Details of Drug Off-Target (DOT)

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

DOT Name Butyrophilin-like protein 2 (BTNL2)
Synonyms BTL-II
Gene Name BTNL2
Related Disease
Leprosy ( )
Lung adenocarcinoma ( )
Malaria ( )
Marginal zone lymphoma ( )
Narcolepsy ( )
Prostate cancer ( )
Prostate carcinoma ( )
Alzheimer disease ( )
Autoimmune disease ( )
Autoimmune thyroid disease ( )
Cardiomyopathy ( )
Colitis ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Dilated cardiomyopathy ( )
Dilated cardiomyopathy 1A ( )
Epstein barr virus infection ( )
Frontotemporal dementia ( )
Graves disease ( )
Hepatitis A virus infection ( )
Hepatitis B virus infection ( )
High blood pressure ( )
Inflammation ( )
Inflammatory bowel disease ( )
Membranous glomerulonephritis ( )
Multiple sclerosis ( )
Myasthenia gravis ( )
Myocardial infarction ( )
Neoplasm ( )
Osteoarthritis ( )
Psoriasis ( )
Pulmonary sarcoidosis ( )
Pulmonary tuberculosis ( )
Rosacea ( )
Schizophrenia ( )
Systemic lupus erythematosus ( )
Tuberculosis ( )
Type-1 diabetes ( )
Ulcerative colitis ( )
Uveal Melanoma ( )
Advanced cancer ( )
Sarcoidosis ( )
Asthma ( )
Graft-versus-host disease ( )
Knee osteoarthritis ( )
Rheumatoid arthritis ( )
Vitiligo ( )
UniProt ID
BTNL2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF07686
Sequence
MVDFPGYNLSGAVASFLFILLTMKQSEDFRVIGPAHPILAGVGEDALLTCQLLPKRTTMH
VEVRWYRSEPSTPVFVHRDGVEVTEMQMEEYRGWVEWIENGIAKGNVALKIHNIQPSDNG
QYWCHFQDGNYCGETSLLLKVAGLGSAPSIHMEGPGESGVQLVCTARGWFPEPQVYWEDI
RGEKLLAVSEHRIQDKDGLFYAEATLVVRNASAESVSCLVHNPVLTEEKGSVISLPEKLQ
TELASLKVNGPSQPILVRVGEDIQLTCYLSPKANAQSMEVRWDRSHRYPAVHVYMDGDHV
AGEQMAEYRGRTVLVSDAIDEGRLTLQILSARPSDDGQYRCLFEKDDVYQEASLDLKVVS
LGSSPLITVEGQEDGEMQPMCSSDGWFPQPHVPWRDMEGKTIPSSSQALTQGSHGLFHVQ
TLLRVTNISAVDVTCSISIPFLGEEKIATFSLSESRMTFLWKTLLVWGLLLAVAVGLPRK
RS
Function Negative regulator of T-cell proliferation.
Tissue Specificity Expressed in brain, heart, kidney, liver, pancreas, ovary, leukocyte, small intestine, testis and thymus.
Reactome Pathway
Butyrophilin (BTN) family interactions (R-HSA-8851680 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Leprosy DISAA4UI Definitive Genetic Variation [1]
Lung adenocarcinoma DISD51WR Definitive Genetic Variation [2]
Malaria DISQ9Y50 Definitive Biomarker [3]
Marginal zone lymphoma DISLZ4AO Definitive Genetic Variation [4]
Narcolepsy DISLCNLI Definitive Genetic Variation [5]
Prostate cancer DISF190Y Definitive Genetic Variation [6]
Prostate carcinoma DISMJPLE Definitive Genetic Variation [6]
Alzheimer disease DISF8S70 Strong Genetic Variation [7]
Autoimmune disease DISORMTM Strong Genetic Variation [6]
Autoimmune thyroid disease DISIHC6A Strong Genetic Variation [8]
Cardiomyopathy DISUPZRG Strong Genetic Variation [9]
Colitis DISAF7DD Strong Altered Expression [10]
Coronary atherosclerosis DISKNDYU Strong Biomarker [11]
Coronary heart disease DIS5OIP1 Strong Biomarker [12]
Dilated cardiomyopathy DISX608J Strong Genetic Variation [9]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Genetic Variation [9]
Epstein barr virus infection DISOO0WT Strong Genetic Variation [13]
Frontotemporal dementia DISKYHXL Strong Biomarker [7]
Graves disease DISU4KOQ Strong Genetic Variation [14]
Hepatitis A virus infection DISUMFQV Strong Genetic Variation [15]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [15]
High blood pressure DISY2OHH Strong Altered Expression [12]
Inflammation DISJUQ5T Strong Biomarker [10]
Inflammatory bowel disease DISGN23E Strong Genetic Variation [16]
Membranous glomerulonephritis DISFSUKQ Strong Genetic Variation [17]
Multiple sclerosis DISB2WZI Strong Genetic Variation [18]
Myasthenia gravis DISELRCI Strong Genetic Variation [19]
Myocardial infarction DIS655KI Strong Biomarker [20]
Neoplasm DISZKGEW Strong Altered Expression [6]
