HLA-DQB1

Summary

HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1, HGNC:4944) is a protein-coding gene on chromosome 6p21.32, encoding HLA class II histocompatibility antigen, DQ beta 1 chain (P01920). 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-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), 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 it contains six exons. Exon 1 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 DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3119 — RefSeq curated summary.

At a glance

• GWAS associations: 270
• Clinical variants (ClinVar): 54 total — 1 likely-pathogenic
• Phenotypes (HPO): 127
• MANE Select transcript: NM_002123

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4944
Approved symbol	HLA-DQB1
Name	major histocompatibility complex, class II, DQ beta 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	IDDM1, CELIAC1
Ensembl gene	ENSG00000179344
Ensembl biotype	protein_coding
OMIM	604305
Entrez	3119

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000374943, ENST00000399079, ENST00000399082, ENST00000399084, ENST00000434651, ENST00000443574, ENST00000460185, ENST00000484729, ENST00000487676, ENST00000922190, ENST00000955676, ENST00000955677

RefSeq mRNA: 2 — MANE Select: NM_002123 NM_001243961, NM_002123

CCDS: CCDS43451, CCDS59006

Canonical transcript exons

ENST00000434651 — 5 exons

Exon	Start	End
ENSE00001596914	32661967	32662248
ENSE00001817837	32666499	32666657
ENSE00003421994	32664798	32665067
ENSE00003507676	32659467	32660249
ENSE00003562109	32661347	32661457

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.09.

FANTOM5 (CAGE): breadth broad, TPM avg 67.4843 / max 4913.5965, expressed in 881 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72999	66.5244	873
72995	0.2598	135
72996	0.1991	111
73002	0.1359	52
72993	0.1017	45
72992	0.0738	35
72997	0.0664	34
73001	0.0648	27
73000	0.0585	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.09	gold quality
spleen	UBERON:0002106	99.04	gold quality
upper lobe of left lung	UBERON:0008952	98.96	gold quality
gall bladder	UBERON:0002110	98.88	gold quality
lymph node	UBERON:0000029	98.74	gold quality
monocyte	CL:0000576	98.53	gold quality
granulocyte	CL:0000094	98.52	gold quality
upper lobe of lung	UBERON:0008948	98.39	gold quality
leukocyte	CL:0000738	98.02	gold quality
mononuclear cell	CL:0000842	97.94	gold quality
right coronary artery	UBERON:0001625	97.69	gold quality
rectum	UBERON:0001052	97.37	gold quality
visceral pleura	UBERON:0002401	97.33	gold quality
vermiform appendix	UBERON:0001154	97.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.26	gold quality
skin of hip	UBERON:0001554	97.06	gold quality
ileal mucosa	UBERON:0000331	96.72	gold quality
tibial nerve	UBERON:0001323	96.55	gold quality
pleura	UBERON:0000977	96.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.18	gold quality
skin of abdomen	UBERON:0001416	96.15	gold quality
skin of leg	UBERON:0001511	96.13	gold quality
parietal pleura	UBERON:0002400	95.80	gold quality
caecum	UBERON:0001153	95.78	gold quality
thymus	UBERON:0002370	95.76	gold quality
metanephros cortex	UBERON:0010533	95.56	gold quality
apex of heart	UBERON:0002098	95.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.19	gold quality
omental fat pad	UBERON:0010414	95.07	gold quality
peritoneum	UBERON:0002358	95.06	gold quality

Single-cell (SCXA)

Detected in 41 experiment(s), a significant marker in 39.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	3824.77
E-MTAB-8142	yes	3777.01
E-HCAD-36	yes	3594.34
E-MTAB-8322	yes	3506.45
E-GEOD-135922	yes	3150.36
E-MTAB-9906	yes	2629.49
E-GEOD-130148	yes	2538.13
E-GEOD-139324	yes	2512.87
E-MTAB-8495	yes	2428.60
E-MTAB-6653	yes	1979.01
E-CURD-55	yes	1917.21
E-CURD-79	yes	1889.08
E-GEOD-84465	yes	1723.74
E-MTAB-9467	yes	1547.38
E-HCAD-24	yes	1494.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CIITA, CREB1, DEK, ESR1, ESR2, IRF6, PAX3, RFX5, RFXANK, RFXAP, SP1, SPI1, TBX5, THRA, TP63, VSX2, YBX1

miRNA regulators (miRDB)

