Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYG47F8)

DOT Name	Desmocollin-3 (DSC3)
Synonyms	Cadherin family member 3; Desmocollin-4; HT-CP
Gene Name	DSC3
Related Disease	Adult glioblastoma ( ) Alopecia ( ) Alzheimer disease ( ) Astrocytoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Colon cancer ( ) Colon carcinoma ( ) Dementia ( ) Ductal carcinoma ( ) Epithelial ovarian cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Hereditary hypotrichosis with recurrent skin vesicles ( ) High blood pressure ( ) Hypotrichosis ( ) Lung cancer ( ) Lung carcinoma ( ) Lung squamous cell carcinoma ( ) Malignant glioma ( ) Metabolic disorder ( ) Moyamoya disease ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pemphigus ( ) Skin disease ( ) Skin neoplasm ( ) Squamous cell carcinoma ( ) Adenocarcinoma ( ) Advanced cancer ( ) Brain neoplasm ( ) Colitis ( ) Colorectal neoplasm ( ) Neuroendocrine cancer ( ) Periodontitis ( ) Prostate cancer ( ) Prostate carcinoma ( ) Small lymphocytic lymphoma ( ) Cerebrovascular disease ( ) Colorectal carcinoma ( ) Hypoglycemia ( ) Neuroblastoma ( ) Osteoarthritis ( ) Type-1/2 diabetes ( )
UniProt ID	DSC3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01049 ; PF00028 ; PF08758
Sequence	MAAAGPRRSVRGAVCLHLLLTLVIFSRAGEACKKVILNVPSKLEADKIIGRVNLEECFRS ADLIRSSDPDFRVLNDGSVYTARAVALSDKKRSFTIWLSDKRKQTQKEVTVLLEHQKKVS KTRHTRETVLRRAKRRWAPIPCSMQENSLGPFPLFLQQVESDAAQNYTVFYSISGRGVDK EPLNLFYIERDTGNLFCTRPVDREEYDVFDLIAYASTADGYSADLPLPLPIRVEDENDNH PVFTEAIYNFEVLESSRPGTTVGVVCATDRDEPDTMHTRLKYSILQQTPRSPGLFSVHPS TGVITTVSHYLDREVVDKYSLIMKVQDMDGQFFGLIGTSTCIITVTDSNDNAPTFRQNAY EAFVEENAFNVEILRIPIEDKDLINTANWRVNFTILKGNENGHFKISTDKETNEGVLSVV KPLNYEENRQVNLEIGVNNEAPFARDIPRVTALNRALVTVHVRDLDEGPECTPAAQYVRI KENLAVGSKINGYKAYDPENRNGNGLRYKKLHDPKGWITIDEISGSIITSKILDREVETP KNELYNITVLAIDKDDRSCTGTLAVNIEDVNDNPPEILQEYVVICKPKMGYTDILAVDPD EPVHGAPFYFSLPNTSPEISRLWSLTKVNDTAARLSYQKNAGFQEYTIPITVKDRAGQAA TKLLRVNLCECTHPTQCRATSRSTGVILGKWAILAILLGIALLFSVLLTLVCGVFGATKG KRFPEDLAQQNLIISNTEAPGDDRVCSANGFMTQTTNNSSQGFCGTMGSGMKNGGQETIE MMKGGNQTLESCRGAGHHHTLDSCRGGHTEVDNCRYTYSEWHSFTQPRLGEKLHRCNQNE DRMPSQDYVLTYNYEGRGSPAGSVGCCSEKQEEDGLDFLNNLEPKFITLAEACTKR
Function	Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.
Tissue Specificity	Epidermis, buccal mucosa, esophagus and cervix.
