Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT11HC3A)

• DOT Name: Desmoglein-1 (DSG1)
• Synonyms: Cadherin family member 4; Desmosomal glycoprotein 1; DG1; DGI; Pemphigus foliaceus antigen
• Gene Name: DSG1
• Related Disease:
  Oral lichen planus
  Severe dermatitis-multiple allergies-metabolic wasting syndrome
  Advanced cancer
  Allergy
  Alzheimer disease
  Bullous pemphigoid
  Carcinoma of esophagus
  Cardiomyopathy
  Crohn disease
  Dentinogenesis imperfecta
  Eosinophilic esophagitis
  Exanthem
  Hereditary diffuse gastric adenocarcinoma
  Impetigo
  Melanoma
  Metabolic disorder
  Palmoplantar keratoderma i, striate, focal, or diffuse
  Pemphigus
  Skin disease
  Squamous cell carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Palmoplantar keratosis
  Periodontitis
  Diffuse palmoplantar keratoderma with painful fissures
  Focal palmoplantar keratoderma with joint keratoses
  Striate palmoplantar keratoderma
  Allodynia
  Atopic dermatitis
  Exfoliative dermatitis
• UniProt ID: DSG1_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MDWSFFRVVAMLFIFLVVVEVNSEFRIQVRDYNTKNGTIKWHSIRRQKREWIKFAAACRE
  GEDNSKRNPIAKIHSDCAANQQVTYRISGVGIDQPPYGIFVINQKTGEINITSIVDREVT
  PFFIIYCRALNSMGQDLERPLELRVRVLDINDNPPVFSMATFAGQIEENSNANTLVMILN
  ATDADEPNNLNSKIAFKIIRQEPSDSPMFIINRNTGEIRTMNNFLDREQYGQYALAVRGS
  DRDGGADGMSAECECNIKILDVNDNIPYMEQSSYTIEIQENTLNSNLLEIRVIDLDEEFS
  ANWMAVIFFISGNEGNWFEIEMNERTNVGILKVVKPLDYEAMQSLQLSIGVRNKAEFHHS
  IMSQYKLKASAISVTVLNVIEGPVFRPGSKTYVVTGNMGSNDKVGDFVATDLDTGRPSTT
  VRYVMGNNPADLLAVDSRTGKLTLKNKVTKEQYNMLGGKYQGTILSIDDNLQRTCTGTIN
  INIQSFGNDDRTNTEPNTKITTNTGRQESTSSTNYDTSTTSTDSSQVYSSEPGNGAKDLL
  SDNVHFGPAGIGLLIMGFLVLGLVPFLMICCDCGGAPRSAAGFEPVPECSDGAIHSWAVE
  GPQPEPRDITTVIPQIPPDNANIIECIDNSGVYTNEYGGREMQDLGGGERMTGFELTEGV
  KTSGMPEICQEYSGTLRRNSMRECREGGLNMNFMESYFCQKAYAYADEDEGRPSNDCLLI
  YDIEGVGSPAGSVGCCSFIGEDLDDSFLDTLGPKFKKLADISLGKESYPDLDPSWPPQST
  EPVCLPQETEPVVSGHPPISPHFGTTTVISESTYPSGPGVLHPKPILDPLGYGNVTVTES
  YTTSDTLKPSVHVHDNRPASNVVVTERVVGPISGADLHGMLEMPDLRDGSNVIVTERVIA
  PSSSLPTSLTIHHPRESSNVVVTERVIQPTSGMIGSLSMHPELANAHNVIVTERVVSGAG
  VTGISGTTGISGGIGSSGLVGTSMGAGSGALSGAGISGGGIGLSSLGGTASIGHMRSSSD
  HHFNQTIGSASPSTARSRITKYSTVQYSK
• Function: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
• Tissue Specificity: Epidermis, tongue, tonsil and esophagus.
