HLA-DRB1

Summary

HLA-DRB1 (major histocompatibility complex, class II, DR beta 1, HGNC:4948) is a protein-coding gene on chromosome 6p21.32, encoding HLA class II histocompatibility antigen, DRB1 beta chain (P01911). A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.

HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and some alleles have increased frequencies associated with certain diseases or conditions. For example, DRB1*1302 has been related to acute and chronic hepatitis B virus persistence. There are multiple pseudogenes of this gene.

Source: NCBI Gene 3123 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 303
• Clinical variants (ClinVar): 132 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 306
• Druggable target: yes
• MANE Select transcript: NM_002124

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4948
Approved symbol	HLA-DRB1
Name	major histocompatibility complex, class II, DR beta 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196126
Ensembl biotype	protein_coding
OMIM	142857
Entrez	3123

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000360004, ENST00000696610, ENST00000696611, ENST00000696612, ENST00000696613, ENST00000696614, ENST00000859897, ENST00000859898, ENST00000859899, ENST00000859900, ENST00000859901, ENST00000963203

RefSeq mRNA: 1 — MANE Select: NM_002124 NM_002124

CCDS: CCDS47409

Canonical transcript exons

ENST00000360004 — 6 exons

Exon	Start	End
ENSE00003967851	32581557	32581838
ENSE00003967852	32589643	32589848
ENSE00003967854	32580746	32580856
ENSE00003967857	32584109	32584378
ENSE00003967859	32580247	32580270
ENSE00003978165	32578775	32579104

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 99.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2366 / max 37.9577, expressed in 114 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72978	6.8048	524
72979	2.9042	547
72976	0.2769	120
72977	0.2366	114

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	99.55	gold quality
granulocyte	CL:0000094	99.53	gold quality
right lung	UBERON:0002167	99.48	gold quality
leukocyte	CL:0000738	99.46	gold quality
lymph node	UBERON:0000029	99.46	gold quality
monocyte	CL:0000576	99.45	gold quality
spleen	UBERON:0002106	99.45	gold quality
upper lobe of left lung	UBERON:0008952	99.45	gold quality
gall bladder	UBERON:0002110	99.26	gold quality
duodenum	UBERON:0002114	99.26	gold quality
right coronary artery	UBERON:0001625	99.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.95	gold quality
rectum	UBERON:0001052	98.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.81	gold quality
smooth muscle tissue	UBERON:0001135	98.79	gold quality
adipose tissue	UBERON:0001013	98.71	gold quality
tibial nerve	UBERON:0001323	98.61	gold quality
fallopian tube	UBERON:0003889	98.45	gold quality
omental fat pad	UBERON:0010414	98.43	gold quality
small intestine	UBERON:0002108	98.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.35	gold quality
apex of heart	UBERON:0002098	98.30	gold quality
metanephros cortex	UBERON:0010533	98.30	gold quality
adult mammalian kidney	UBERON:0000082	98.25	gold quality
descending thoracic aorta	UBERON:0002345	98.13	gold quality
left coronary artery	UBERON:0001626	98.08	gold quality
thoracic mammary gland	UBERON:0005200	98.07	gold quality
left uterine tube	UBERON:0001303	98.01	gold quality
blood	UBERON:0000178	97.84	gold quality
endocervix	UBERON:0000458	97.66	gold quality

Single-cell (SCXA)

Detected in 52 experiment(s), a significant marker in 46.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	14842.99
E-GEOD-135922	yes	9340.32
E-HCAD-36	yes	8926.77
E-CURD-120	yes	8537.33
E-CURD-126	yes	8502.74
E-MTAB-8322	yes	8305.37
E-HCAD-15	yes	8183.42
E-MTAB-9906	yes	7518.17
E-HCAD-24	yes	6590.85
E-CURD-79	yes	6442.94
E-GEOD-84465	yes	5756.27
E-GEOD-134144	yes	5300.28
E-MTAB-6308	yes	4302.38
E-MTAB-8410	yes	3937.56
E-GEOD-130148	yes	3812.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF3, ATF4, CIITA, DDIT3, DNMT3A, EHF, EPAS1, FOXC1, GLI3, ILF3, JUN, MYC, MYCN, NFKB, NR1H3, NR1H4, NR1I2, NR1I3, NR2C1, NR2C2, RARA, REL, RELA, RFX5, RFXANK, RFXAP, SP1, STAT1, THRA, TP53, VDR, VSX2, ZHX2

miRNA regulators (miRDB)

13 targeting HLA-DRB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-1343-5P	96.48	66.06	1506

Literature-anchored findings (GeneRIF, showing 19)

• alleles associated with multiple sclerosis (PMID:11519010)
• structural analysis of haplotypes binding an immunodominant peptide derived from type II collagen (PMID:11751969)
• Prevalence of human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti children with juvenile rheumatoid arthritis (PMID:11841481)
• association of TNF alleles with HLA-DR, -DQ and -B alleles in 216 healthy individuals from the north of England (PMID:11841486)
• support is provided for roles of the DQ genes and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining susceptibility to type 1 diabetes (PMID:11841488)
• A study was made on any association between these alleles and rheumatoid arthritis in a population of Colombian women. (PMID:11857065)
• Genotyping of HLA-DRB1 alleles in endometriosis. (PMID:11870103)
• Heterogeneity of HLA-DRB1*04 and its associated haplotypes in the North Indian population. (PMID:11916167)
• Genetic dissection of the human leukocyte antigen region by use of haplotypes of Tasmanians with multiple sclerosis. (PMID:11923913)
• Identification of sequence errors in HLA-DRB1*0801 and HLA-DRB1*12011 (PMID:11972881)
• Complete cDNA sequences of the HLA-DRB1*14011, *1402, *1403 and *1404 alleles. (PMID:11972886)
• HLA-DRB1, DQB1, and DQA1 allele profile in Brazilian patients with type 1 diabetes mellitus. (PMID:12021129)
• Henoch-Schonlein purpura and cutaneous leukocytoclastic angiitis exhibit different HLA-DRB1 genotype associations. (PMID:12022354)
• Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus (PMID:12028537)
• Novel HLA-DRB1 alleles discovered during routine sequencing based typing, DRB1*03052, DRB1*04032, DRB1*1139 and DRB1*1346. (PMID:12028548)
• Two new HLA-DRB1 alleles have been identified by sequencing based typing (SBT). (PMID:12028549)
• The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder. (PMID:12039413)
• high frequency of HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype in paroxysmal nocturnal hemoglobinuria(PNH), including AA-PNH syndrome, and aplastic anemia (AA) patients. (PMID:12070003)
• HLA-DRB1*0701 restricted crosspriming against HLA-DRB1*1301; HLA-DRB1*1101 restricted crosspriming against HLA-DRB1*0101 (PMID:12072187)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2-Eb2	ENSMUSG00000067341

