Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIR98RB)

DOT Name	Secretoglobin family 3A member 1 (SCGB3A1)
Synonyms	Cytokine HIN-1; High in normal 1; Pneumo secretory protein 2; PnSP-2; Uteroglobin-related protein 2
Gene Name	SCGB3A1
Related Disease	Asthma ( ) Advanced cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Breast fibrocystic disease ( ) Carcinoma of esophagus ( ) Endometriosis ( ) Esophageal cancer ( ) Familial adenomatous polyposis ( ) Gastric cancer ( ) Influenza ( ) Lung neoplasm ( ) Nasal polyp ( ) Neoplasm ( ) Neoplasm of esophagus ( ) Precancerous condition ( ) Pyropoikilocytosis, hereditary ( ) Small-cell lung cancer ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) Testicular cancer ( ) Triple negative breast cancer ( ) Ductal breast carcinoma in situ ( ) Glioblastoma multiforme ( ) Nasopharyngeal carcinoma ( ) Neuroblastoma ( ) Niemann-Pick disease type C ( ) Breast neoplasm ( ) Lymphoma ( ) Malignant mesothelioma ( ) Non-small-cell lung cancer ( ) Retinoblastoma ( )
UniProt ID	SG3A1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF20490
Sequence	MKLAALLGLCVALSCSSAAAFLVGSAKPVAQPVAALESAAEAGAGTLANPLGTLNPLKLL LSSLGIPVNHLIEGSQKCVAELGPQAVGAVKALKALLGALTVFG
Function	Secreted cytokine-like protein. Inhibits cell growth in vitro.
Tissue Specificity	Highly expressed in lung and prostate . Also found in mammary gland, spleen, pancreas, testis and liver . Detected throughout the airway epithelium in lung, with highest expression in large airways . Found in lung submucosal glands where it localizes to acinar and ductile cells . Not detected in respiratory bronchioles, alveolar ducts or alveolar epithelium . In mammary gland, specifically localizes to luminal epithelial cells .

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Asthma	DISW9QNS	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Breast fibrocystic disease	DISUM7ID	Strong	Biomarker	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Endometriosis	DISX1AG8	Strong	Biomarker	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[8]
Influenza	DIS3PNU3	Strong	Biomarker	[9]
Lung neoplasm	DISVARNB	Strong	Biomarker	[10]
Nasal polyp	DISLP3XE	Strong	Genetic Variation	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
Precancerous condition	DISV06FL	Strong	Altered Expression	[13]
Pyropoikilocytosis, hereditary	DISZGN3B	Strong	Biomarker	[13]
Small-cell lung cancer	DISK3LZD	Strong	Posttranslational Modification	[14]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[15]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[8]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[16]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[12]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Biomarker	[17]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[18]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Posttranslational Modification	[19]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[20]
Niemann-Pick disease type C	DIS492ZO	moderate	Posttranslational Modification	[19]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[21]
Lymphoma	DISN6V4S	Limited	Posttranslational Modification	[22]
Malignant mesothelioma	DISTHJGH	Limited	Posttranslational Modification	[22]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[23]
Retinoblastoma	DISVPNPB	Limited	Posttranslational Modification	[22]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Secretoglobin family 3A member 1 (SCGB3A1).	[24]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Secretoglobin family 3A member 1 (SCGB3A1).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Secretoglobin family 3A member 1 (SCGB3A1).	[27]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Secretoglobin family 3A member 1 (SCGB3A1).	[26]
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References

