Details of Drug Off-Target (DOT)

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

• DOT Name: HLA class II histocompatibility antigen, DO beta chain (HLA-DOB)
• Synonyms: MHC class II antigen DOB
• Gene Name: HLA-DOB
• Related Disease:
  Hepatitis B virus infection
  Acute myelogenous leukaemia
  Advanced cancer
  Autoimmune disease
  Narcolepsy
  Non-insulin dependent diabetes
  Plasma cell myeloma
  Rheumatoid arthritis
  Sarcoidosis
  Type-1 diabetes
  Ankylosing spondylitis
  Breast cancer
  Breast carcinoma
  Hepatitis C virus infection
  Lung carcinoma
  Schizophrenia
• UniProt ID: DOB_HUMAN
• PDB ID: 4I0P
• Pfam ID: PF07654 ; PF00969
• Sequence:
  MGSGWVPWVVALLVNLTRLDSSMTQGTDSPEDFVIQAKADCYFTNGTEKVQFVVRFIFNL
  EEYVRFDSDVGMFVALTKLGQPDAEQWNSRLDLLERSRQAVDGVCRHNYRLGAPFTVGRK
  VQPEVTVYPERTPLLHQHNLLHCSVTGFYPGDIKIKWFLNGQEERAGVMSTGPIRNGDWT
  FQTVVMLEMTPELGHVYTCLVDHSSLLSPVSVEWRAQSEYSWRKMLSGIAAFLLGLIFLL
  VGIVIQLRAQKGYVRTQMSGNEVSRAVLLPQSC
• Function: Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells. Modifies peptide exchange activity of HLA-DM.
• KEGG Pathway:
  Phagosome (hsa04145)
  Cell adhesion molecules (hsa04514)
  Antigen processing and presentation (hsa04612)
  Hematopoietic cell lineage (hsa04640)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Intesti.l immune network for IgA production (hsa04672)
  Type I diabetes mellitus (hsa04940)
  Leishmaniasis (hsa05140)
  Toxoplasmosis (hsa05145)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Influenza A (hsa05164)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Asthma (hsa05310)
  Autoimmune thyroid disease (hsa05320)
  Inflammatory bowel disease (hsa05321)
  Systemic lupus erythematosus (hsa05322)
  Rheumatoid arthritis (hsa05323)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Viral myocarditis (hsa05416)
• Reactome Pathway: MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[3]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[7]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[8]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[9]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[10]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[11]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[11]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[12]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[13]
Schizophrenia	DISSRV2N	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of HLA class II histocompatibility antigen, DO beta chain (HLA-DOB).	[15]
Trimethoprim	DMM7CHK	Approved	Trimethoprim affects the expression of HLA class II histocompatibility antigen, DO beta chain (HLA-DOB).	[16]
Meropenem	DM62UHC	Approved	Meropenem affects the expression of HLA class II histocompatibility antigen, DO beta chain (HLA-DOB).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of HLA class II histocompatibility antigen, DO beta chain (HLA-DOB).	[18]

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 decreases the methylation of HLA class II histocompatibility antigen, DO beta chain (HLA-DOB).	[17]

References

• [1] Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob.Immunity. 2017 Aug 15;47(2):310-322.e7. doi: 10.1016/j.immuni.2017.07.013.
• [2] Association between single nucleotide polymorphisms within HLA region and disease relapse for patients with hematopoietic stem cell transplantation.Sci Rep. 2019 Sep 24;9(1):13731. doi: 10.1038/s41598-019-50111-5.
• [3] Novel polymorphisms in HLA-DOA and HLA-DOB in B-cell malignancies.Immunogenetics. 2002 Nov;54(8):591-5. doi: 10.1007/s00251-002-0500-6. Epub 2002 Oct 9.
• [4] 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.
• [5] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [6] Identification of human leucocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocyte epitopes derived from HLA-DO as a novel target for multiple myeloma.Br J Haematol. 2013 Nov;163(3):343-51. doi: 10.1111/bjh.12544. Epub 2013 Aug 30.
• [7] An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis.Rheumatology (Oxford). 2016 Jan;55(1):149-55. doi: 10.1093/rheumatology/kev285. Epub 2015 Aug 13.
• [8] High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.Am J Respir Crit Care Med. 2016 May 1;193(9):1008-22. doi: 10.1164/rccm.201507-1372OC.
• [9] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [10] Clinical and genetic characteristics of ankylosing spondylitis patients with peripheral arthritis at disease onset.Clin Exp Rheumatol. 2019 Mar-Apr;37(2):215-221. Epub 2018 Sep 17.
• [11] The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels.Cancer Chemother Pharmacol. 2013 Mar;71(3):593-601. doi: 10.1007/s00280-012-2034-4. Epub 2012 Dec 11.
• [12] Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection.PLoS One. 2015 Apr 13;10(4):e0123513. doi: 10.1371/journal.pone.0123513. eCollection 2015.
• [13] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [14] Evidence for Association of Cell Adhesion Molecules Pathway and NLGN1 Polymorphisms with Schizophrenia in Chinese Han Population.PLoS One. 2015 Dec 16;10(12):e0144719. doi: 10.1371/journal.pone.0144719. eCollection 2015.
• [15] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [16] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [17] 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.
• [18] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.