Paralogs (13): B2M (ENSG00000166710), HLA-DQB1 (ENSG00000179344), HLA-DQA1 (ENSG00000196735), HLA-DRB5 (ENSG00000198502), HLA-DOA (ENSG00000204252), HLA-DMA (ENSG00000204257), HLA-DRA (ENSG00000204287), HLA-DPB1 (ENSG00000223865), HLA-DPA1 (ENSG00000231389), HLA-DQB2 (ENSG00000232629), HLA-DQA2 (ENSG00000237541), HLA-DOB (ENSG00000241106), HLA-DMB (ENSG00000242574)

Protein

Protein identifiers

HLA class II histocompatibility antigen, DRB1 beta chain — P01911 (reviewed: P01911)

Alternative names: Human leukocyte antigen DRB1

All UniProt accessions (4): A0A8Q3WLF4, D7RIH8, P01911, X5DNQ0

UniProt curated annotations — full annotation on UniProt →

Function. A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB1-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes. In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins. Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance. The selection of the immunodominant epitopes follows two processing modes: ‘bind first, cut/trim later’ for pathogen-derived antigenic peptides and ‘cut first, bind later’ for autoantigens/self-peptides. The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules. Allele DRB101:01: Displays an immunodominant epitope derived from Bacillus anthracis pagA/protective antigen, PA (KLPLYISNPNYKVNVYAVT), to both naive and PA-specific memory CD4-positive T cells. Presents immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (PHQFINLRSNNSATLIVPYV), contributing to viral clearance. Displays commonly recognized peptides derived from IAV external protein HA (PKYVKQNTLKLAT and SNGNFIAPEYAYKIVK) and from internal proteins M, NP and PB1, with M-derived epitope (GLIYNRMGAVTTEV) being the most immunogenic. Presents a self-peptide derived from COL4A3 (GWISLWKGFSF) to TCR (TRAV14 biased) on CD4-positive, FOXP3-positive regulatory T cells and mediates immune tolerance to self. May present peptides derived from oncofetal trophoblast glycoprotein TPBG 5T4, known to be recognized by both T-helper 1 and regulatory T cells. Displays with low affinity a self-peptide derived from MBP (VHFFKNIVTPRTP). Allele DRB103:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance. Displays self-peptides derived from retinal SAG (NRERRGIALDGKIKHE) and thyroid TG (LSSVVVDPSIRHFDV). Presents viral epitopes derived from HHV-6B gH/U48 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection. Presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and long-term protection. Allele DRB104:01: Presents an immunodominant bacterial epitope derived from M.tuberculosis esxB/culture filtrate antigen CFP-10 (EISTNIRQAGVQYSR), eliciting CD4-positive T cell effector functions such as IFNG production and cytotoxic activity. May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance. Presents tumor epitopes derived from melanoma-associated TYR antigen (QNILLSNAPLGPQFP and DYSYLQDSDPDSFQD), triggering CD4-positive T cell effector functions such as GMCSF production. Displays preferentially citrullinated self-peptides derived from VIM (GVYATR/citSSAVR and SAVRAR/citSSVPGVR) and ACAN (VVLLVATEGR/ CitVRVNSAYQDK). Displays self-peptides derived from COL2A1. Allele DRB104:02: Displays native or citrullinated self-peptides derived from VIM. Allele DRB104:04: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (HIVMQYMYVPPGAPIPTTRN) and VP2 (RGDSTITSQDVANAVVGYGV), contributing to viral clearance. Displays preferentially citrullinated self-peptides derived from VIM (SAVRAR/citSSVPGVR). Allele DRB104:05: May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies. Allele DRB105:01: Presents an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. Allele DRB107:01: Upon EBV infection, presents latent antigen EBNA2 peptide (PRSPTVFYNIPPMPLPPSQL) to CD4-positive T cells, driving oligoclonal expansion and selection of a dominant virus-specific memory T cell subset with cytotoxic potential to directly eliminate virus-infected B cells. May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (VPYVNAVPMDSMVRHNNWSL), contributing to viral clearance. In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (MTEYKLVVVGAVGVGKSALTIQLI), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies. In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a KRAS neoantigen (MTEYKLVVVGAVGVGKSALTIQLI) carrying G12V hotspot driver mutation and may mediate tumor regression. Allele DRB111:01: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SDRIIQITRGDSTITSQDVA), contributing to viral clearance. Presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and longterm protection. In the context of tumor immunesurveillance, may present tumor-derived neoantigens to CD4-positive T cells and trigger anti-tumor helper functions. Allele DRB113:01: Presents viral epitopes derived from HHV-6B antigens to polyfunctional CD4-positive T cells implicated in control of HHV-6B infection. Allele DRB115:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SNNSATLIVPYVNAVPMDSM), contributing to viral clearance. Displays a self-peptide derived from MBP (ENPVVHFFKNIVTPR). May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies. Allele DRB115:02: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies. (Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.

