HLA-DPA1

Summary

HLA-DPA1 (major histocompatibility complex, class II, DP alpha 1, HGNC:4938) is a protein-coding gene on chromosome 6p21.32, encoding HLA class II histocompatibility antigen, DP alpha 1 chain (P20036). 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-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, 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 alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and 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 3113 — RefSeq curated summary.

At a glance

• GWAS associations: 38
• Clinical variants (ClinVar): 56 total
• Phenotypes (HPO): 80
• MANE Select transcript: NM_033554

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4938
Approved symbol	HLA-DPA1
Name	major histocompatibility complex, class II, DP alpha 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000231389
Ensembl biotype	protein_coding
OMIM	142880
Entrez	3113

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000417724, ENST00000419277, ENST00000437811, ENST00000453337, ENST00000463066, ENST00000476642, ENST00000479107, ENST00000692443, ENST00000910957, ENST00000910958, ENST00000923943

RefSeq mRNA: 4 — MANE Select: NM_033554 NM_001242524, NM_001242525, NM_001405020, NM_033554

CCDS: CCDS4764

Canonical transcript exons

ENST00000374808 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 229.8037 / max 12370.6958, expressed in 1216 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73076	224.9018	854
73080	1.2190	552
73064	0.7627	244
73072	0.7479	245
73068	0.5572	203
73071	0.2866	138
73067	0.2481	124
73081	0.2246	138
73079	0.1801	104
73066	0.1589	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.65	gold quality
leukocyte	CL:0000738	99.65	gold quality
granulocyte	CL:0000094	99.60	gold quality
vermiform appendix	UBERON:0001154	99.56	gold quality
lymph node	UBERON:0000029	99.55	gold quality
gall bladder	UBERON:0002110	99.43	gold quality
spleen	UBERON:0002106	99.26	gold quality
right lung	UBERON:0002167	99.22	gold quality
smooth muscle tissue	UBERON:0001135	99.15	gold quality
upper lobe of left lung	UBERON:0008952	99.15	gold quality
duodenum	UBERON:0002114	99.12	gold quality
rectum	UBERON:0001052	98.90	gold quality
right coronary artery	UBERON:0001625	98.67	gold quality
colonic epithelium	UBERON:0000397	98.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.16	gold quality
descending thoracic aorta	UBERON:0002345	97.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.80	gold quality
adipose tissue	UBERON:0001013	97.79	gold quality
tibial nerve	UBERON:0001323	97.75	gold quality
blood	UBERON:0000178	97.71	gold quality
small intestine	UBERON:0002108	97.52	gold quality
thoracic mammary gland	UBERON:0005200	97.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.39	gold quality
omental fat pad	UBERON:0010414	97.32	gold quality
bone marrow	UBERON:0002371	97.29	gold quality
fallopian tube	UBERON:0003889	97.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.06	gold quality
tonsil	UBERON:0002372	96.97	gold quality
lung	UBERON:0002048	96.94	gold quality
left coronary artery	UBERON:0001626	96.92	gold quality

Single-cell (SCXA)

Detected in 42 experiment(s), a significant marker in 32.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	17439.09
E-MTAB-6678	yes	9123.23
E-CURD-126	yes	7329.01
E-MTAB-9801	yes	6493.28
E-MTAB-10287	yes	3518.66
E-GEOD-84465	yes	2770.25
E-GEOD-75688	yes	2759.44
E-MTAB-8322	yes	1341.77
E-MTAB-9906	yes	1213.17
E-MTAB-6701	yes	1210.04
E-ANND-5	yes	756.95
E-MTAB-7407	yes	501.56
E-CURD-98	yes	449.30
E-HCAD-29	yes	262.53
E-HCAD-4	yes	254.85

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

38 targeting HLA-DPA1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421

Literature-anchored findings (GeneRIF, showing 40)