• KEGG Pathway: Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Keratinization (R-HSA-6805567)
  Formation of the cornified envelope (R-HSA-6809371)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  Apoptotic cleavage of cell adhesion proteins (R-HSA-351906)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral lichen planus	DISVEAJA	Definitive	Altered Expression	[1]
Severe dermatitis-multiple allergies-metabolic wasting syndrome	DIS1TEJB	Definitive	Autosomal dominant	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Allergy	DIS48ZAP	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bullous pemphigoid	DISOJLKV	Strong	Biomarker	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[7]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[8]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[9]
Dentinogenesis imperfecta	DISJLZU4	Strong	Genetic Variation	[10]
Eosinophilic esophagitis	DISR8WSB	Strong	Altered Expression	[11]
Exanthem	DISAFOQN	Strong	Biomarker	[12]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[13]
Impetigo	DISOF023	Strong	Biomarker	[14]
Melanoma	DIS1RRCY	Strong	Biomarker	[15]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[4]
Palmoplantar keratoderma i, striate, focal, or diffuse	DISZ0T7D	Strong	Autosomal dominant	[2]
Pemphigus	DISZAZ6M	Strong	Biomarker	[16]
Skin disease	DISDW8R6	Strong	Biomarker	[17]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[18]
Head and neck cancer	DISBPSQZ	moderate	Biomarker	[19]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[19]
Palmoplantar keratosis	DISYQGFB	moderate	Genetic Variation	[20]
Periodontitis	DISI9JOI	moderate	Altered Expression	[21]
Diffuse palmoplantar keratoderma with painful fissures	DISYII8V	Supportive	Autosomal dominant	[22]
Focal palmoplantar keratoderma with joint keratoses	DIS0JR60	Supportive	Autosomal dominant	[23]
Striate palmoplantar keratoderma	DISLGEYP	Supportive	Autosomal dominant	[24]
Allodynia	DISQFDGF	Limited	Biomarker	[25]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[26]
Exfoliative dermatitis	DISQEWIW	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Desmoglein-1 (DSG1).	[27]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Desmoglein-1 (DSG1).	[29]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Desmoglein-1 (DSG1).	[30]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Desmoglein-1 (DSG1).	[31]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Desmoglein-1 (DSG1).	[32]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Desmoglein-1 (DSG1).	[33]

2 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 Desmoglein-1 (DSG1).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Desmoglein-1 (DSG1).	[34]

References

• [1] Phenotypic alteration of basal cells in oral lichen planus; switching keratin 19 and desmoglein 1 expression.J Oral Sci. 2018 Dec 27;60(4):507-513. doi: 10.2334/josnusd.17-0396. Epub 2018 Aug 25.
• [2] 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.
• [3] Desmoglein 1 Regulates Invadopodia by Suppressing EGFR/Erk Signaling in an Erbin-Dependent Manner.Mol Cancer Res. 2019 May;17(5):1195-1206. doi: 10.1158/1541-7786.MCR-18-0048. Epub 2019 Jan 17.
• [4] Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet. 2013 Oct;45(10):1244-1248. doi: 10.1038/ng.2739. Epub 2013 Aug 25.
• [5] Insights from modeling the tertiary structure of human BACE2.J Proteome Res. 2004 Sep-Oct;3(5):1069-72. doi: 10.1021/pr049905s.
• [6] Accuracy of molecular diagnostics in pemphigus and bullous pemphigoid: comparison of commercial and modified mosaic indirect immunofluorescence tests as well as enzyme-linked immunosorbent assays.Postepy Dermatol Alergol. 2017 Feb;34(1):21-27. doi: 10.5114/ada.2017.65617. Epub 2017 Feb 7.
• [7] Biological properties of biopsy specimens are useful for predicting lymph node micrometastasis in esophageal carcinoma.Anticancer Res. 2002 Sep-Oct;22(5):2951-6.
• [8] Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions.Acta Derm Venereol. 2019 Jul 1;99(9):789-796. doi: 10.2340/00015555-3203.
• [9] Serological Epithelial Component Proteins Identify Intestinal Complications in Crohn's Disease.Mol Cell Proteomics. 2017 Jul;16(7):1244-1257. doi: 10.1074/mcp.M116.066506. Epub 2017 May 10.