Subunit / interactions. Heterotrimer that consists of an alpha chain HLA-DRA, a beta chain HLA-DRB1 and a peptide (peptide-MHCII). Newly synthesized alpha and beta chains forms a heterodimer (MHCII) that associates with the CD74/invariant chain (Ii) in the endoplasmic reticulum (ER). Ii is a trimer composed of three subunits and each subunit interacts with one MHCII dimer, blocking the peptide-binding cleft. As a result, MHCII molecules cannot bind peptides present in the ER. The complex of MHCII and CD74/Ii is transported in vesicles from ER to Golgi to lysosomes, where it encounters antigenic peptides generated via proteolysis of endocytosed antigens. MHCII dimers are dissociated from CD74/Ii by the combined action of proteolysis and HLA-DM. Lysosomal enzymes such as cathepsin, degrade CD74/Ii leaving a 24 amino acid remnant called class II-associated Ii or CLIP. Interacts (via the peptide binding cleft) with CLIP; this interaction inhibits antigen peptide binding before entry in the endosomal compartment. The displacement of CLIP and replacement by a high affinity peptide in lysosomes is performed by HLA-DM heterodimer. HLA-DM catalyzes CLIP dissociation from MHCII, stabilizes empty MHCII and mediates the selection of high affinity peptides. Interacts with HLA-DM heterodimer; this interaction is direct. Interacts with TCR (via CDR3). Interacts (via beta-2 domain) with CD4 coreceptor (via Ig-like V-type domain); this interaction is of exceptionally low affinity yet necessary for optimal recognition of antigenic peptides. (Microbial infection) Interacts with Staphylococcus aureus enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1, enterotoxin D/entD and enterotoxin H/entH. Enterotoxins bind outside the peptide-binding cleft of MHCII: enterotoxin H/entH interacts via the beta-1 domain of MHCII and in a zinc-dependent way, whereas enterotoxin B/entB interacts primarily via the alpha-1 domain. (Microbial infection) Interacts with Epstein-Barr virus gp42 protein.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Lysosome membrane. Late endosome membrane. Autolysosome membrane.

Tissue specificity. Expressed in professional APCs: monocyte/macrophages, dendritic cells and B cells (at protein level). Expressed in thymic epithelial cells (at protein level).

Post-translational modifications. Ubiquitinated by MARCHF1 and MARCHF8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHCII.

Disease relevance. In populations of European descent, allele DRB101:03 is associated with increased susceptibility to Crohn disease and colonic ulcerative colitis. Decreased heterozygosity in individuals with colonic ulcerative colitis suggests that it acts as a recessive risk allele. Sarcoidosis 1 (SS1) [MIM:181000] An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB104:02, DRB111:01 and DRB112:01 are associated with sarcoidosis. Allele DRB104:02 is significantly associated with specific sarcodosis phenotypes such as eye, parotid and salivary gland involvement. Multiple sclerosis (MS) [MIM:126200] A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. In populations of European descent, allele DRB115:01 has the strongest association with multiple sclerosis among all HLA class II alleles. Additional risk is associated with the strongly linked alleles DRB103:01 and DQB102:01 as well as with allele DRB113:03. It is postulated that bacterial or viral infection triggers the autoimmune MS. Microbial peptides having low affinity crossreactivity to MBP autoantigen, may stimulate autoreactive T cells via molecular mimicry and initiate the autoimmune inflammation. Allele DRB115:01 is associated with increased susceptibility to Goodpasture syndrome. Can present a self-peptide derived from COL4A3 (GWISLWKGFSF) on TCR (TRAV19 biased) in pathogenic CD4-positive T-helper 1 and T-helper 17 cells, triggering autoimmune inflammation. Rheumatoid arthritis (RA) [MIM:180300] An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB104:01; DRB104:04; DRB104:05; DRB104:08; DRB110:01; DRB101:01 and DRB1*01:02 are associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis). Variations at position 40 in the peptide-binding cleft of these alleles explain most of the association to rheumatoid arthritis risk.

Domain organisation. The beta-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the alpha-1 domain of HLA-DRA. Forms hydrogen bonds with the peptide main chain via conserved amino acid in most HLA-DRB molecules. The polymorphic residues accomodate the side chains of the peptide conferring peptide specificity to distinct HLA-DRB1 alleles. The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of TCR. The beta-2 Ig-like domain mediates the interaction with CD4 coreceptor.

Polymorphism. Highly polymorphic. Polymorphic residues encode for the beta-1 domain of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The sequence shown is that of DRB115:01. The sequences of common representative alleles of serologically distinct allele groups as defined in the catalog of common and well-documented HLA alleles, are described as variants of DRB115:01. In the context of hematological malignancy and T cell transplantation, alleles DRB103:01 and DRB113:01 present minor histocompatibility antigens derived respectively from host MTHFD1 and LY75 proteins, contributing to T cell-mediated graft-versus-leukemia effect and complete remission.