• HLA-DPA1 promoter haplotypes are differently distributed in southern Chinese ethnic groups (PMID:15713216)
• Our findings show that genetic variants in the HLA-DPA1 locus are strongly associated with risk of persistent infection with hepatitis B virus. (PMID:19349983)
• HLA-DPA1 allelic and haplotypic diversity contributes significantly to the risk for type 1 diabetes (PMID:20424227)
• DPA1*020107 was identified from a woman of Ugandan origin by a taxonomy-based sequence analysis of human leukocyte antigen DPA1. It is identical to DPA1*020101 with the exception of a single nucleotide synonymous substitution at codon 58 (GGC–>GGT). (PMID:20470845)
• Genetic variants in the HLA-DP locus are strongly associated with persistent chronic hepatitis B virus infection in the Han Chinese population. (PMID:21274863)
• variants previously associated with chronic hepatitis B are also strongly associated with mRNA expression of HLA-DPA1 and HLA-DPB1, suggesting that expression of these genes is important in control of HBV. (PMID:21346778)
• HLA - DPA1 rs3077 T was strongly associated with decreased risk of chronic hepatitis B virus infection (odds ratio, .62; P = .001), consistent with the previous report. (PMID:21402545)
• genetic variants in the HLA-DPA1 and HLA-DPB1 locus are associated with the risk of pediatric asthma in Asian populations. (PMID:21814517)
• Genetic variants of the HLA-DP genes are risk factors for the development of hepatocellular carcinoma in chinese patients. (PMID:22105689)
• HLA-DPA1 variant is associated with hepatitis B virus infection. (PMID:22448225)
• A novel variant in the HLA-DPB1 3’UTR region, 496A/G, is associated significantly with HBV recovery in European and African-American populations. (PMID:22496224)
• HLA-DP has a role in protection against chronic hepatitis B and viral clearance in Japanese and Koreans (PMID:22737229)
• HLA-DPA1 genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia. (PMID:22923493)
• Data indicate that comparing to GG haplotype of rs3077 (near HLA-DPA1 region) and rs9277535 (near HLA-DPB1 region), GA haplotype had a higher chance of achieving spontaneous HBsAg loss. (PMID:23326374)
• Significant associations of HLA-DP rs3077 and rs9277535 with increased risks of cervical cancer in a Chinese population were found. (PMID:23428460)
• Studied three HLA-DP and IL28B SNPs of CHB patients with and without spontaneous HBsAg seroclearance.Haplotype analysis of HLA-DP polymorphisms showed association with HBsAg seroclearance. (PMID:23449268)
• This is the first study that confirms the association of HLA markers and haplotypes around HLA-DPA1 and HLA-DPB1 with ankylosing spondylitis. (PMID:23459078)
• HLA-DP SNPs rs3077, rs9277378 and rs3128917 were associated with chronicity of HBV disease in the Chinese (PMID:23825586)
• It related to persistence of hepatitis B virus (HBV) infection and viral load in chronic HBV. (PMID:23980639)
• HLA-DP polymorphisms affect affect genotype B hepatitis B virus clearance, regulate immune selection of viral mutations, and influence cirrhosis and hepatocellular carcinoma risks contributed by hepatitis B virus mutations (PMID:24006435)
• HLA-DPA1 and DPB1 allele frequencies and haplotypes of the population of Guadeloupe were most similar to African populations, with characteristic alleles and haplotypes that bespeaks the admixture with other ethnicities. (PMID:24405442)
• Data indicate that CD4+ T cell allorecognition of HLA-DP is significantly affected by DPA1 polymorphism. (PMID:24462895)
• Single nucleotide polymorphisms rs3077 and rs9277378 in HLA-DPA1 and HLA-DPB1 are significantly associated with protective effects against chronic hepatitis B. (PMID:24465836)
• This resource provides population estimates of the frequencies of HLA alleles at these eight loci in the three population groups, particularly for HLA-DPA1 and HLA-DPB1 that were not assayed in HapMap. (PMID:24698974)
• rs3077 in HLA-DPA1 is a significantly associated SNP associated with chronic hepatitis B virus infection and viral clearance. (PMID:24846544)
• The study suggests that HLA-DPA1/B1 loci are candidate susceptibility regions that have some marker single nucleotide polymorphisms for both chronic hepatitis C virus infection and F protein generation in the Han Chinese population. (PMID:24897020)
• Crystal structure of the extracellular region of the HLA-DPA1/DPB1 heterodimer, in complex with the major antigenic peptide from the Japanese cedar pollen allergen. (PMID:25020231)
• HLA-DP gene polymorphisms are strongly associated with chronic hepatitis B virus infection. (PMID:25449085)
• DPA1*02:01- DPB1*14:01 and DPA1*02:01- DPB1*17:01 haplotypes provide considerable protection effect against Posner-Schlossman syndrome. (PMID:25863099)
• Single-nucleotide polymorphism in HLA-DP is associated with cervical cancer susceptibility. (PMID:26711785)
• HLA-DPA1 and HLA-DPB1 variants can determine susceptibility or protective effect against Hepatitis B virus infection in an Indonesian population. (PMID:27051043)
• Single-nucleotide polymorphism in HLA-DPA1 gene is associated with sclerotic graft-versus-host disease. (PMID:27313329)
• The HLA-B*42, HLA-C*17, HLA-DPA1*03, and HLA-DPB1*105 genotypes were associated with allergic asthma and the HLA-B*48 genotype with the nonallergic phenotype. The presence of the haplotype HLA-DPA1*03 DQA*05 was associated with allergic asthma, and the presence of HLA-DPA1*03 and the absence of HLA-DQA*05 with nonallergic asthma. (PMID:28380482)
• These results suggest the involvement of class II molecules HLA-DPA1 and HLA-DPB1 in hepatitis B virus reactivation after treatment with immunomodulatory agents. (PMID:29283185)
• expression of HLA-DPA1 alleles and rs3077 affected the risk of chronic hepatitis B virus infection (PMID:30267609)
• Study examined the role of the binding pockets of HLA-DPA1, -DQA1 and-DRB1 in the severe form of West Nile Virus disease. Protein modeling of these molecules revealed structural and functional differences among alleles with opposite roles concerning the development of the disease. (PMID:30379846)
• A significant difference in the allele distributions was observed only for the rs3077 SNP between the healthy controls and the chronic HBV infections (CHB) group as well as between the spontaneous HBsAg seroclearance and CHB groups. This is the first study demonstrating an association of the HLA-DPA1 rs3077-T allele with spontaneous HBsAg seroclearance in Caucasians. (PMID:30471179)
• Polymorphic variation at the HLA-DPA1/DPB1 locus is strongly associated with both the age at diagnosis and prognosis in Pulmonary Arterial Hypertension. (PMID:30527956)
• HLA-DPA1 gene polymorphism in primary glaucoma. (PMID:31389567)
• Coordinated DNA Methylation and Gene Expression Data for Identification of the Critical Genes Associated with Childhood Atopic Asthma. (PMID:31460781)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	RT1-Ha	ENSRNOG00000045908