39 targeting HLA-DQB1, 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-6798-5P	100.00	65.77	699
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-1285-3P	97.72	67.02	1932

Literature-anchored findings (GeneRIF, showing 18)

• association of TNF alleles with HLA-DR, -DQ and -B alleles in 216 healthy individuals from the north of England (PMID:11841486)
• A retroviral long terminal repeat adjacent to the gene modifies type I diabetes susceptibility on high risk DQ haplotypes. (PMID:11914751)
• Relative and absolute HLA-DQA1-DQB1 linked risk for developing type I diabetes before 40 years of age in the Belgian population (PMID:11916169)
• Relationship between HLA-DQA1, -DQB1 genes polymorphism and susceptilibity to bronchial asthma among Northern Hans (PMID:11953202)
• Lack of evidence for association of HLA-DQB1 genes and gastric cancer carcinogenesis or H. pylori infection. (PMID:11972882)
• HLA-DQB1 alleles are associated with susceptibility or resistance to gastric cancer and also influence its clinical features (PMID:11985790)
• HLA-DRB1, DQB1, and DQA1 allele profile in Brazilian patients with type 1 diabetes mellitus. (PMID:12021129)
• Molecular modeling of eluted peptides from DQ6 molecules (DQB1*0602 and DQB1*0604) negatively and positively associated with type 1 diabetes (PMID:12021132)
• The combination of several polymorphic amino acid residues in the DQalpha and DQbeta chains forms a domain structure pattern and is associated with insulin-dependent diabetes mellitus. (PMID:12021143)
• genotype influences the relative risk of type 1 diabetes conferred by dietary factors (PMID:12027934)
• Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus (PMID:12028537)
• HLA DQA1-DQB1 genotypes in Bedouin families with celiac disease. (PMID:12039527)
• The 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.(DQB1) (PMID:12070003)
• Women carrying the HLA-DQB1*0301 allele have an increased risk of developing CIN when infected by HPV 16, although there was not an increased frequency of recurrent disease among women carrying this allele. (PMID:12090587)
• HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human systemic lupus erythematosus (PMID:12145745)
• Six different variants, including a novel polymorphic site, were detected in exon 1. (PMID:12358858)
• DQB1*0604 was found to be strongly associated with non-obstructive azoospermia and haplotype analysis suggested that the DQB1*0604 allele may play a decisive role in the pathogenesis of non-obstructive azoospermia. (PMID:12366783)
• the major histocompatibility complex region’s conferred susceptibility to CD is very similar to that observed for DM1, with shared risk and protective haplotypes. (PMID:12366785)

Cross-species orthologs

0 orthologs

Paralogs (13): B2M (ENSG00000166710), HLA-DRB1 (ENSG00000196126), 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, DQ beta 1 chain — P01920 (reviewed: P01920)

Alternative names: MHC class II antigen DQB1

All UniProt accessions (5): A2AAY8, A2AAZ0, E9PIB1, Q5SU54, Q5Y7D6

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-DQB1 are known: DQB102:01, DQB102:02, DQB102:03, DQB102:04, DQB102:05, DQB103:01, DQB103:02, DQB103:03, DQB103:04, DQB103:05, DQB103:06, DQB103:07, DQB103:08, DQB103:09, DQB103:10, DQB103:11, DQB103:12, DQB103:13, DQB103:14, DQB103:15, DQB103:16, DQB103:17, DQB103:18, DQB103:19, DQB103:20, DQB103:21, DQB103:22, DQB103:23, DQB103:24, DQB103:25, DQB103:26, DQB104:01, DQB104:02, DQB104:03, DQB105:01, DQB105:02, DQB105:03, DQB105:04, DQB105:05, DQB106:01, DQB106:02, DQB106:03, DQB106:04, DQB106:05, DQB106:06, DQB106:07, DQB106:08, DQB106:09, DQB106:10, DQB106:11, DQB106:12, DQB106:13, DQB106:14, DQB106:15, DQB106:16, DQB106:17, DQB106:18, DQB106:19, DQB106:20, DQB106:21, DQB106:22, DQB106:23, DQB106:24, DQB106:25, DQB106:27, DQB106:28, DQB106:29, DQB106:30, DQB106:31, DQB106:32, DQB106:33, DQB106:34, DQB106:35, DQB106:36, DQB106:37, DQB106:38, and DQB106:39. The sequence shown is that of DQB103:01. DQ2 (heterodimer of DQA105:01/DQB102:01) is associated with more than 90% of celiac disease patients. A minority displays DQ8 (heterodimer of DQA103/DQB103:02). DQ0602 (heterodimer of DQA101:02/DQB106:02) confers dominant protection against type 1 diabetes (T1D) and strong susceptibility to narcolepsy. DQB106:02 has been found to be present in most of the narcolepsy patients. As well 98% of the patients with an HCRT deficiency are positive for DQB106:02.