Osteoarthritis DIS05URM Strong Biomarker [21]
Psoriasis DIS59VMN Strong Genetic Variation [22]
Pulmonary sarcoidosis DIS1XQCN Strong Biomarker [23]
Pulmonary tuberculosis DIS6FLUM Strong Genetic Variation [24]
Rosacea DIS02PWG Strong Genetic Variation [25]
Schizophrenia DISSRV2N Strong Genetic Variation [26]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [27]
Tuberculosis DIS2YIMD Strong Biomarker [28]
Type-1 diabetes DIS7HLUB Strong Biomarker [29]
Ulcerative colitis DIS8K27O Strong Genetic Variation [30]
Uveal Melanoma DISA7ZGL Strong Genetic Variation [6]
Advanced cancer DISAT1Z9 moderate Genetic Variation [31]
Sarcoidosis DISE5B8Z moderate Genetic Variation [32]
Asthma DISW9QNS Limited Genetic Variation [33]
Graft-versus-host disease DIS0QADF Limited Biomarker [34]
Knee osteoarthritis DISLSNBJ Limited Genetic Variation [35]
Rheumatoid arthritis DISTSB4J Limited Genetic Variation [36]
Vitiligo DISR05SL Limited Genetic Variation [37]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Butyrophilin-like protein 2 (BTNL2). [38]
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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 Butyrophilin-like protein 2 (BTNL2). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Butyrophilin-like protein 2 (BTNL2). [40]
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References

1 PARK2 and proinflammatory/anti-inflammatory cytokine gene interactions contribute to the susceptibility to leprosy: a case-control study of North Indian population.BMJ Open. 2014 Feb 27;4(2):e004239. doi: 10.1136/bmjopen-2013-004239.
2 Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.Hum Mol Genet. 2017 Jan 15;26(2):454-465. doi: 10.1093/hmg/ddw414.
3 The T-Cell Inhibitory Molecule Butyrophilin-Like 2 Is Up-regulated in Mild Plasmodium falciparum Infection and Is Protective During Experimental Cerebral Malaria.J Infect Dis. 2015 Oct 15;212(8):1322-31. doi: 10.1093/infdis/jiv217. Epub 2015 Apr 15.
4 A genome-wide association study of marginal zone lymphoma shows association to the HLA region.Nat Commun. 2015 Jan 8;6:5751. doi: 10.1038/ncomms6751.
5 Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
6 Analysis of the Expression and Single-Nucleotide Variant Frequencies of the Butyrophilin-like 2 Gene in Patients With Uveal Melanoma.JAMA Ophthalmol. 2016 Oct 1;134(10):1125-1133. doi: 10.1001/jamaophthalmol.2016.2691.
7 Association of Frontotemporal Dementia GWAS Loci with Late-Onset Alzheimer's Disease in a Northern Han Chinese Population.J Alzheimers Dis. 2016 Feb 26;52(1):43-50. doi: 10.3233/JAD-151073.
8 Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes.J Autoimmun. 2015 Jun;60:32-9. doi: 10.1016/j.jaut.2015.03.006. Epub 2015 Apr 27.
9 Association of genetic polymorphisms on BTNL2 with susceptibility to and prognosis of dilated cardiomyopathy in a Chinese population.Int J Clin Exp Pathol. 2015 Sep 1;8(9):10488-99. eCollection 2015.
10 BTNL2, a butyrophilin/B7-like molecule, is a negative costimulatory molecule modulated in intestinal inflammation.J Immunol. 2007 Feb 1;178(3):1523-33. doi: 10.4049/jimmunol.178.3.1523.
11 The Value of the SYNTAX Score II in Predicting Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.Rev Esp Cardiol (Engl Ed). 2018 Aug;71(8):628-637. doi: 10.1016/j.rec.2017.10.014. Epub 2017 Nov 28.
12 Assessment of Relationship Between C-Reactive Protein to Albumin Ratio and Coronary Artery Disease Severity in Patients With Acute Coronary Syndrome.Angiology. 2019 Apr;70(4):361-368. doi: 10.1177/0003319717743325. Epub 2017 Nov 26.
13 A genome-wide integrative genomic study localizes genetic factors influencing antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1).PLoS Genet. 2013;9(1):e1003147. doi: 10.1371/journal.pgen.1003147. Epub 2013 Jan 10.
