HLA-DPB1

Summary

HLA-DPB1 (major histocompatibility complex, class II, DP beta 1, HGNC:4940) is a protein-coding gene on chromosome 6p21.32, encoding HLA class II histocompatibility antigen, DP beta 1 chain (P04440). Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.

HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), 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 (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 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 DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules.

Source: NCBI Gene 3115 — RefSeq curated summary.

At a glance

• GWAS associations: 52
• Clinical variants (ClinVar): 33 total
• Phenotypes (HPO): 94
• MANE Select transcript: NM_002121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4940
Approved symbol	HLA-DPB1
Name	major histocompatibility complex, class II, DP beta 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000223865
Ensembl biotype	protein_coding
OMIM	142858
Entrez	3115

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000416804, ENST00000418931, ENST00000428835, ENST00000469120, ENST00000471184, ENST00000478189, ENST00000498038, ENST00000714454, ENST00000714455, ENST00000714456, ENST00000714457, ENST00000907475, ENST00000907476, ENST00000907477, ENST00000907478, ENST00000966802, ENST00000966803, ENST00000966804

RefSeq mRNA: 1 — MANE Select: NM_002121 NM_002121

CCDS: CCDS4765

Canonical transcript exons

ENST00000383102 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 138.7383 / max 12395.6436, expressed in 1294 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67227	133.5418	634
67229	2.7846	887
67230	1.6328	773
67228	0.5713	367
67234	0.1254	68
67233	0.0824	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.59	gold quality
lymph node	UBERON:0000029	99.50	gold quality
vermiform appendix	UBERON:0001154	99.48	gold quality
leukocyte	CL:0000738	99.38	gold quality
monocyte	CL:0000576	99.37	gold quality
gall bladder	UBERON:0002110	99.32	gold quality
spleen	UBERON:0002106	99.23	gold quality
upper lobe of left lung	UBERON:0008952	98.85	gold quality
right lung	UBERON:0002167	98.78	gold quality
duodenum	UBERON:0002114	98.68	gold quality
right coronary artery	UBERON:0001625	98.62	gold quality
rectum	UBERON:0001052	97.88	gold quality
smooth muscle tissue	UBERON:0001135	97.77	gold quality
tibial nerve	UBERON:0001323	97.66	gold quality
descending thoracic aorta	UBERON:0002345	97.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.40	gold quality
blood	UBERON:0000178	97.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.16	gold quality
spinal cord	UBERON:0002240	97.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.06	gold quality
small intestine	UBERON:0002108	96.94	gold quality
adipose tissue	UBERON:0001013	96.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.73	gold quality
thoracic mammary gland	UBERON:0005200	96.69	gold quality
thoracic aorta	UBERON:0001515	96.67	gold quality
left coronary artery	UBERON:0001626	96.66	gold quality
ascending aorta	UBERON:0001496	96.60	gold quality
fallopian tube	UBERON:0003889	96.34	gold quality
omental fat pad	UBERON:0010414	96.21	gold quality
lung	UBERON:0002048	96.15	gold quality

Single-cell (SCXA)

Detected in 41 experiment(s), a significant marker in 37.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	10073.08
E-CURD-126	yes	8687.23
E-MTAB-10553	yes	8324.01
E-HCAD-1	yes	5241.86
E-MTAB-8322	yes	4431.13
E-MTAB-8410	yes	3926.64
E-MTAB-6701	yes	3393.97
E-MTAB-6653	yes	3353.87
E-MTAB-10287	yes	2836.14
E-HCAD-36	yes	2735.87
E-GEOD-139324	yes	2673.42
E-MTAB-6308	yes	2574.15
E-GEOD-149689	yes	2411.50
E-MTAB-9435	yes	1822.36
E-HCAD-38	yes	1765.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CIITA, RFX1, RFX5, RFXANK, RFXAP

miRNA regulators (miRDB)

114 targeting HLA-DPB1, 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-4692	100.00	67.32	2066
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4699-3P	99.71	70.15	3142

Literature-anchored findings (GeneRIF, showing 40)