RefSeq proteins (1): NP_002115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000353	MHC_II_b_N	Domain
IPR003006	Ig/MHC_CS	Conserved_site
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014745	MHC_II_a/b_N	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050160	MHC/Immunoglobulin	Family

Pfam: PF00969, PF07654

UniProt features (134 total): sequence variant 85, strand 16, mutagenesis site 8, binding site 5, helix 5, turn 3, disulfide bond 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1, cross-link 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

108 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5NI9	X-RAY DIFFRACTION	1.33
4X5W	X-RAY DIFFRACTION	1.34
5NIG	X-RAY DIFFRACTION	1.35
8PJF	X-RAY DIFFRACTION	1.48
6QZC	X-RAY DIFFRACTION	1.64
4MD5	X-RAY DIFFRACTION	1.65
4MDJ	X-RAY DIFFRACTION	1.7
8PJE	X-RAY DIFFRACTION	1.7
8PJG	X-RAY DIFFRACTION	1.83
6R0E	X-RAY DIFFRACTION	1.91
1KLU	X-RAY DIFFRACTION	1.93
3PDO	X-RAY DIFFRACTION	1.95
4MD4	X-RAY DIFFRACTION	1.95
6HBY	X-RAY DIFFRACTION	1.95
5JLZ	X-RAY DIFFRACTION	1.99
1D5M	X-RAY DIFFRACTION	2
1D5Z	X-RAY DIFFRACTION	2
2G9H	X-RAY DIFFRACTION	2
4MDI	X-RAY DIFFRACTION	2
6CPN	X-RAY DIFFRACTION	2
6BIY	X-RAY DIFFRACTION	2.05
1PYW	X-RAY DIFFRACTION	2.1
3L6F	X-RAY DIFFRACTION	2.1
3S5L	X-RAY DIFFRACTION	2.1
5V4M	X-RAY DIFFRACTION	2.1
6BIJ	X-RAY DIFFRACTION	2.1
6BIZ	X-RAY DIFFRACTION	2.1
6NIX	X-RAY DIFFRACTION	2.1
4I5B	X-RAY DIFFRACTION	2.12
4MD0	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01911-F1	89.33	0.73

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 110; 111; 122; 86; 90

Post-translational modifications (1): 254

Disulfide bonds (2): 44–108, 146–202

Glycosylation sites (1): 48

Mutagenesis-validated functional residues (8):

Position	Phenotype
166	decreases the interaction with cd4; when associated with a-172.
172	decreases the interaction with cd4; when associated with a-166.
177	decreases the interaction with cd4.
181	reduces the interaction with hla-dm complex that results in impaired dissociation of clip from mhcii.
187	decreases the interaction with cd4.
213	reduces the interaction with hla-dm complex that results in impaired dissociation of clip from mhcii.
216	reduces the interaction with hla-dm complex that results in impaired dissociation of clip from mhcii.
254	impairs marchf1-dependent down-regulation through ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-202424	Downstream TCR signaling
R-HSA-202427	Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430	Translocation of ZAP-70 to Immunological synapse
R-HSA-202433	Generation of second messenger molecules
R-HSA-2132295	MHC class II antigen presentation
R-HSA-389948	Co-inhibition by PD-1
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 1126 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (41): positive regulation of T cell mediated cytotoxicity (GO:0001916), inflammatory response to antigenic stimulus (GO:0002437), myeloid dendritic cell antigen processing and presentation (GO:0002469), antigen processing and presentation of endogenous peptide antigen via MHC class II (GO:0002491), peptide antigen assembly with MHC class II protein complex (GO:0002503), positive regulation of T cell mediated immune response to tumor cell (GO:0002842), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), immune response (GO:0006955), humoral immune response (GO:0006959), signal transduction (GO:0007165), epidermis development (GO:0008544), detection of bacterium (GO:0016045), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), macrophage differentiation (GO:0030225), regulation of interleukin-10 production (GO:0032653), regulation of interleukin-4 production (GO:0032673), negative regulation of type II interferon production (GO:0032689), positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0032831), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), T-helper 1 type immune response (GO:0042088), negative regulation of T cell proliferation (GO:0042130), positive regulation of memory T cell differentiation (GO:0043382), regulation of T-helper cell differentiation (GO:0045622), positive regulation of monocyte differentiation (GO:0045657), positive regulation of immune response (GO:0050778), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell activation (GO:0050870), protein tetramerization (GO:0051262), positive regulation of CD4-positive, alpha-beta T cell activation (GO:2000516), positive regulation of protein phosphorylation (GO:0001934), adaptive immune response (GO:0002250), immune system process (GO:0002376), antigen processing and presentation of peptide or polysaccharide antigen via MHC class II (GO:0002504), cytoskeleton organization (GO:0007010), antigen processing and presentation (GO:0019882), positive regulation of kinase activity (GO:0033674), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of viral entry into host cell (GO:0046598)

GO Molecular Function (8): structural constituent of cytoskeleton (GO:0005200), MHC class II protein complex binding (GO:0023026), polysaccharide binding (GO:0030247), peptide antigen binding (GO:0042605), T cell receptor binding (GO:0042608), CD4 receptor binding (GO:0042609), protein binding (GO:0005515), MHC class II receptor activity (GO:0032395)

GO Cellular Component (25): Golgi membrane (GO:0000139), immunological synapse (GO:0001772), obsolete extracellular space (GO:0005615), lysosomal membrane (GO:0005765), intermediate filament (GO:0005882), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), transport vesicle membrane (GO:0030658), endocytic vesicle membrane (GO:0030666), clathrin-coated endocytic vesicle membrane (GO:0030669), late endosome membrane (GO:0031902), trans-Golgi network membrane (GO:0032588), MHC class II protein complex (GO:0042613), extracellular exosome (GO:0070062), lumenal side of endoplasmic reticulum membrane (GO:0098553), autolysosome membrane (GO:0120281), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endosome membrane (GO:0010008), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
TCR signaling	4
Adaptive Immune System	1
Regulation of T cell activation by CD28 family	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antigen processing and presentation of peptide antigen via MHC class II	3
bounding membrane of organelle	3
cellular anatomical structure	3
positive regulation of T cell mediated immunity	2
immune response	2
regulation of cytokine production	2
signaling receptor binding	2
plasma membrane	2
cytoplasmic vesicle membrane	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
inflammatory response	1
dendritic cell antigen processing and presentation	1
antigen processing and presentation of endogenous peptide antigen	1
MHC class II protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
T cell mediated immune response to tumor cell	1
positive regulation of immune response to tumor cell	1
regulation of T cell mediated immune response to tumor cell	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
tissue development	1
response to bacterium	1
detection of other organism	1
antigen processing and presentation of exogenous peptide antigen	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
interleukin-10 production	1
interleukin-4 production	1
negative regulation of cytokine production	1