Reactome Pathway	Formation of the cornified envelope (R-HSA-6809371 ) Keratinization (R-HSA-6805567 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Alopecia	DIS37HU4	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Dementia	DISXL1WY	Strong	Biomarker	[7]
Ductal carcinoma	DIS15EA5	Strong	Altered Expression	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hereditary hypotrichosis with recurrent skin vesicles	DISMD9UB	Strong	Autosomal recessive	[11]
High blood pressure	DISY2OHH	Strong	Biomarker	[3]
Hypotrichosis	DISSW933	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[14]
Malignant glioma	DISFXKOV	Strong	Biomarker	[15]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[16]
Moyamoya disease	DISO62CA	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[9]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[9]
Pemphigus	DISZAZ6M	Strong	Biomarker	[20]
Skin disease	DISDW8R6	Strong	Biomarker	[12]
Skin neoplasm	DIS16DDV	Strong	Altered Expression	[21]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[22]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[23]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[24]
Brain neoplasm	DISY3EKS	moderate	Biomarker	[25]
Colitis	DISAF7DD	moderate	Biomarker	[23]
Colorectal neoplasm	DISR1UCN	moderate	Biomarker	[23]
Neuroendocrine cancer	DISVGJET	moderate	Genetic Variation	[22]
Periodontitis	DISI9JOI	moderate	Biomarker	[26]
Prostate cancer	DISF190Y	moderate	Altered Expression	[27]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[27]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[28]
Cerebrovascular disease	DISAB237	Disputed	Biomarker	[29]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[18]
Hypoglycemia	DISRCKR7	Limited	Genetic Variation	[30]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[31]
Osteoarthritis	DIS05URM	Limited	Altered Expression	[32]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[30]
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⏷ Show the Full List of 47 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Desmocollin-3 (DSC3) affects the response to substance of Doxorubicin.	[43]
NAPQI	DM8F5LR	Investigative	Desmocollin-3 (DSC3) affects the response to substance of NAPQI.	[44]
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7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Desmocollin-3 (DSC3).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Desmocollin-3 (DSC3).	[34]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Desmocollin-3 (DSC3).	[36]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Desmocollin-3 (DSC3).	[37]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Desmocollin-3 (DSC3).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Desmocollin-3 (DSC3).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Desmocollin-3 (DSC3).	[42]
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⏷ Show the Full List of 7 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Desmocollin-3 (DSC3).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Desmocollin-3 (DSC3).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Desmocollin-3 (DSC3).	[41]
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References

1	Permeability measurement using dynamic susceptibility contrast magnetic resonance imaging enhances differential diagnosis of primary central nervous system lymphoma from glioblastoma.Eur Radiol. 2019 Oct;29(10):5539-5548. doi: 10.1007/s00330-019-06097-9. Epub 2019 Mar 15.
2	A novel homozygous variant in the dsp gene underlies the first case of non-syndromic form of alopecia.Arch Dermatol Res. 2015 Nov;307(9):793-801. doi: 10.1007/s00403-015-1590-y. Epub 2015 Jul 7.
3	Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study.Neurobiol Aging. 2017 Feb;50:107-118. doi: 10.1016/j.neurobiolaging.2016.11.004. Epub 2016 Nov 19.
4	Dynamic susceptibility contrast and diffusion MR imaging identify oligodendroglioma as defined by the 2016 WHO classification for brain tumors: histogram analysis approach.Neuroradiology. 2019 May;61(5):545-555. doi: 10.1007/s00234-019-02173-5. Epub 2019 Feb 2.
5	5-Aza-2'-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 2007 Jan 4;26(1):77-90. doi: 10.1038/sj.onc.1209763. Epub 2006 Jun 26.
6	Cell growth inhibition by 3-deoxysappanchalcone is mediated by directly targeting the TOPK signaling pathway in colon cancer.Phytomedicine. 2019 Aug;61:152813. doi: 10.1016/j.phymed.2018.12.036. Epub 2018 Dec 31.
7	A novel DSC approach for evaluating protectant drugs efficacy against dementia.Biochim Biophys Acta Mol Basis Dis. 2017 Nov;1863(11):2934-2941. doi: 10.1016/j.bbadis.2017.07.033. Epub 2017 Aug 1.
8	Epigenetic silencing of DSC3 is a common event in human breast cancer.Breast Cancer Res. 2005;7(5):R669-80. doi: 10.1186/bcr1273. Epub 2005 Jun 16.
9	Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway.Int J Clin Exp Pathol. 2015 Jun 1;8(6):6716-23. eCollection 2015.
10	In Vivo Molecular Profiling of Human Glioma : Cross-Sectional Observational Study Using Dynamic Susceptibility Contrast Magnetic Resonance Perfusion Imaging.Clin Neuroradiol. 2019 Sep;29(3):479-491. doi: 10.1007/s00062-018-0676-2. Epub 2018 Feb 21.
11	A homozygous nonsense mutation in the human desmocollin-3 (DSC3) gene underlies hereditary hypotrichosis and recurrent skin vesicles. Am J Hum Genet. 2009 Oct;85(4):515-20. doi: 10.1016/j.ajhg.2009.08.015. Epub 2009 Sep 17.
12	Desmosomal genodermatoses.Br J Dermatol. 2012 Jan;166(1):36-45. doi: 10.1111/j.1365-2133.2011.10640.x.
13	SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma.J Exp Clin Cancer Res. 2018 May 31;37(1):111. doi: 10.1186/s13046-018-0778-3.
14	The p53 target gene desmocollin 3 acts as a novel tumor suppressor through inhibiting EGFR/ERK pathway in human lung cancer.Carcinogenesis. 2012 Dec;33(12):2326-33. doi: 10.1093/carcin/bgs273. Epub 2012 Aug 31.