• Identification of a novel HLA-DPB1 allele, DPB1*02014. (PMID:11972883)
• Analysis of the role of DPB1-encoded amino acids in the genetic predisposition to type I diabetes mellitus (PMID:11975985)
• Family studies revealed significant linkage disequilibrium between the RXRB alleles and a number of HLA-DPB1 alleles. (PMID:12175732)
• existence of a specific trans-acting factor involved in the control of DPB1 gene expression. (PMID:12542744)
• Polymorphism of HLA-DRB1, DQB1 and DPB1 in unrelated healthy volunteers from the Naxi ethnic group. The distribution characteristics of the HLA class II alleles revealed that the Naxi ethnic group belonged to the Southern group of Chinese. (PMID:12694588)
• Donor/recipient DPB1 match was associated with a significantly lower incidence of acute graft vs host diseae and a higher incidence of disease relapse. (PMID:12774051)
• Dravidian-speaking castes of southern India were typed for polymorphism at this allele. (PMID:12823769)
• It is concluded that positive association may exist between certain HLA-DPB1 alleles and CML. (PMID:12844410)
• It is likely that familial aggregation of IDDM is associated with lower frequency of protective alleles of HLA-DQB1 gene. (PMID:12878786)
• HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for hematologic stem cell transplantation. (PMID:14576061)
• HLA-DPB1 Glu69 is found to be a marker of beryllium sensitization and not specific for disease; Glu69 homozygosity acts as a functional marker associated with markers of chronic beryllium disease severity. (PMID:14662898)
• HLA association in aspirin-intolerant asthma: DPB1*0301 as a strong marker in a Korean population. (PMID:15007363)
• ALLELES OF THE HLA DQB1 GENE HAVE BEEN SHOWN TO BE ASSOCIATED WITH DIABETES MELLITUS TYPE 1 IN STUDIES FROM MANY GEOGRAPHIC LOCATIONS. (P.298) (PMID:15112906)
• DPB1 associations, especially the DPB1*0301 allele, with type 1 diabetes. (PMID:15277401)
• high genetic affinity between the Basque samples (North Navarre and Guipuzcoa), which, in turn, tend to plot separately from the remaining European populations. (PMID:15304007)
• Evidence is provided that that the extended haplotype of HLA-DPB1 is distinct in pauciarticular and polyarticular rheumatoid factor negative juvenile idiopathic arthritis patients. (PMID:15343265)
• a significant association between Leukotriene receptor antagonists (LTRA) responsiveness and an HLA-DPB1*0301 allele in long term management of a patients with Aspirin-intolerant asthma (PMID:15446291)
• analysis of polymorphisms in HLA-DRB1, HLA-DQB1, and HLA-DPB1 genes in the Shandong Han population (PMID:15982255)
• analysis of novel allele HLA-DPB1*0302 (PMID:15982263)
• HLA class I and class II genes do not contribute to susceptibility to HAU. (PMID:16019679)
• sequence of exon 2 of HLA-DPB1*0403 (PMID:16147881)
• In DPB1 mismatch in the host versus graft reaciont, risk of rejection was significantly increased in stem cell transplantation. (PMID:16317094)
• HLA class II antigen loss was significantly correlated with glioblastoma multiforme (PMID:16322289)
• In the 13 DPB1 alleles detected, the most frequent allele was DPB1*0501 in Miao and Yao followed by DPB1*02 and DPB1*1301. (PMID:16441488)
• The ability of MHC class II to modulate activation of the pro-apoptotic receptor Fas by blocking the accessory molecule FADD and to delay apoptosis induction could allow for cytokine secretion by H pylori-infected gastric epithelial cells. (PMID:16937440)
• TNF-alpha promoter polymorphism may significantly increase susceptibility to aspirin-intolerant asthma by gene-to-gene interaction with HLA DPB1*0301 (PMID:17014432)
• DPB1*1902 allele identified; resulted from a single-nucleotide substitution at codon 35 (TTC –> CTC/F –> L) of exon 2 of DPB1*0402 or 0602 (PMID:17493157)
• Children with DRB1*0401 (the most common DRB1*04 subtype), DPB1*0402 influences development of anti-islet autoantibodies and decreases risk of type 1 diabetes. (PMID:17513705)
• DPB1*0101 may afford protection from the development of fusion gene TEL-AML1+ and high hyperdiploid childhood B cell precursor acute lymphoblastic leukaemia (PMID:17622527)
• T cell epitope (TCE), is abrogated by the presence of amino acids LFQG in positions 8-11 of the DP beta-chain; DPB1 TCE disparities may hamper the clinical success of transplants when DPB1 matching is not included into the donor selection criteria (PMID:17697965)
• The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. (PMID:17726164)
• in acute lymphocytic leukemia, DPB1-matched pairs had a significantly worse overall survival (PMID:17964196)
• HLA-DPB1 can mediate alloreactive responses and HLA-DPB1 mismatch increases the risk of aGVHD in sibling donor stem cell transplantation. (PMID:17977207)
• Mycosis fungoides in siblings with specific haplotype in HLA-DQB1 are described. (HLA-DQB1*03,*03 in the girl, HLA-DQB1*02,*03 in the boy) (PMID:17989893)
• These results implied that the HLA-DP molecules with specificity pocket appropriate for HCV antigen(s) might confer the progressive process of hypertrophic cardiomyopathy among the HCV-infected individuals. (PMID:18186799)
• Risk of type I diabetes in individuals with extended DR3 haplotype 8.1 is genotype-dependent, possibly associated with DPB1 and HLA class I loci (PMID:18486765)
• DPB1*1501 may be associated with protection against pulmonary tuberculosis development both in HIV positive and negative subjects (PMID:18652916)
• The comparison of HLA class II allele frequencies of Bais with those of other Chinese populations suggested that the Bai ethnic group belonged to the southern group of Chinese. (PMID:18778327)
• Of 55 AA substituions at 19 positions, none were associated with a decreased risk of relapse in hematologic neoplasm patients treated with HSCT. Tyr9C-Ser9C & Tyr99C-Phe99C were strongly linked. (PMID:18997170)
• the emergence of anti-AQP4 antibody is reinforced by the presence of the HLA-DPB1*0501 allele in Japanese. (PMID:19140826)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	RT1-Hb-ps1	ENSRNOG00000061936