1	Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population.Braz J Otorhinolaryngol. 2018 Sep-Oct;84(5):599-607. doi: 10.1016/j.bjorl.2017.07.004. Epub 2017 Aug 1.
2	Aberrant promoter methylation of HIN-1 gene may contribute to the pathogenesis of breast cancer: a meta-analysis.Tumour Biol. 2014 Aug;35(8):8209-16. doi: 10.1007/s13277-014-2055-1. Epub 2014 May 22.
3	DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study.Epigenetics. 2016 Sep;11(9):643-652. doi: 10.1080/15592294.2016.1192735. Epub 2016 May 31.
4	Modulation of gene methylation by genistein or lycopene in breast cancer cells.Environ Mol Mutagen. 2008 Jan;49(1):36-45. doi: 10.1002/em.20363.
5	Promoter methylation of HIN-1 in the progression to esophageal squamous cancer.Epigenetics. 2008 Nov;3(6):336-41. doi: 10.4161/epi.3.6.7158. Epub 2008 Nov 8.
6	Molecular evidence for differences in endometrium in severe versus mild endometriosis.Reprod Sci. 2011 Mar;18(3):229-51. doi: 10.1177/1933719110386241. Epub 2010 Nov 9.
7	Relation between normal rectal methylation, smoking status, and the presence or absence of colorectal adenomas.Cancer. 2010 Oct 1;116(19):4495-501. doi: 10.1002/cncr.25348.
8	Silence of HIN-1 expression through methylation of its gene promoter in gastric cancer.World J Gastroenterol. 2011 Jan 28;17(4):526-33. doi: 10.3748/wjg.v17.i4.526.
9	Use of dried clinical samples for storing and detecting influenza RNA.Influenza Other Respir Viruses. 2011 Nov;5(6):413-7. doi: 10.1111/j.1750-2659.2011.00253.x. Epub 2011 Apr 18.
10	Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer.J Transl Med. 2010 Sep 17;8:86. doi: 10.1186/1479-5876-8-86.
11	Investigation of SCGB3A1 (UGRP2) gene arrays in patients with nasal polyposis.Eur Arch Otorhinolaryngol. 2014 Dec;271(12):3209-14. doi: 10.1007/s00405-014-3020-8. Epub 2014 Apr 8.
12	Increased hypermethylation of glutathione S-transferase P1, DNA-binding protein inhibitor, death associated protein kinase and paired box protein-5... Asian Pac J Cancer Prev. 2015;16(2):541-9.
13	Sessile serrated adenomas and classical adenomas: an epigenetic perspective on premalignant neoplastic lesions of the gastrointestinal tract.Int J Cancer. 2011 Oct 15;129(8):1889-98. doi: 10.1002/ijc.25847. Epub 2011 Mar 11.
14	Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types.Mol Cancer Res. 2004 Sep;2(9):489-94.
15	Assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens.Gynecol Oncol. 2010 Jan;116(1):99-104. doi: 10.1016/j.ygyno.2009.09.032.
16	Novel epigenetically deregulated genes in testicular cancer include homeobox genes and SCGB3A1 (HIN-1).J Pathol. 2006 Dec;210(4):441-9. doi: 10.1002/path.2064.
17	Quantitative promoter hypermethylation profiles of ductal carcinoma in situ in North American and Korean women: Potential applications for diagnosis.Cancer Biol Ther. 2008 Sep;7(9):1398-406. doi: 10.4161/cbt.7.9.6425. Epub 2008 Sep 4.
18	HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.Mol Neurobiol. 2016 Apr;53(3):1802-1807. doi: 10.1007/s12035-015-9127-0. Epub 2015 Mar 11.
19	Promoter hypermethylation of high-in-normal 1 gene in primary nasopharyngeal carcinoma.Clin Cancer Res. 2003 Aug 1;9(8):3042-6.
20	Methylation of CASP8, DCR2, and HIN-1 in neuroblastoma is associated with poor outcome.Clin Cancer Res. 2007 Jun 1;13(11):3191-7. doi: 10.1158/1078-0432.CCR-06-2846.
21	Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors.Cancer Biol Ther. 2003 Sep-Oct;2(5):559-63. doi: 10.4161/cbt.2.5.511.
22	Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies.Int J Cancer. 2005 Feb 10;113(4):600-4. doi: 10.1002/ijc.20622.
23	AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer.Tumour Biol. 2012 Apr;33(2):307-14. doi: 10.1007/s13277-011-0266-2. Epub 2011 Nov 19.
24	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.
25	Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
26	Quantification of regional DNA methylation by liquid chromatography/tandem mass spectrometry. Anal Biochem. 2009 Aug 15;391(2):106-13. doi: 10.1016/j.ab.2009.05.012. Epub 2009 May 12.
27	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.