Protein interactions and networks

STRING

3194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HLA-DRB1	HLA-DRA	P01903	968
HLA-DRB1	Q5Y7H0	Q5Y7H0	959
HLA-DRB1	PTPN22	Q9Y2R2	931
HLA-DRB1	CD4	P01730	879
HLA-DRB1	TNFRSF10A	O00220	868
HLA-DRB1	TNFRSF25	P78507	848
HLA-DRB1	TNF	P01375	825
HLA-DRB1	BTNL2	Q9UIR0	825
HLA-DRB1	IFNG	P01579	822
HLA-DRB1	HLA-DQA2	P01906	808
HLA-DRB1	MBP	P02686	780
HLA-DRB1	SLC26A3	P40879	769
HLA-DRB1	TOR1A	O14656	763
HLA-DRB1	CD8A	P01732	761
HLA-DRB1	HLA-DMA	P28067	761

IntAct

87 interactions, top by confidence:

A	B	Type	Score
HLA-DRA	HLA-DRB1	psi-mi:“MI:0914”(association)	0.880
HLA-DRA	HLA-DRB1	psi-mi:“MI:0407”(direct interaction)	0.880
HLA-DRB1	HLA-DRA	psi-mi:“MI:0407”(direct interaction)	0.880
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
HLA-DMA	HLA-DRA	psi-mi:“MI:0914”(association)	0.620
CD74	HLA-DRA	psi-mi:“MI:0914”(association)	0.560
hspa1a_hspa1b_human-1	HLA-DRB1	psi-mi:“MI:0407”(direct interaction)	0.540
hspa1a_hspa1b_human-1	HLA-DRB1	psi-mi:“MI:0915”(physical association)	0.540
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
HLA-DRB3	HLA-DRB1	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
HSPA8	HLA-DRB1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (167): HLA-DRB1 (Two-hybrid), HLA-DRB1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), PHOSPHO1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), EMC6 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS)

ESM2 similar proteins: C1ITJ8, O19477, P01901, P01902, P01911, P01915, P01920, P01921, P03991, P04230, P04231, P04440, P05538, P06341, P06342, P06343, P06344, P06345, P06346, P13599, P13762, P13765, P14428, P14483, P15464, P15979, P15982, P15983, P16391, P18211, P18467, P18468, P18469, P18470, P20040, P20756, P23068, P25311, P29826, P35737

Diamond homologs: A0A0G2K7V7, C1ITJ8, O19477, O35799, P01889, P01893, P01894, P01895, P01896, P01897, P01898, P01899, P01900, P01901, P01902, P01911, P01920, P03991, P04223, P04227, P04439, P04440, P05538, P06140, P06339, P10321, P13747, P13748, P13749, P13750, P13751, P13752, P13753, P13762, P14426, P14427, P14428, P14429, P14430, P14431

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CIITA	“up-regulates quantity by expression”	HLA-DRB1	“transcriptional regulation”
“EBV gH:gL:gp42”	“up-regulates activity”	HLA-DRB1	binding
HLA-DRB1	up-regulates	Membrane_fusion
“RFX complex”	“up-regulates quantity by expression”	HLA-DRB1	“transcriptional regulation”
VDR	“up-regulates quantity by expression”	HLA-DRB1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Interferon gamma signaling	8	21.8×	8e-07
ER-Phagosome pathway	5	14.1×	8e-04
Downstream TCR signaling	5	13.9×	8e-04
MHC class II antigen presentation	6	11.6×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptide antigen assembly with MHC class II protein complex	6	103.6×	3e-09
antigen processing and presentation of exogenous peptide antigen via MHC class II	7	62.4×	3e-09
positive regulation of immune response	6	47.4×	4e-07
positive regulation of T cell activation	6	43.6×	5e-07
positive regulation of T cell mediated cytotoxicity	5	41.9×	1e-05
T cell receptor signaling pathway	5	12.4×	2e-03
adaptive immune response	8	11.1×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

132 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	7
Likely benign	20
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1696856	NM_002124.4(HLA-DRB1):c.242A>T (p.Glu81Val)	Pathogenic
3065325	NM_002124.4(HLA-DRB1):c.764-2A>G	Likely pathogenic

SpliceAI

782 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32580740:CCTCA:C	donor_loss	1.0000
6:32580741:CTCA:C	donor_loss	1.0000
6:32580742:TCA:T	donor_loss	1.0000
6:32580743:CA:C	donor_loss	1.0000
6:32580744:A:AG	donor_loss	1.0000
6:32580745:C:CG	donor_loss	1.0000
6:32580745:CCTTT:C	donor_gain	1.0000
6:32580852:TGCTC:T	acceptor_gain	1.0000
6:32580854:CTC:C	acceptor_gain	1.0000
6:32580856:CCT:C	acceptor_loss	1.0000
6:32580857:C:CC	acceptor_gain	1.0000
6:32581555:A:AC	donor_gain	1.0000
6:32581555:ACT:A	donor_gain	1.0000
6:32581555:ACTC:A	donor_gain	1.0000
6:32581556:C:CC	donor_gain	1.0000
6:32581556:CT:C	donor_gain	1.0000
6:32581556:CTC:C	donor_gain	1.0000
6:32581556:CTCC:C	donor_gain	1.0000
6:32581558:C:CA	donor_gain	1.0000
6:32581839:C:CC	acceptor_gain	1.0000
6:32589641:A:AC	donor_gain	1.0000
6:32589642:C:CC	donor_gain	1.0000
6:32589642:CGT:C	donor_gain	1.0000
6:32579103:TC:T	acceptor_gain	0.9900
6:32579104:CC:C	acceptor_gain	0.9900
6:32579104:CCT:C	acceptor_loss	0.9900
6:32579105:C:CC	acceptor_gain	0.9900
6:32579105:CTGCA:C	acceptor_loss	0.9900
6:32579106:T:C	acceptor_loss	0.9900
6:32580245:A:AG	donor_loss	0.9900