14 Association of the BTNL2 rs2076530 single nucleotide polymorphism with Graves' disease appears to be secondary to DRB1 exon 2 position beta74.Clin Endocrinol (Oxf). 2006 Oct;65(4):429-32. doi: 10.1111/j.1365-2265.2006.02586.x.
15 Key HLA-DRB1-DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine.Hepatology. 2018 Sep;68(3):848-858. doi: 10.1002/hep.29876. Epub 2018 Apr 27.
16 Pooled sequencing of 531 genes in inflammatory bowel disease identifies an associated rare variant in BTNL2 and implicates other immune related genes.PLoS Genet. 2015 Feb 11;11(2):e1004955. doi: 10.1371/journal.pgen.1004955. eCollection 2015 Feb.
17 Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
18 Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.PLoS One. 2013;8(3):e58352. doi: 10.1371/journal.pone.0058352. Epub 2013 Mar 5.
19 Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
20 Comparison of the Predictive Roles of Risk Scores of In-Hospital Major Adverse Cardiovascular Events in Patients with Non-ST Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.Med Princ Pract. 2018;27(5):459-465. doi: 10.1159/000489399. Epub 2018 Apr 19.
21 Genetic epidemiology of hip and knee osteoarthritis.Nat Rev Rheumatol. 2011 Jan;7(1):23-32. doi: 10.1038/nrrheum.2010.191. Epub 2010 Nov 16.
22 Correlation analysis of the HLA-DPB1*05:01 and BTNL2 genes within the histocompatibility complex region with a clinical phenotype of psoriasis vulgaris in the Chinese Han population.J Gene Med. 2017 Sep;19(9-10). doi: 10.1002/jgm.2961. Epub 2017 Sep 19.
23 Butyrophilin-like 2 in pulmonary sarcoidosis: a factor for susceptibility and progression?.Hum Immunol. 2011 Apr;72(4):342-7. doi: 10.1016/j.humimm.2011.01.011. Epub 2011 Jan 20.
24 Allelic variation in BTNL2 and susceptibility to tuberculosis in a South African population.Microbes Infect. 2007 Apr;9(4):522-8. doi: 10.1016/j.micinf.2007.01.011. Epub 2007 Jan 27.
25 Genetic Predisposition to Rosacea.Dermatol Clin. 2018 Apr;36(2):87-92. doi: 10.1016/j.det.2017.11.002. Epub 2017 Dec 16.
26 Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia.Transl Psychiatry. 2019 Oct 17;9(1):256. doi: 10.1038/s41398-019-0596-1.
27 GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
28 Analysis of the association between BTNL2 polymorphism and tuberculosis in Chinese Han population.Infect Genet Evol. 2010 May;10(4):517-21. doi: 10.1016/j.meegid.2010.02.006. Epub 2010 Feb 20.
29 BTNL2-Ig Protein Attenuates Type 1 Diabetes in Non-Obese Diabetic (NOD) Mice.Adv Healthc Mater. 2019 May;8(9):e1800987. doi: 10.1002/adhm.201800987. Epub 2019 Mar 18.
30 Deep Resequencing of Ulcerative Colitis-Associated Genes Identifies Novel Variants in Candidate Genes in the Korean Population.Inflamm Bowel Dis. 2018 Jul 12;24(8):1706-1717. doi: 10.1093/ibd/izy122.
31 Lack of correlation of BTNL2 polymorphism and cancer risk in sarcoidosis. BTNL2 and cancer risk in sarcoidosis.Sarcoidosis Vasc Diffuse Lung Dis. 2014 Jul 8;31(2):136-41.
32 BTNL2 gene polymorphism and sarcoid uveitis.Br J Ophthalmol. 2019 Dec;103(12):1690-1694. doi: 10.1136/bjophthalmol-2018-312949. Epub 2019 Mar 14.
33 Identification of Four Novel Loci in Asthma in European American and African American Populations.Am J Respir Crit Care Med. 2017 Feb 15;195(4):456-463. doi: 10.1164/rccm.201604-0861OC.
34 In vivo administration of recombinant BTNL2-Fc fusion protein ameliorates graft-versus-host disease in mice.Cell Immunol. 2019 Jan;335:22-29. doi: 10.1016/j.cellimm.2018.10.008. Epub 2018 Oct 26.
35 New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study.PLoS One. 2010 Mar 18;5(3):e9723. doi: 10.1371/journal.pone.0009723.
36 Exome sequencing identifies novel rheumatoid arthritis-susceptible variants in the BTNL2.J Hum Genet. 2013 Apr;58(4):210-5. doi: 10.1038/jhg.2013.2. Epub 2013 Jan 31.
37 Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.Nat Genet. 2012 May 6;44(6):676-80. doi: 10.1038/ng.2272.
38 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
39 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.
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.