Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD8HQT6)

DOT Name	C-type lectin domain family 10 member A (CLEC10A)
Synonyms	C-type lectin superfamily member 14; Macrophage lectin 2; CD antigen CD301
Gene Name	CLEC10A
Related Disease	Crohn disease ( ) Melanoma ( ) Tubular aggregate myopathy ( ) Ulcerative colitis ( ) Amyotrophic lateral sclerosis ( ) Atopic dermatitis ( ) B-cell neoplasm ( ) Bipolar disorder ( ) Cervical cancer ( ) Cervical carcinoma ( ) Coeliac disease ( ) Epithelial ovarian cancer ( ) Hepatocellular carcinoma ( ) HIV infectious disease ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Motor neurone disease ( ) Myocardial ischemia ( ) Neoplasm ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Primary cutaneous peripheral T-cell lymphoma not otherwise specified ( ) Prostate cancer ( ) Prostate carcinoma ( ) Squamous cell carcinoma ( ) Adult lymphoma ( ) Influenza ( ) Lymphoma ( ) Pediatric lymphoma ( ) Asthma ( ) Childhood acute megakaryoblastic leukemia ( ) Ebola virus infection ( ) Germ cell tumor ( ) Rheumatoid arthritis ( ) Schizophrenia ( )
UniProt ID	CLC10_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6PUV; 6PY1; 6W12; 6XIY
Pfam ID	PF00059 ; PF03954
Sequence	MTRTYENFQYLENKVKVQGFKNGPLPLQSLLQRLCSGPCHLLLSLGLGLLLLVIICVVGF QNSKFQRDLVTLRTDFSNFTSNTVAEIQALTSQGSSLEETIASLKAEVEGFKQERQAGVS ELQEHTTQKAHLGHCPHCPSVCVPVHSEMLLRVQQLVQDLKKLTCQVATLNNNASTEGTC CPVNWVEHQDSCYWFSHSGMSWAEAEKYCQLKNAHLVVINSREEQNFVQKYLGSAYTWMG LSDPEGAWKWVDGTDYATGFQNWKPGQPDDWQGHGLGGGEDCAHFHPDGRWNDDVCQRPY HWVCEAGLGQTSQESH
Function	Probable role in regulating adaptive and innate immune responses. Binds in a calcium-dependent manner to terminal galactose and N-acetylgalactosamine units, linked to serine or threonine. These sugar moieties are known as Tn-Ag and are expressed in a variety of carcinoma cells.
Reactome Pathway	Dectin-2 family (R-HSA-5621480 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[2]
Tubular aggregate myopathy	DISC11WH	Definitive	Biomarker	[3]
Ulcerative colitis	DIS8K27O	Definitive	Biomarker	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Altered Expression	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Biomarker	[6]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Coeliac disease	DISIY60C	Strong	Altered Expression	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
HIV infectious disease	DISO97HC	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Motor neurone disease	DISUHWUI	Strong	Altered Expression	[14]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[14]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[14]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[8]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[16]
Influenza	DIS3PNU3	moderate	Altered Expression	[17]
Lymphoma	DISN6V4S	moderate	Biomarker	[16]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[16]
Asthma	DISW9QNS	Limited	Biomarker	[18]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Limited	Biomarker	[19]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[20]
Germ cell tumor	DIS62070	Limited	Biomarker	[21]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[22]
Schizophrenia	DISSRV2N	Limited	Biomarker	[7]
------------------------------------------------------------------------------------


⏷ Show the Full List of 35 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of C-type lectin domain family 10 member A (CLEC10A).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C-type lectin domain family 10 member A (CLEC10A).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of C-type lectin domain family 10 member A (CLEC10A).	[25]
------------------------------------------------------------------------------------

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 C-type lectin domain family 10 member A (CLEC10A).	[26]
------------------------------------------------------------------------------------