15	Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?.AJNR Am J Neuroradiol. 2017 Apr;38(4):685-690. doi: 10.3174/ajnr.A5089. Epub 2017 Feb 16.
16	Changes in metabolic risk factors over 10years and their associations with late-life cognitive performance: The Multi-Ethnic Study of Atherosclerosis.Alzheimers Dement (Amst). 2017 Mar 31;8:18-25. doi: 10.1016/j.dadm.2017.03.003. eCollection 2017.
17	Bayesian Estimation of CBF Measured by DSC-MRI in Patients with Moyamoya Disease: Comparison with (15)O-Gas PET and Singular Value Decomposition.AJNR Am J Neuroradiol. 2019 Nov;40(11):1894-1900. doi: 10.3174/ajnr.A6248. Epub 2019 Oct 10.
18	Desmocollin 3 has a tumor suppressive activity through inhibition of AKT pathway in colorectal cancer.Exp Cell Res. 2019 May 15;378(2):124-130. doi: 10.1016/j.yexcr.2019.03.015. Epub 2019 Mar 8.
19	A randomized trial of TLR-2 agonist CADI-05 targeting desmocollin-3 for advanced non-small-cell lung cancer.Ann Oncol. 2017 Feb 1;28(2):298-304. doi: 10.1093/annonc/mdw608.
20	Nonclassical pemphigus with exclusively IgG anti-desmocollin 3-specific antibodies.Australas J Dermatol. 2019 Aug;60(3):e217-e219. doi: 10.1111/ajd.12991. Epub 2019 Jan 22.
21	Loss of Desmocollin 3 in skin tumor development and progression.Mol Carcinog. 2012 Jul;51(7):535-45. doi: 10.1002/mc.20818. Epub 2011 Jun 16.
22	Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.Appl Immunohistochem Mol Morphol. 2013 Jul;21(4):292-7. doi: 10.1097/PAI.0b013e31826fd4f3.
23	Desmocollin switching in colorectal cancer.Br J Cancer. 2006 Nov 20;95(10):1367-70. doi: 10.1038/sj.bjc.6603453. Epub 2006 Oct 31.
24	Development of a measure for evaluating lesion-wise performance of CAD algorithms in the context of mpMRI detection of prostate cancer.Med Phys. 2018 May;45(5):2076-2088. doi: 10.1002/mp.12861. Epub 2018 Apr 16.
25	Brain DSC MR Perfusion in Children: A Clinical Feasibility Study Using Different Technical Standards of Contrast Administration.AJNR Am J Neuroradiol. 2019 Feb;40(2):359-365. doi: 10.3174/ajnr.A5954. Epub 2019 Jan 17.
26	Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues.J Periodontal Res. 2011 Jun;46(3):345-53. doi: 10.1111/j.1600-0765.2011.01349.x. Epub 2011 Mar 7.
27	Association of DSC3 mRNA down-regulation in prostate cancer with promoter hypermethylation and poor prognosis.PLoS One. 2014 Mar 24;9(3):e92815. doi: 10.1371/journal.pone.0092815. eCollection 2014.
28	Toward personalized therapy for chronic lymphocytic leukemia: DSC and cDNA microarray assessment of two cases.Cancer Biol Ther. 2013 Jan;14(1):6-12. doi: 10.4161/cbt.22623. Epub 2012 Oct 31.
29	Comparison of Blood Oxygenation Level-Dependent fMRI and Provocative DSC Perfusion MR Imaging for Monitoring Cerebrovascular Reserve in Intracranial Chronic Cerebrovascular Disease.AJNR Am J Neuroradiol. 2018 Mar;39(3):448-453. doi: 10.3174/ajnr.A5515. Epub 2018 Jan 25.
30	Does hypoglycaemia affect the improvement in QoL after the transition to insulin in people with type 2 diabetes?.J Endocrinol Invest. 2018 Feb;41(2):249-258. doi: 10.1007/s40618-017-0744-5. Epub 2017 Aug 12.
31	X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism.Hum Mol Genet. 2013 Mar 1;22(5):941-51. doi: 10.1093/hmg/dds499. Epub 2012 Nov 25.
32	Silk fibroin nanoparticles for celecoxib and curcumin delivery: ROS-scavenging and anti-inflammatory activities in an in vitro model of osteoarthritis.Eur J Pharm Biopharm. 2019 Apr;137:37-45. doi: 10.1016/j.ejpb.2019.02.008. Epub 2019 Feb 14.
33	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
34	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
35	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.
36	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
37	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
38	5-Aza-2'-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 2007 Jan 4;26(1):77-90. doi: 10.1038/sj.onc.1209763. Epub 2006 Jun 26.
39	Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
40	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.
41	Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
42	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
43	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
44	Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.