• [10] A novel DSPP mutation causes dentinogenesis imperfecta type II in a large Mongolian family.BMC Med Genet. 2010 Feb 10;11:23. doi: 10.1186/1471-2350-11-23.
• [11] Impedance and Histologic Characteristics of the Sub-Laryngeal Esophagus Distinguish Eosinophilic Esophagitis From Other Esophageal Disorders.Clin Gastroenterol Hepatol. 2020 Jul;18(8):1727-1735.e2. doi: 10.1016/j.cgh.2019.09.032. Epub 2019 Oct 4.
• [12] Desmoglein1 Deficiency Is a Potential Cause of Cutaneous Eruptions Induced by Shuanghuanglian Injection.Molecules. 2018 Jun 19;23(6):1477. doi: 10.3390/molecules23061477.
• [13] The human gene (DSG3) coding for the pemphigus vulgaris antigen is, like the genes coding for the other two known desmogleins, assigned to chromosome 18.Hum Genet. 1992 May;89(3):347-50. doi: 10.1007/BF00220557.
• [14] Production of recombinant extracellular domains of canine desmoglein 1 (Dsg1) by baculovirus expression.Vet Immunol Immunopathol. 2003 Oct 15;95(3-4):177-82. doi: 10.1016/s0165-2427(03)00107-7.
• [15] Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development.Oncogene. 2001 Dec 6;20(56):8125-35. doi: 10.1038/sj.onc.1205034.
• [16] Endocytosis of IgG, Desmoglein 1, and Plakoglobin in Pemphigus Foliaceus Patient Skin.Front Immunol. 2019 Nov 12;10:2635. doi: 10.3389/fimmu.2019.02635. eCollection 2019.
• [17] Salivary Samples for the Diagnosis of Pemphigus vulgaris Using the BIOCHIP Approach: a Pilot Study.In Vivo. 2017 Jan 2;31(1):97-99. doi: 10.21873/invivo.11030.
• [18] Kallikrein-5 promotes cleavage of desmoglein-1 and loss of cell-cell cohesion in oral squamous cell carcinoma.J Biol Chem. 2011 Mar 18;286(11):9127-35. doi: 10.1074/jbc.M110.191361. Epub 2010 Dec 16.
• [19] Analysis of gene coexpression network reveals prognostic significance of CNFN in patients with head and neck cancer.Oncol Rep. 2019 Apr;41(4):2168-2180. doi: 10.3892/or.2019.7019. Epub 2019 Feb 18.
• [20] Striate palmoplantar keratoderma resulting from a frameshift mutation in the desmoglein 1 gene.J Dermatol Sci. 2007 Mar;45(3):161-6. doi: 10.1016/j.jdermsci.2006.11.013. Epub 2006 Dec 27.
• [21] 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.
• [22] Diffuse nonepidermolytic palmoplantar keratoderma caused by a recurrent nonsense mutation in DSG1. Arch Dermatol. 2005 May;141(5):625-8. doi: 10.1001/archderm.141.5.625.
• [23] Focal palmoplantar keratoderma caused by an autosomal dominant inherited mutation in the desmoglein 1 gene. Dermatology. 2006;212(2):117-22. doi: 10.1159/000090651.
• [24] N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma. Hum Mol Genet. 1999 Jun;8(6):971-6. doi: 10.1093/hmg/8.6.971.
• [25] The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAMSyndrome.J Invest Dermatol. 2020 Mar;140(3):556-567.e9. doi: 10.1016/j.jid.2019.08.433. Epub 2019 Aug 26.
• [26] Persistent kallikrein 5 activation induces atopic dermatitis-like skin architecture independent of PAR2 activity.J Allergy Clin Immunol. 2017 Nov;140(5):1310-1322.e5. doi: 10.1016/j.jaci.2017.01.025. Epub 2017 Feb 24.
• [27] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [28] 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.
• [29] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [30] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [31] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [32] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [33] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [34] 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.