AlphaMissense

1721 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32581756:G:C	F151L	0.989
6:32581756:G:T	F151L	0.989
6:32581758:A:G	F151L	0.989
6:32581657:G:C	F184L	0.975
6:32581657:G:T	F184L	0.975
6:32581659:A:G	F184L	0.975
6:32584272:G:C	F69L	0.973
6:32584272:G:T	F69L	0.973
6:32584274:A:G	F69L	0.973
6:32581772:C:G	C146S	0.962
6:32581773:A:T	C146S	0.962
6:32581558:C:A	W217C	0.960
6:32581558:C:G	W217C	0.960
6:32581731:A:G	W160R	0.958
6:32581731:A:T	W160R	0.958
6:32584156:C:G	C108S	0.954
6:32584157:A:T	C108S	0.954
6:32581604:C:G	C202S	0.951
6:32581605:A:T	C202S	0.951
6:32581773:A:G	C146R	0.950
6:32581591:G:C	H206Q	0.943
6:32581591:G:T	H206Q	0.943
6:32581757:A:C	F151C	0.943
6:32584251:G:C	F76L	0.942
6:32584251:G:T	F76L	0.942
6:32584253:A:G	F76L	0.942
6:32581771:G:C	C146W	0.941
6:32581772:C:T	C146Y	0.941
6:32581757:A:G	F151S	0.939
6:32584155:G:C	C108W	0.938

dbSNP variants (sampled 300 via entrez): RS1000965454 (6:32590534 G>A), RS1001163955 (6:32583614 T>C), RS1001512056 (6:32586212 C>A,G,T), RS1001913295 (6:32590027 T>G), RS1002948666 (6:32583596 A>G), RS1005031519 (6:32591470 A>G), RS1005364581 (6:32591308 T>A,C,G), RS1005609140 (6:32586940 T>G), RS1007014011 (6:32581232 T>C), RS1007785636 (6:32591765 T>C), RS1008494733 (6:32585875 C>T), RS1009685936 (6:32584512 C>A,G,T), RS1013880283 (6:32585449 A>G), RS1016199839 (6:32586049 T>A,C), RS1016321651 (6:32591327 T>A)

Disease associations

OMIM: gene MIM:142857 | disease phenotypes: MIM:181000, MIM:126200

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Supportive	Unknown

Mondo (4): sarcoidosis, susceptibility to, 1 (MONDO:0008399), multiple sclerosis, susceptibility to 1 (MONDO:0021571), multiple sclerosis, susceptibility to (MONDO:0007462), systemic lupus erythematosus (MONDO:0007915)

Orphanet (1): Sarcoidosis (Orphanet:797)

HPO phenotypes

306 total (30 of 306 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000017	Nocturia
HP:0000019	Urinary hesitancy
HP:0000020	Urinary incontinence
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000121	Nephrocalcinosis
HP:0000155	Oral ulcer
HP:0000206	Glossitis
HP:0000217	Xerostomia
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000433	Abnormal nasal mucosa morphology
HP:0000488	Retinopathy
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000502	Abnormal conjunctiva morphology
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000541	Retinal detachment
HP:0000554	Uveitis
HP:0000572	Visual loss
HP:0000597	Ophthalmoparesis
HP:0000613	Photophobia

GWAS associations

303 associations (top):

Study	Trait	p-value
GCST000040_4	Rheumatoid arthritis	8.000000e-27
GCST000054_4	Type 1 diabetes	1.000000e-16
GCST000070_2	Rheumatoid arthritis	1.000000e-108
GCST000206_1	Arthritis (juvenile idiopathic)	2.000000e-10
GCST000232_5	Rheumatoid arthritis	4.000000e-186
GCST000252_1	Multiple sclerosis	9.000000e-11
GCST000311_1	Ulcerative colitis	1.000000e-16
GCST000424_2	Multiple sclerosis	4.000000e-225
GCST000425_4	Multiple sclerosis	7.000000e-184
GCST000507_8	Systemic lupus erythematosus	1.000000e-12
GCST000677_3	Rheumatoid arthritis	2.000000e-58
GCST000735_1	Lumiracoxib-related liver injury	7.000000e-25
GCST000763_11	Immunoglobulin A	3.000000e-33
GCST000763_4	Immunoglobulin A	2.000000e-33
GCST000964_4	Ulcerative colitis	1.000000e-55
GCST001009_5	Nephropathy	2.000000e-26
GCST001022_3	Rheumatoid arthritis	5.000000e-23
GCST001043_1	Response to interferon beta therapy	4.000000e-10
GCST001118_1	Ulcerative colitis or Crohn’s disease	2.000000e-70
GCST001156_1	Systemic sclerosis	1.000000e-11
GCST001323_1	Nodular sclerosis Hodgkin lymphoma	8.000000e-18
GCST001323_2	Nodular sclerosis Hodgkin lymphoma	2.000000e-07
GCST001341_4	Multiple sclerosis	1.000000e-206
GCST001364_6	IgA nephropathy	4.000000e-20
GCST001474_7	Hypothyroidism	5.000000e-07
GCST001547_7	Immune response to anthrax vaccine	6.000000e-06
GCST001603_1	Hepatocellular carcinoma	5.000000e-22
GCST001728_3	Ulcerative colitis	5.000000e-133
GCST001757_10	Schizophrenia	5.000000e-06
GCST001785_9	Crohn’s disease	9.000000e-59