Paralogs (13): B2M (ENSG00000166710), HLA-DQB1 (ENSG00000179344), HLA-DRB1 (ENSG00000196126), HLA-DQA1 (ENSG00000196735), HLA-DRB5 (ENSG00000198502), HLA-DOA (ENSG00000204252), HLA-DMA (ENSG00000204257), HLA-DRA (ENSG00000204287), HLA-DPA1 (ENSG00000231389), HLA-DQB2 (ENSG00000232629), HLA-DQA2 (ENSG00000237541), HLA-DOB (ENSG00000241106), HLA-DMB (ENSG00000242574)

Protein

Protein identifiers

HLA class II histocompatibility antigen, DP beta 1 chain — P04440 (reviewed: P04440)

Alternative names: HLA class II histocompatibility antigen, DP(W4) beta chain, MHC class II antigen DPB1

All UniProt accessions (7): P04440, A0AAQ5BI07, A0AAQ5BI18, A0AAQ5BI78, H0Y5P2, H0Y7G7, I4EC15

UniProt curated annotations — full annotation on UniProt →

Function. Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

Subunit / interactions. Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus. trans-Golgi network membrane. Endosome membrane. Lysosome membrane.

Polymorphism. The following alleles of HLA-DPB1 are known: DPB101:01, DPB101:02, DPB102:01, DPB102:02, DPB102:03, DPB103:01, DPB103:02, DPB104:01, DPB104:02, DPB104:03, DPB105:01, DPB105:02, DPB106:01, DPB106:02, DPB108:01, DPB108:02, DPB109:01, DPB109:02, DPB110:01, DPB110:02, DPB111:01, DPB111:02, DPB113:01, DPB113:02, DPB114:01, DPB114:02, DPB115:01, DPB115:02, DPB116:01, DPB116:02, DPB117:01, DPB117:02, DPB118:01, DPB118:02, DPB119:01, DPB119:02, DPB120:01, DPB120:02, DPB121:01, DPB121:02, DPB122:01, DPB122:02, DPB123:01, DPB124:01, DPB124:02, DPB125:01, DPB125:02, DPB126:01, DPB126:02, DPB127:01, DPB128:01, DPB129:01, DPB130:01, DPB131:01, DPB132:01, DPB133:01, DPB134:01, DPB135:01, DPB136:01, DPB137:01, DPB138:01, DPB139:01, DPB140:01, DPB141:01, DPB144:01, DPB145:01, DPB146:01, DPB147:01, DPB148:01, DPB149:01, DPB150:01, DPB151:01, DPB152:01, DPB153:01, DPB154:01, DPB155:01, DPB156:01, DPB157:01, DPB158:01, DPB159:01, DPB160:01, DPB162:01, DPB163:01, DPB165:01, DPB166:01, DPB167:01, DPB168:01, DPB169:01, DPB170:01, DPB171:01, DPB172:01, DPB173:01, DPB174:01, DPB175:01, DPB176:01, DPB177:01, DPB178:01, DPB179:01, DPB180:01, DPB181:01, DPB182:01, DPB183:01, DPB184:01, DPB185:01, DPB186:01, DPB187:01, DPB188:01, DPB189:01, DPB190:01, DPB191:01, DPB192:01, DPB193:01, DPB194:01, DPB195:01, DPB196:01, DPB197:01, DPB198:01 and DPB199:01. The sequence shown is that of DPB1*04:01.

Similarity. Belongs to the MHC class II family.

RefSeq proteins (1): NP_002112* (*=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 (89 total): sequence variant 56, strand 13, helix 6, region of interest 3, disulfide bond 2, topological domain 2, turn 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4P5M	X-RAY DIFFRACTION	1.7
4P5K	X-RAY DIFFRACTION	2.59
4P57	X-RAY DIFFRACTION	2.6
4P4K	X-RAY DIFFRACTION	2.8
7T2B	X-RAY DIFFRACTION	2.8
4P4R	X-RAY DIFFRACTION	3
7T2A	X-RAY DIFFRACTION	3.04
7T2C	X-RAY DIFFRACTION	3.1
3LQZ	X-RAY DIFFRACTION	3.25
7T2D	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04440-F1	88.20	0.68

Functional residue map

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

Disulfide bonds (2): 44–106, 144–200

Glycosylation sites (1): 48

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: 510 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, BROWNE_HCMV_INFECTION_16HR_UP, GAURNIER_PSMD4_TARGETS, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN

GO Biological Process (12): adaptive immune response (GO:0002250), peptide antigen assembly with MHC class II protein complex (GO:0002503), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), positive regulation of type II interferon production (GO:0032729), positive regulation of T cell proliferation (GO:0042102), positive regulation of immune response (GO:0050778), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell activation (GO:0050870), immune system process (GO:0002376), antigen processing and presentation of peptide or polysaccharide antigen via MHC class II (GO:0002504), immune response (GO:0006955), antigen processing and presentation (GO:0019882)

GO Molecular Function (3): MHC class II protein complex binding (GO:0023026), peptide antigen binding (GO:0042605), protein binding (GO:0005515)

GO Cellular Component (19): Golgi membrane (GO:0000139), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), 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), lumenal side of endoplasmic reticulum membrane (GO:0098553), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), endosome membrane (GO:0010008)

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
bounding membrane of organelle	4
cytoplasmic vesicle membrane	3
endomembrane system	3
immune response	2
antigen processing and presentation of peptide antigen via MHC class II	2
immune system process	2
cellular anatomical structure	2
organelle membrane	2
cytoplasm	2
intracellular membrane-bounded organelle	2
MHC class II protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
antigen processing and presentation of exogenous peptide antigen	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
positive regulation of immune system process	1
positive regulation of response to stimulus	1
regulation of immune response	1
antigen receptor-mediated signaling pathway	1
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1
biological_process	1
antigen processing and presentation	1
response to stimulus	1
MHC protein complex binding	1
antigen binding	1
peptide binding	1
binding	1
Golgi apparatus	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

44 interactions, top by confidence:

A	B	Type	Score
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
HLA-DPB1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
HLA-DPB1	OPTN	psi-mi:“MI:0915”(physical association)	0.560
CD74	HLA-DRA	psi-mi:“MI:0914”(association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
HLA-DPB1	IDE	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
AHSG	HLA-DPB1	psi-mi:“MI:0915”(physical association)	0.400
COPB1	HLA-DPB1	psi-mi:“MI:0915”(physical association)	0.370
ROBO2	HLA-DPB1	psi-mi:“MI:0915”(physical association)	0.370
HLA-DPB1	RTN4	psi-mi:“MI:0915”(physical association)	0.370
CD74		psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NRG1	HS6ST1	psi-mi:“MI:0914”(association)	0.350
GCNT2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
EXT2	ATE1	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TAPBP	psi-mi:“MI:0914”(association)	0.350
SPCS3	XRCC3	psi-mi:“MI:0914”(association)	0.350
FKBP2	HLA-DQA1	psi-mi:“MI:0914”(association)	0.350
RARRES2	HLA-DPB1	psi-mi:“MI:0914”(association)	0.350
FSTL1	HLA-DPB1	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	YPEL5	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (116): TRIP6 (Two-hybrid), LZTS2 (Two-hybrid), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS)

