Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT17HGXJ)

DOT Name	HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)
Synonyms	MHC class II antigen DMB; Really interesting new gene 7 protein
Gene Name	HLA-DMB
Related Disease	Becker muscular dystrophy ( ) Sarcoidosis ( ) Acute myelogenous leukaemia ( ) Acute myelomonocytic leukemia M4 ( ) Attention deficit hyperactivity disorder ( ) Bipolar disorder ( ) Coeliac disease ( ) Human T-lymphotropic virus 1 infectious disease ( ) Major depressive disorder ( ) Membranous glomerulonephritis ( ) Monocytic leukemia ( ) Multiple sclerosis ( ) Myocardial infarction ( ) Non-small-cell lung cancer ( ) Ovarian neoplasm ( ) Psoriasis ( ) Psoriatic arthritis ( ) Schizophrenia ( ) Systemic sclerosis ( ) Type-1 diabetes ( ) Hyperglycemia ( ) Lung squamous cell carcinoma ( ) Non-insulin dependent diabetes ( ) Type-1/2 diabetes ( )
UniProt ID	DMB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1HDM; 2BC4; 4FQX; 4GBX; 4I0P
Pfam ID	PF07654 ; PF00969
Sequence	MITFLPLLLGLSLGCTGAGGFVAHVESTCLLDDAGTPKDFTYCISFNKDLLTCWDPEENK MAPCEFGVLNSLANVLSQHLNQKDTLMQRLRNGLQNCATHTQPFWGSLTNRTRPPSVQVA KTTPFNTREPVMLACYVWGFYPAEVTITWRKNGKLVMPHSSAHKTAQPNGDWTYQTLSHL ALTPSYGDTYTCVVEHTGAPEPILRDWTPGLSPMQTLKVSVSAVTLGLGLIIFSLGVISW RRAGHSSYTPLPGSNYSEGWHIS
Function	Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.
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

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Becker muscular dystrophy	DIS5IYHL	Definitive	Biomarker	[1]
Sarcoidosis	DISE5B8Z	Definitive	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Biomarker	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[4]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[4]
Coeliac disease	DISIY60C	Strong	Biomarker	[5]
Human T-lymphotropic virus 1 infectious disease	DISN5C4M	Strong	Altered Expression	[6]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[7]
Monocytic leukemia	DIS8M755	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[8]
Myocardial infarction	DIS655KI	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[11]
Psoriasis	DIS59VMN	Strong	Biomarker	[12]
Psoriatic arthritis	DISLWTG2	Strong	Genetic Variation	[13]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[14]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[15]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[16]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[17]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[18]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[17]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[17]
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⏷ Show the Full List of 24 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

19 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 HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[23]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[24]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[25]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[26]
Piroxicam	DMTK234	Approved	Piroxicam affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Naproxen	DMZ5RGV	Approved	Naproxen affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Famotidine	DMRL3AB	Approved	Famotidine affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Topiramate	DM82Z30	Approved	Topiramate affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Albendazole	DMYZ57N	Approved	Albendazole affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Valdecoxib	DMAY7H4	Approved	Valdecoxib affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Vancomycin	DM3JFIH	Approved	Vancomycin affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
Ethosuximide	DMDZ9LT	Approved	Ethosuximide affects the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[28]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[29]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[32]
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⏷ Show the Full List of 19 Drug(s)

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 HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of HLA class II histocompatibility antigen, DM beta chain (HLA-DMB).	[31]
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References

1	Dystrophin immunofluorescence pattern in manifesting and asymptomatic carriers of Duchenne's and Becker muscular dystrophies of different ages.Neuromuscul Disord. 1991;1(3):177-83. doi: 10.1016/0960-8966(91)90022-k.
2	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.
3	Targeting cell-bound MUC1 on myelomonocytic, monocytic leukemias and phenotypically defined leukemic stem cells with anti-SEA module antibodies.Exp Hematol. 2019 Feb;70:97-108. doi: 10.1016/j.exphem.2018.12.002. Epub 2018 Dec 26.
4	Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.Lancet. 2013 Apr 20;381(9875):1371-1379. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28.
5	Celiac patients predominantly inherit HLA-DPB1*0101 positive haplotype from HLA-DQ2 homozygous parent.Hum Immunol. 1997 Apr 1;53(2):156-8. doi: 10.1016/S0198-8859(97)00027-X.
6	HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation.Sci Rep. 2017 Oct 31;7(1):14416. doi: 10.1038/s41598-017-14882-z.
7	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.
8	Risk alleles for multiple sclerosis identified by a genomewide study.N Engl J Med. 2007 Aug 30;357(9):851-62. doi: 10.1056/NEJMoa073493. Epub 2007 Jul 29.
9	Gut microbe-derived metabolite trimethylamine N-oxide accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis.J Mol Cell Cardiol. 2019 Sep;134:119-130. doi: 10.1016/j.yjmcc.2019.07.004. Epub 2019 Jul 9.
10	Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions.Hum Immunol. 2018 Jul;79(7):558-563. doi: 10.1016/j.humimm.2018.04.003. Epub 2018 Apr 12.
11	Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer.Clin Cancer Res. 2008 Dec 1;14(23):7667-73. doi: 10.1158/1078-0432.CCR-08-0479.
12	Association of TAP and HLA-DM genes with psoriasis in Koreans.J Invest Dermatol. 2003 Apr;120(4):616-22. doi: 10.1046/j.1523-1747.2003.12091.x.
13	HLA-DMA and HLA-DMB genotyping in patients with rheumatic diseases.Kaohsiung J Med Sci. 1999 May;15(5):263-7.
14	Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
15	Association of DM genes in systemic sclerosis is secondary to the association with HLA genes.Scand J Rheumatol. 1997;26(3):174-9. doi: 10.3109/03009749709065677.
16	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.
17	Impaired postprandial blood flow in adipose tissue may be an early marker of insulin resistance in type 2 diabetes.Diabetes Care. 2007 Dec;30(12):3128-30. doi: 10.2337/dc07-0699. Epub 2007 Sep 21.
18	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.
19	Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
20	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
21	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.
22	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
23	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
24	Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
25	Chromosomal radiosensitivity in two cell lineages derived from clinically radiosensitive cancer patients. Clin Cancer Res. 2005 Sep 1;11(17):6352-8. doi: 10.1158/1078-0432.CCR-04-1931.
26	The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
27	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.
28	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
29	Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
30	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
31	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.
32	Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.