EFO canonical traits (52, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0004645	response to vaccine
EFO:0005206	oligoclonal band measurement
EFO:0006797	neurofibrillary tangles measurement
EFO:0006929	IgG index
EFO:0007017	peanut allergy measurement
EFO:0004881	asparaginase hypersensitivity
EFO:1001489	skin and soft tissue Staphylococcus aureus infection
EFO:0007790	Epstein Barr virus nuclear antigen 1 IgG measurement
EFO:0007791	rheumatoid factor seropositivity measurement
EFO:0007837	anti-citrullinated protein antibody seropositivity
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0007986	reticulocyte count
EFO:0004340	body mass index
EFO:0007796	parental longevity
EFO:0008402	susceptibility to cold sores measurement
EFO:0008401	susceptibility to shingles measurement
EFO:0008406	susceptibility to plantar warts measurement
EFO:0008407	susceptibility to Mycobacterium tuberculosis infection measurement
EFO:0008409	susceptibility to scarlet fever measurement
EFO:0008410	susceptibility to pneumonia measurement
EFO:0008412	susceptibility to vaginal yeast infection measurement
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0009184	heart rate response to exercise
EFO:0006941	grip strength measurement
EFO:0004570	bilirubin measurement
EFO:0004587	lymphocyte count
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831291 (SINGLE PROTEIN), CHEMBL3988561 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

28 annotations.

Variant	Type	Level	Drugs	Phenotypes
HLA-DRB1*01:01	Toxicity	2B	nevirapine
HLA-DRB101:01, HLA-DRB104:06	Toxicity	3	atorvastatin;fluvastatin;HMG-CoA reductase inhibitors;pravastatin;rosuvastatin;simvastatin
HLA-DRB1*01:02	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-DRB1*01:03	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-DRB1*03:01	Toxicity	3	allopurinol	Severe Cutaneous Adverse Reactions
HLA-DRB1*03:01	Toxicity	3	carbamazepine	Maculopapular Exanthema
HLA-DRB103:01, HLA-DRB104:04	Toxicity	3	infliximab	Drug-induced liver injury
HLA-DRB1*04:01	Efficacy	3	interferon beta-1a	Multiple Sclerosis
HLA-DRB1*04:02	Toxicity	3	clozapine	Agranulocytosis
HLA-DRB1*04:03	Toxicity	3	oxcarbazepine	Epilepsy
HLA-DRB1*04:04	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-DRB1*07:01	Toxicity	3	azathioprine;mercaptopurine	Drug Toxicity;Inflammatory Bowel Diseases;Pancreatitis
HLA-DRB1*07:01	Toxicity	3	pegaspargase
HLA-DRB1*07:01	Toxicity	3	lapatinib	Toxic liver disease
HLA-DRB1*08:01	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-DRB1*08:03	Toxicity	3	Antithyroid Preparations	Agranulocytosis;Graves Disease
HLA-DRB1*09:01	Toxicity	3	allopurinol	Drug Hypersensitivity
HLA-DRB1*10:01	Toxicity	3	nevirapine	Drug Reaction with Eosinophilia and Systemic Symptoms;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-DRB1*11:01	Toxicity	3	Antiinflammatory agents;non-steroids	Anaphylaxis
HLA-DRB1*13:02	Toxicity	3	allopurinol	Severe Cutaneous Adverse Reactions
HLA-DRB1*14:01	Toxicity	3	allopurinol	Drug Hypersensitivity
HLA-DRB115:01, HLA-DRB116:02	Toxicity	3	dapsone	Drug Hypersensitivity
HLA-DRB1*15:02	Toxicity	3	allopurinol	Severe Cutaneous Adverse Reactions
HLA-DRB1*16:01	Toxicity	3	flupirtine	Drug-induced liver injury
rs17211071	Toxicity	3	dapsone	Drug Hypersensitivity
rs17885382	Toxicity	3	asparaginase	Acute lymphoblastic leukemia
rs201929247	Toxicity	3	dapsone	Drug Hypersensitivity
rs701829	Toxicity	3	dapsone	Drug Hypersensitivity

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17885382	HLA-DRB1	3	3.00	1	asparaginase
rs201929247	HLA-DRB1	3	3.00	1	dapsone
rs701829	HLA-DRB1	3	3.00	1	dapsone
rs17211071	HLA-DRB1	3	3.00	1	dapsone