ESM2 similar proteins: C1ITJ8, O19477, O35799, P01901, P01902, P01920, P01921, P04440, P05538, P06339, P06341, P06342, P06343, P06344, P06345, P06346, P13765, P14428, P14429, P14432, P14483, P15464, P15979, P15982, P15983, P16391, P18467, P18469, P18470, P23068, P25311, P29826, P60018, P70387, Q29980, Q29983, Q2KN22, Q30201, Q5RD09, Q63678

Diamond homologs: A0A5B9, A0M8Q6, B9A064, P01834, P01835, P01836, P01837, P01838, P01839, P01840, P01841, P01843, P01844, P01845, P01846, P01847, P01850, P01851, P01852, P01854, P01855, P01857, P01859, P01860, P01861, P01862, P01863, P01865, P01867, P01868, P01869, P01871, P01872, P01874, P01921, P03984, P03987, P03988, P04221, P04230

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CIITA	“up-regulates quantity by expression”	HLA-DPB1	“transcriptional regulation”
“RFX complex”	“up-regulates quantity by expression”	HLA-DPB1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1123 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33076138:CCAGG:C	donor_loss	1.0000
6:33076139:CAGGT:C	donor_loss	1.0000
6:33076140:AGGT:A	donor_loss	1.0000
6:33076141:GGT:G	donor_loss	1.0000
6:33076143:T:A	donor_loss	1.0000
6:33080936:G:GA	donor_loss	1.0000
6:33080937:T:G	donor_loss	1.0000
6:33084948:A:AG	acceptor_gain	1.0000
6:33084949:G:GG	acceptor_gain	1.0000
6:33085168:G:GT	donor_gain	1.0000
6:33085227:GTGGA:G	donor_gain	1.0000
6:33085228:TGGA:T	donor_gain	1.0000
6:33085228:TGGAG:T	donor_loss	1.0000
6:33085229:GGA:G	donor_gain	1.0000
6:33085229:GGAG:G	donor_gain	1.0000
6:33085230:GA:G	donor_gain	1.0000
6:33085230:GAG:G	donor_gain	1.0000
6:33085231:AGTG:A	donor_loss	1.0000
6:33085232:G:GG	donor_gain	1.0000
6:33085232:GT:G	donor_loss	1.0000
6:33085233:T:G	donor_loss	1.0000
6:33085777:A:AG	acceptor_gain	1.0000
6:33085778:G:GG	acceptor_gain	1.0000
6:33085778:GA:G	acceptor_gain	1.0000
6:33085885:GAAAG:G	donor_gain	1.0000
6:33085887:AAG:A	donor_loss	1.0000
6:33085888:AG:A	donor_loss	1.0000
6:33085889:GG:G	donor_loss	1.0000
6:33086212:A:AG	acceptor_gain	1.0000
6:33086217:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000127410 (6:33078551 A>C), RS1000254634 (6:33087415 T>G), RS1000357828 (6:33076538 C>T), RS1000705128 (6:33087974 T>A,C), RS1000958471 (6:33075239 C>T), RS1001307177 (6:33074991 T>G), RS1001414936 (6:33083104 A>G), RS1001466897 (6:33083348 A>G), RS1001630799 (6:33077606 G>A,C), RS1002105185 (6:33087139 A>G), RS1002322874 (6:33089253 T>C), RS1002327053 (6:33082602 G>A), RS1002417445 (6:33081712 T>G), RS1002545086 (6:33086147 A>G), RS1002923803 (6:33081621 G>A)

Disease associations

OMIM: gene MIM:142858 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000024	Prostatitis
HP:0000071	Ureteral stenosis
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000126	Hydronephrosis
HP:0000163	Abnormal oral cavity morphology
HP:0000246	Sinusitis
HP:0000366	Abnormality of the nose
HP:0000388	Otitis media
HP:0000389	Chronic otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000488	Retinopathy
HP:0000491	Keratitis
HP:0000505	Visual impairment
HP:0000520	Proptosis
HP:0000579	Nasolacrimal duct obstruction
HP:0000763	Sensory neuropathy
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0000873	Diabetes insipidus
HP:0000979	Purpura
HP:0000988	Skin rash
HP:0001250	Seizure
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001607	Subglottic stenosis
HP:0001681	Angina pectoris