Similarity. Belongs to the MHC class II family.

RefSeq proteins (2): NP_001230890, NP_002114* (*=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 (124 total): sequence variant 86, strand 14, helix 6, sequence conflict 4, region of interest 3, disulfide bond 2, turn 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
1UVQ	X-RAY DIFFRACTION	1.8
2NNA	X-RAY DIFFRACTION	2.1
1S9V	X-RAY DIFFRACTION	2.22
1JK8	X-RAY DIFFRACTION	2.4
4OZF	X-RAY DIFFRACTION	2.7
4OZH	X-RAY DIFFRACTION	2.8
4OZG	X-RAY DIFFRACTION	3
8VSP	ELECTRON MICROSCOPY	3.12
4GG6	X-RAY DIFFRACTION	3.2
4OZI	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01920-F1	87.36	0.70

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): 47–111, 149–205

Glycosylation sites (1): 51

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: 553 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, 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, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOCC_VACUOLAR_MEMBRANE, MODULE_45, MODULE_418, GOZGIT_ESR1_TARGETS_DN, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, HSIAO_HOUSEKEEPING_GENES, GAURNIER_PSMD4_TARGETS, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN

GO Biological Process (11): adaptive immune response (GO:0002250), peptide antigen assembly with MHC class II protein complex (GO:0002503), immune response (GO:0006955), humoral immune response (GO:0006959), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), 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), antigen processing and presentation (GO:0019882)

GO Molecular Function (3): MHC class II protein complex binding (GO:0023026), MHC class II receptor activity (GO:0032395), peptide antigen binding (GO:0042605)

GO Cellular Component (15): Golgi membrane (GO:0000139), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), 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), 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
immune response	3
cytoplasmic vesicle membrane	3
antigen processing and presentation of peptide antigen via MHC class II	2
immune system process	2
MHC class II protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
response to stimulus	1
antigen processing and presentation of exogenous peptide antigen	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
MHC protein complex binding	1
transmembrane signaling receptor activity	1
MHC class II protein binding	1
immune receptor activity	1
antigen binding	1
peptide binding	1
Golgi apparatus	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1
cellular anatomical structure	1
transport vesicle	1
endocytic vesicle	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1
late endosome	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

43 interactions, top by confidence:

A	B	Type	Score
HLA-DQA1	HLA-DQB1	psi-mi:“MI:0915”(physical association)	0.860
HLA-DQB1	HLA-DQA1	psi-mi:“MI:0915”(physical association)	0.860
HLA-DQA1	HLA-DQB1	psi-mi:“MI:2364”(proximity)	0.860
HLA-DQA1	HLA-DQB1	psi-mi:“MI:0407”(direct interaction)	0.860
HLA-DQA1	HCRT	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
HLA-DQB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ESYT2	psi-mi:“MI:0914”(association)	0.350
APOM	ESYT2	psi-mi:“MI:0914”(association)	0.350
HLA-DQB1	PIPSL	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASIC4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TMEM87A	POTEF	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
IDS	RTCA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): HLA-DQB1 (FRET), HLA-DQA1 (Affinity Capture-Luminescence), HLA-DQA1 (FRET), HLA-DQB1 (Affinity Capture-Luminescence), HLA-DQB1 (Affinity Capture-RNA), CPT1A (Affinity Capture-MS), TAPBP (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), NDUFA12 (Affinity Capture-MS), KCNJ8 (Affinity Capture-MS), SEMA4F (Affinity Capture-MS), HLA-DQB1 (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: 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

3 interactions.

A	Effect	B	Mechanism
CIITA	“up-regulates quantity by expression”	HLA-DQB1	“transcriptional regulation”
MARCHF9	“down-regulates quantity by destabilization”	HLA-DQB1	ubiquitination
“RFX complex”	“up-regulates quantity by expression”	HLA-DQB1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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	5	21.6×	4e-04
Neutrophil degranulation	7	5.6×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
adaptive immune response	7	13.7×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	0
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3256932	NM_002123.5(HLA-DQB1):c.370_379+2del	Likely pathogenic

SpliceAI

798 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32661954:AATAT:A	donor_gain	1.0000
6:32661965:A:AC	donor_gain	1.0000
6:32661966:C:CC	donor_gain	1.0000
6:32661966:CG:C	donor_gain	1.0000
6:32661966:CGCCA:C	donor_gain	1.0000
6:32662244:CTCCA:C	acceptor_gain	1.0000
6:32662245:TCCA:T	acceptor_gain	1.0000
6:32662246:CCA:C	acceptor_gain	1.0000
6:32662246:CCAC:C	acceptor_gain	1.0000
6:32662247:CA:C	acceptor_gain	1.0000
6:32662247:CAC:C	acceptor_gain	1.0000
6:32662249:C:CC	acceptor_gain	1.0000
6:32664792:GCTCA:G	donor_loss	1.0000
6:32664794:TCA:T	donor_loss	1.0000
6:32664795:CA:C	donor_loss	1.0000
6:32664797:CC:C	donor_loss	1.0000
6:32664797:CCT:C	donor_gain	1.0000
6:32664884:T:TA	donor_gain	1.0000
6:32666493:ACTT:A	donor_loss	1.0000
6:32666494:CTTA:C	donor_loss	1.0000
6:32666495:TTAC:T	donor_loss	1.0000
6:32666496:TACCG:T	donor_loss	1.0000
6:32666497:A:AC	donor_gain	1.0000
6:32666497:AC:A	donor_gain	1.0000
6:32666497:ACCG:A	donor_loss	1.0000
6:32666498:C:CC	donor_gain	1.0000
6:32666498:CC:C	donor_gain	1.0000
6:32666498:CCGGG:C	donor_gain	1.0000
6:32661957:ATCC:A	donor_gain	0.9900
6:32661965:ACG:A	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002502794 (6:32667892 C>A), RS1003909765 (6:32668490 C>T), RS1005242971 (6:32660528 C>T), RS1005950617 (6:32667824 A>G), RS1006054691 (6:32663320 G>A,T), RS1007166295 (6:32668493 C>G), RS1009865999 (6:32660439 C>A,T), RS1009881785 (6:32668289 A>T), RS1010519849 (6:32668132 A>T), RS1012632539 (6:32659287 C>T), RS1014192461 (6:32661821 G>A), RS1014513276 (6:32660109 G>A,C,T), RS1015577654 (6:32666820 G>A), RS1018931632 (6:32668501 A>G), RS1019543462 (6:32660968 G>A,C,T)

Disease associations

OMIM: gene MIM:604305 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

127 total (30 of 127 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000017	Nocturia
HP:0000019	Urinary hesitancy
HP:0000020	Urinary incontinence
HP:0000505	Visual impairment
HP:0000605	Supranuclear gaze palsy
HP:0000651	Diplopia
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000711	Restlessness
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000726	Dementia
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000746	Delusion
HP:0000751	Personality changes
HP:0000789	Infertility
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000826	Precocious puberty
HP:0000939	Osteoporosis
HP:0000964	Eczematoid dermatitis
HP:0000975	Hyperhidrosis
HP:0000989	Pruritus
HP:0001025	Urticaria

GWAS associations

270 associations (top):

Study	Trait	p-value
GCST000311_1	Ulcerative colitis	1.000000e-16
GCST000408_6	Primary biliary cholangitis	1.000000e-10
GCST000408_7	Primary biliary cholangitis	7.000000e-10
GCST000612_35	Celiac disease	1.000000e-50
GCST000629_1	Knee osteoarthritis	5.000000e-09
GCST000650_2	Systemic sclerosis	4.000000e-17
GCST000680_2	Multiple sclerosis	1.000000e-20
GCST000733_6	Primary biliary cholangitis	3.000000e-26
GCST000734_2	Follicular lymphoma	1.000000e-29
GCST001009_5	Nephropathy	2.000000e-26
GCST001051_1	Follicular lymphoma	2.000000e-21
GCST001150_1	Hepatitis B	4.000000e-37
GCST001156_11	Systemic sclerosis	1.000000e-07
GCST001156_7	Systemic sclerosis	3.000000e-54
GCST001183_12	Asthma	5.000000e-15
GCST001225_1	HPV seropositivity	1.000000e-14
GCST001248_18	Pulmonary function	6.000000e-06
GCST001323_1	Nodular sclerosis Hodgkin lymphoma	8.000000e-18
GCST001323_2	Nodular sclerosis Hodgkin lymphoma	2.000000e-07
GCST001474_7	Hypothyroidism	5.000000e-07
GCST001679_3	Complement C3 and C4 levels	3.000000e-22
GCST001679_4	Complement C3 and C4 levels	9.000000e-83
GCST001728_3	Ulcerative colitis	5.000000e-133
GCST001739_1	IgE levels	2.000000e-07
GCST001784_25	Pulmonary function (smoking interaction)	4.000000e-09
GCST001784_43	Pulmonary function (smoking interaction)	4.000000e-09
GCST001785_9	Crohn’s disease	9.000000e-59
GCST001812_2	Epstein-Barr virus immune response (EBNA-1)	2.000000e-10
GCST001826_4	Lymphoma	4.000000e-10
GCST001826_7	Lymphoma	2.000000e-06

EFO canonical traits (60, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004510	HPV seropositivity
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004984	complement C4 measurement
EFO:0005206	oligoclonal band measurement
EFO:0005298	allergic sensitization measurement
EFO:0007017	peanut allergy measurement
EFO:0007626	emphysema imaging measurement
EFO:0004458	C-reactive protein measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007949	acute-on-chronic liver failure
EFO:0004314	forced expiratory volume
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:1000965	Henoch-Schoenlein purpura
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008401	susceptibility to shingles measurement
EFO:0008405	susceptibility to hepatitis B infection 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:0004645	response to vaccine
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

9 annotations.

Variant	Type	Level	Drugs	Phenotypes
HLA-DQB1*02:01	Toxicity	3	infliximab	Drug-induced liver injury
HLA-DQB1*02:02	Toxicity	3	pegaspargase
HLA-DQB1*02:02	Toxicity	3	acetaminophen	Severe Cutaneous Adverse Reactions
HLA-DQB1*05:01	Toxicity	3	nevirapine	Drug Hypersensitivity
HLA-DQB1*05:02	Toxicity	3	allopurinol	Severe Cutaneous Adverse Reactions;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
HLA-DQB1*05:02	Toxicity	3	flupirtine	Drug-induced liver injury
HLA-DQB1*06:01	Toxicity	3	Antithyroid Preparations	Agranulocytosis;Graves Disease
HLA-DQB1*06:02	Toxicity	3	Influenza vaccines	Narcolepsy
rs9274407	Toxicity	3	amoxicillin;clavulanate	Drug Toxicity

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9274407	HLA-DQB1	3	0.00	1	amoxicillin;clavulanate
rs113332494	HLA-DQB1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Doxorubicin	decreases expression, decreases response to substance	3
Arsenic	affects expression, decreases response to substance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Mercury	decreases expression, increases expression	2
Nickel	increases expression	2
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
pyrimidin-2-one beta-ribofuranoside	increases expression	1
testosterone undecanoate	increases expression, affects cotreatment	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
nickel chloride	affects cotreatment, increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
lumiracoxib	affects response to substance	1
clothianidin	increases expression	1
beta-hydroxy simvastatin acid	decreases expression	1
ON 01910	affects expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Oxaprozin	affects expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

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