ChEMBL bioactivities

81 potent at pChembl≥5 of 95 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CHEMBL1253324
8.85	IC50	1.4	nM	CHEMBL292340
8.85	IC50	1.4	nM	CHEMBL79117
8.40	IC50	4	nM	CHEMBL1253322
8.40	IC50	4	nM	CHEMBL1253325
8.28	IC50	5.3	nM	CHEMBL421516
8.19	IC50	6.5	nM	CHEMBL75687
8.00	IC50	9.9	nM	CHEMBL79117
7.96	IC50	11	nM	CHEMBL1253323
7.94	IC50	11.5	nM	CHEMBL1253323
7.92	IC50	12	nM	CHEMBL311245
7.89	IC50	13	nM	CHEMBL4284706
7.89	IC50	13	nM	CHEMBL4277461
7.80	IC50	16	nM	CHEMBL80447
7.77	IC50	17	nM	CHEMBL292340
7.77	IC50	17	nM	CHEMBL80597
7.72	IC50	19	nM	CHEMBL77558
7.66	IC50	22	nM	CHEMBL81463
7.64	IC50	23	nM	CHEMBL79058
7.60	IC50	25	nM	CHEMBL80852
7.57	IC50	27	nM	CHEMBL1253321
7.55	IC50	28	nM	CHEMBL78426
7.55	IC50	28	nM	CHEMBL1253327
7.51	IC50	31	nM	CHEMBL312367
7.50	IC50	32	nM	CHEMBL420761
7.46	IC50	35	nM	CHEMBL421516
7.37	IC50	43	nM	CHEMBL80345
7.34	IC50	46	nM	CHEMBL310163
7.34	IC50	46	nM	CHEMBL309641
7.25	IC50	56	nM	CHEMBL4292594
7.20	IC50	63	nM	CHEMBL75687
7.17	IC50	67	nM	CHEMBL310312
7.14	IC50	73	nM	CHEMBL77558
7.12	IC50	75	nM	CHEMBL80597
7.09	IC50	81	nM	CHEMBL310625
7.09	IC50	81	nM	CHEMBL78541
7.09	IC50	82	nM	CHEMBL311245
7.07	IC50	85	nM	CHEMBL79058
7.06	IC50	87	nM	CHEMBL4277461
6.85	IC50	140	nM	CHEMBL76898
6.85	IC50	140	nM	CHEMBL80447
6.85	IC50	140	nM	CHEMBL309610
6.80	IC50	160	nM	CHEMBL311939
6.77	IC50	170	nM	CHEMBL420380
6.75	IC50	180	nM	CHEMBL309641
6.70	IC50	200	nM	CHEMBL79025
6.64	IC50	230	nM	CHEMBL80176
6.62	IC50	240	nM	CHEMBL80527
6.57	IC50	270	nM	CHEMBL80563
6.54	IC50	290	nM	CHEMBL81463

PubChem BioAssay actives

14 with measured affinity, of 32 total; 9 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-amino-3-[5-(dimethylamino)-1,3-dioxoisoindol-2-yl]propanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxybutanoic acid	513612: Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells by ELISA	ic50	0.0006	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-[5-(dimethylamino)-1,3-dioxoisoindol-2-yl]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	513612: Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells by ELISA	ic50	0.0040	uM
(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxybutanoic acid	513612: Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells by ELISA	ic50	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-[6-(dimethylamino)-1,3-dioxobenzo[f]isoindol-2-yl]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	513624: Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells at acidic pH by ELISA	ic50	0.0110	uM
(4S)-4-amino-5-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[(2S)-2-[[(1S)-1-carboxy-4-(diaminomethylideneamino)butyl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-5-oxopentanoic acid	1402036: Inhibition of biotin-labeled MBP (85 to 99 residues) binding to HLA class 2 DRB1*1501 mutant allele after 2 hrs by TMB + substrate-chromogen based assay	ic50	0.0130	uM
(4S)-5-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[(2S)-2-[[(1S)-1-carboxy-4-(diaminomethylideneamino)butyl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-4-(6-aminohexanoylamino)-5-oxopentanoic acid	1402036: Inhibition of biotin-labeled MBP (85 to 99 residues) binding to HLA class 2 DRB1*1501 mutant allele after 2 hrs by TMB + substrate-chromogen based assay	ic50	0.0130	uM
3-[[(2S)-2-acetamido-3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-oxopropyl]carbamoyl]-6-(dimethylamino)naphthalene-2-carboxylic acid	513624: Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells at acidic pH by ELISA	ic50	0.0270	uM
2-[2-[[(2S)-2-acetamido-3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-oxopropyl]amino]-2-oxoethyl]-5-(dimethylamino)benzoic acid	513624: Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells at acidic pH by ELISA	ic50	0.0280	uM
(4S)-5-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-4-[6-[3-[[2-[4-[(4-hydroxy-9,10-dioxoanthracen-1-yl)amino]butylamino]-2-oxoethyl]disulfanyl]propanoylamino]hexanoylamino]-5-oxopentanoic acid	1402036: Inhibition of biotin-labeled MBP (85 to 99 residues) binding to HLA class 2 DRB1*1501 mutant allele after 2 hrs by TMB + substrate-chromogen based assay	ic50	0.0560	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
beryllium sulfate	increases expression, increases response to substance	2
Arsenic	affects expression	2
Estradiol	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Lead	affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression	2
Cyclosporine	decreases expression	2
Antirheumatic Agents	decreases expression	2
perfluorotetradecanoic acid	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	decreases expression	1
nickel chloride	affects cotreatment, increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorobutyric acid	increases expression	1
lumiracoxib	affects response to substance	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Celecoxib	affects expression	1
Irinotecan	increases expression	1
Gefitinib	affects expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cefepime	affects expression	1
Acetaminophen	decreases expression	1
Allergens	affects cotreatment, increases expression	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1252964	Binding	Displacement of biotin-HA from recombinant soluble HLA-DR1 expressed in human T2 cells by ELISA	Fluorogenic probes for monitoring peptide binding to class II MHC proteins in living cells. — Nat Chem Biol

Cellosaurus cell lines

9 cell lines: 4 hybrid cell line, 3 spontaneously immortalized cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9W15	T2.DR4	Hybrid cell line
CVCL_9W16	T2.DR4/DM	Hybrid cell line
CVCL_9W17	T2.DR3	Hybrid cell line
CVCL_9W18	T2.DR3/DM	Hybrid cell line
CVCL_9W22	BLS-1.DR4	Transformed cell line	Male
CVCL_9W23	BLS-1.DR5	Transformed cell line	Male
CVCL_V069	DAP.3-DR1	Spontaneously immortalized cell line	Male
CVCL_V070	DAP.3-DR4	Spontaneously immortalized cell line	Male
CVCL_V120	LDR2b	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

521 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients