
• [4] The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma.J Cancer Res Ther. 2015 Aug;11 Suppl 1:C74-9. doi: 10.4103/0973-1482.163846.
• [5] MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin 1 pathway.Gynecol Oncol. 2016 Jan;140(1):131-7. doi: 10.1016/j.ygyno.2015.11.025. Epub 2015 Nov 23.
• [6] Tandem repeats polymorphism of MUC20 is an independent factor for the progression of immunoglobulin A nephropathy.Am J Nephrol. 2006;26(1):43-9. doi: 10.1159/000091785. Epub 2006 Feb 24.
• [7] Silencing of MUC20 suppresses the malignant character of pancreatic ductal adenocarcinoma cells through inhibition of the HGF/MET pathway.Oncogene. 2018 Nov;37(46):6041-6053. doi: 10.1038/s41388-018-0403-0. Epub 2018 Jul 11.
• [8] Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux.Ann Otol Rhinol Laryngol. 2008 Sep;117(9):688-95. doi: 10.1177/000348940811700911.
• [9] Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney.J Biol Chem. 2004 Jan 16;279(3):1968-79. doi: 10.1074/jbc.M304558200. Epub 2003 Oct 17.
• [10] Differential Expression of MUC12, MUC16, and MUC20 in Patients with Active and Remission Ulcerative Colitis.Mediators Inflamm. 2015;2015:659018. doi: 10.1155/2015/659018. Epub 2015 Dec 6.
• [11] 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.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [14] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [15] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [19] 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.
• [20] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [21] Cordycepin inhibits the proliferation and progression of NPC by targeting the MAPK/ERK and -catenin pathways. Oncol Lett. 2022 Jan;23(1):20. doi: 10.3892/ol.2021.13138. Epub 2021 Nov 16.