GWAS associations

52 associations (top):

Study	Trait	p-value
GCST000375_1	Hepatitis B	6.000000e-39
GCST001009_1	Nephropathy	5.000000e-09
GCST001150_3	Hepatitis B	3.000000e-54
GCST001156_12	Systemic sclerosis	2.000000e-20
GCST001162_2	Hepatitis B vaccine response	3.000000e-12
GCST001582_2	Hepatitis B (viral clearance)	2.000000e-17
GCST001582_4	Hepatitis B (viral clearance)	2.000000e-21
GCST001747_1	Aspirin exacerbated respiratory disease in asthmatics	5.000000e-07
GCST002160_5	Wegener’s granulomatosis	2.000000e-50
GCST002217_5	Sjögren’s syndrome	9.000000e-25
GCST002490_3	Chronic hepatitis B infection	5.000000e-14
GCST002490_5	Chronic hepatitis B infection	1.000000e-12
GCST002655_14	IgA nephropathy	5.000000e-07
GCST002655_17	IgA nephropathy	5.000000e-07
GCST002655_23	IgA nephropathy	2.000000e-11
GCST002879_10	Chronic hepatitis B infection	1.000000e-70
GCST003092_7	Myositis	4.000000e-21
GCST003522_1	Dermatomyositis	1.000000e-09
GCST003522_4	Dermatomyositis	3.000000e-10
GCST003605_2	EGFR mutation-positive lung adenocarcinoma	5.000000e-17
GCST003615_2	Persistent hepatitis B virus infection	4.000000e-06
GCST003941_2	Acute graft versus host disease in bone marrow transplantation (recipient effect)	2.000000e-09
GCST003976_2	Antineutrophil cytoplasmic antibody-associated vasculitis	1.000000e-89
GCST004062_2	Sjögren’s syndrome	3.000000e-07
GCST004110_14	Gait speed in old age	3.000000e-07
GCST004302_2	Primary biliary cholangitis	2.000000e-22
GCST004521_255	Autism spectrum disorder or schizophrenia	6.000000e-11
GCST004600_125	Eosinophil percentage of white cells	2.000000e-17
GCST004617_25	Eosinophil percentage of granulocytes	7.000000e-15
GCST004625_31	Monocyte count	3.000000e-12

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004599	acute graft vs. host disease
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005091	monocyte count
EFO:0008406	susceptibility to plantar warts measurement
EFO:0009180	rosacea severity measurement
EFO:0009357	Anti-rubella virus IgG measurement
EFO:0009358	Anti-hepatitis B virus surface antigen IgG measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0006927	severe aplastic anemia
EFO:0008405	susceptibility to hepatitis B infection measurement
EFO:0004833	neutrophil count
EFO:0004736	aspartate aminotransferase measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
HLA-DPB1*03:01	Toxicity	2B	aspirin	Asthma
HLA-DPB1*04:01	Toxicity	3	aspirin	Asthma
HLA-DPB1*10:01	Toxicity	3	infliximab	Drug-induced liver injury
rs1042136	Toxicity	3	aspirin	Aspirin-induced asthma;Asthma
rs1042151	Toxicity	3	aspirin	Aspirin-induced asthma;Asthma
rs3097671	Toxicity	3	aspirin	Aspirin-induced asthma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1042136	HLA-DPA1, HLA-DPB1	3	3.00	1	aspirin
rs1042151	HLA-DPA1, HLA-DPB1	3	0.00	1	aspirin
rs3097671	HLA-DPA1, HLA-DPB1	3	0.00	1	aspirin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Beryllium	increases response to substance, affects binding	3
Valproic Acid	affects expression, increases expression	2
Antirheumatic Agents	affects cotreatment, decreases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
propionaldehyde	increases expression	1
hydroxyhydroquinone	decreases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
beryllium sulfate	affects binding	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
3-nitrobenzanthrone	decreases expression	1
Bortezomib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Aldehydes	increases expression	1
Amiodarone	increases expression	1
Arsenic	decreases expression	1
Benzalkonium Compounds	affects response to substance	1
Benzene	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Carbamazepine	affects expression	1
Dexamethasone	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	affects methylation	1
Methotrexate	affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_V098	L11.3	Spontaneously immortalized cell line	Male
CVCL_V108	L3.6.2	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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