References

1	Single nucleotide polymorphisms in C-type lectin genes, clustered in the IBD2 and IBD6 susceptibility loci, may play a role in the pathogenesis of inflammatory bowel diseases.Eur J Gastroenterol Hepatol. 2012 Aug;24(8):965-70. doi: 10.1097/MEG.0b013e328354f3d5.
2	The Concomitant Expression of Human Endogenous Retroviruses and Embryonic Genes in Cancer Cells under Microenvironmental Changes is a Potential Target for Antiretroviral Drugs.Cancer Microenviron. 2019 Dec;12(2-3):105-118. doi: 10.1007/s12307-019-00231-3. Epub 2019 Nov 5.
3	Immature O-glycans recognized by the macrophage glycoreceptor CLEC10A (MGL) are induced by 4-hydroxy-tamoxifen, oxidative stress and DNA-damage in breast cancer cells.Cell Commun Signal. 2019 Aug 27;17(1):107. doi: 10.1186/s12964-019-0420-9.
4	Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis.Acta Neuropathol Commun. 2019 Mar 18;7(1):45. doi: 10.1186/s40478-019-0698-2.
5	Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis.Allergol Int. 2018 Jan;67(1):103-108. doi: 10.1016/j.alit.2017.05.009. Epub 2017 Jun 24.
6	Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes.Am J Pathol. 1988 Jul;132(1):1-5.
7	Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.PLoS One. 2012;7(1):e30054. doi: 10.1371/journal.pone.0030054. Epub 2012 Jan 11.
8	MGL Ligand Expression Is Correlated to Lower Survival and Distant Metastasis in Cervical Squamous Cell and Adenosquamous Carcinoma.Front Oncol. 2019 Jan 29;9:29. doi: 10.3389/fonc.2019.00029. eCollection 2019.
9	Low-grade intestinal lymphoma of intraepithelial T lymphocytes with concomitant enteropathy-associated T cell lymphoma: case report suggesting a possible histogenetic relationship.Hum Pathol. 1989 Sep;20(9):909-13. doi: 10.1016/0046-8177(89)90105-6.
10	An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides.J Immunother Cancer. 2018 Apr 17;6(1):28. doi: 10.1186/s40425-018-0339-5.
11	The cyanobacterial oligopeptides microginins induce DNA damage in the human hepatocellular carcinoma (HepG2) cell line.Chemosphere. 2020 Feb;240:124880. doi: 10.1016/j.chemosphere.2019.124880. Epub 2019 Sep 16.
12	Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers.Retrovirology. 2017 Aug 22;14(1):41. doi: 10.1186/s12977-017-0365-2.
13	Identification and association study with lung cancer for novel insertion polymorphisms of human endogenous retrovirus.Carcinogenesis. 2013 Nov;34(11):2531-8. doi: 10.1093/carcin/bgt253. Epub 2013 Jul 19.
14	Disruption by SaCas9 Endonuclease of HERV-Kenv, a Retroviral Gene with Oncogenic and Neuropathogenic Potential, Inhibits Molecules Involved in Cancer and Amyotrophic Lateral Sclerosis.Viruses. 2018 Aug 7;10(8):412. doi: 10.3390/v10080412.
15	Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
16	Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer.J Virol. 2008 Oct;82(19):9329-36. doi: 10.1128/JVI.00646-08. Epub 2008 Jul 16.
17	Pregnancy Induces a Steady-State Shift in Alveolar Macrophage M1/M2 Phenotype That Is Associated With a Heightened Severity of Influenza Virus Infection: Mechanistic Insight Using Mouse Models.J Infect Dis. 2019 May 5;219(11):1823-1831. doi: 10.1093/infdis/jiy732.
18	Impact of endobronchial allergen provocation on macrophage phenotype in asthmatics.BMC Immunol. 2014 Mar 10;15:12. doi: 10.1186/1471-2172-15-12.
19	Induction of the erythropoietin receptor gene and acquisition of responsiveness to erythropoietin by stem cell factor in HML/SE, a human leukemic cell line.J Biol Chem. 1998 Jul 3;273(27):16921-6. doi: 10.1074/jbc.273.27.16921.
20	Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin.Biochem Biophys Res Commun. 2011 Apr 1;407(1):74-8. doi: 10.1016/j.bbrc.2011.02.110. Epub 2011 Mar 6.
21	Expression patterns of transcribed human endogenous retrovirus HERV-K(HML-2) loci in human tissues and the need for a HERV Transcriptome Project.BMC Genomics. 2008 Jul 29;9:354. doi: 10.1186/1471-2164-9-354.
22	Human endogenous retrovirus HERV-K(HML-2) Rec expression and transcriptional activities in normal and rheumatoid arthritis synovia.J Rheumatol. 2006 Jan;33(1):16-23.
23	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
24	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.
25	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
26	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.