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-DPB1 (ENSG00000223865), HLA-DQB2 (ENSG00000232629), HLA-DQA2 (ENSG00000237541), HLA-DOB (ENSG00000241106), HLA-DMB (ENSG00000242574)

Protein

Protein identifiers

HLA class II histocompatibility antigen, DP alpha 1 chain — P20036 (reviewed: P20036)

Alternative names: DP(W3), DP(W4), HLA-SB alpha chain, MHC class II DP3-alpha, MHC class II DPA1

All UniProt accessions (5): P20036, F6V115, H0Y6F8, J3KQ99, X5CKE2

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 DPA1 are known: DPA101:03, DPA101:04, DPA101:05, DPA101:06, DPA101:07, DPA101:08, DPA101:09, DPA101:10, DPA102:01, DPA102:02, DPA102:03, DPA102:04, DPA103:01, DPA103:02, DPA103:03, DPA104:01 The sequence shown is that of DPA1*01:03.

Similarity. Belongs to the MHC class II family.

RefSeq proteins (4): NP_001229453, NP_001229454, NP_001391949, NP_291032* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001003	MHC_II_a_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: PF00993, PF07654

UniProt features (52 total): sequence variant 23, strand 13, region of interest 3, glycosylation site 2, topological domain 2, helix 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1, sequence conflict 1, turn 1, domain 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-P20036-F1	90.36	0.77

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 (1): 138–194

Glycosylation sites (2): 149, 109

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: 484 (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, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOCC_VACUOLAR_MEMBRANE, GOZGIT_ESR1_TARGETS_DN, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GAURNIER_PSMD4_TARGETS

GO Biological Process (12): adaptive immune response (GO:0002250), peptide antigen assembly with MHC class II protein complex (GO:0002503), immune response (GO:0006955), 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), positive regulation of T cell activation (GO:0050870), cellular response to type II interferon (GO:0071346), 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 (4): MHC class II protein complex binding (GO:0023026), MHC class II receptor activity (GO:0032395), 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), 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), membrane (GO:0016020)

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
response to stimulus	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
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1
response to type II interferon	1
cellular response to cytokine stimulus	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
binding	1
Golgi apparatus	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

30 interactions, top by confidence:

A	B	Type	Score
HLA-DPA1	SREBF2	psi-mi:“MI:0915”(physical association)	0.670
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
ERBB3	SLC31A1	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
GAL	HLA-DPA1	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	CD74	psi-mi:“MI:0915”(physical association)	0.400
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PLXNC1	POTEF	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
ADPGK	TOR1B	psi-mi:“MI:0914”(association)	0.350
CD1A	EXTL3	psi-mi:“MI:0914”(association)	0.350
LAG3	PCDH7	psi-mi:“MI:0914”(association)	0.350
GALNT10	PLXNA2	psi-mi:“MI:0914”(association)	0.350
FSTL1	HLA-DPB1	psi-mi:“MI:0914”(association)	0.350
CHST12	HSPA5	psi-mi:“MI:0914”(association)	0.350
BPIFA1	HLA-DPA1	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	HLA-DQB1	psi-mi:“MI:0914”(association)	0.350
ADPGK	HLA-DPA1	psi-mi:“MI:0914”(association)	0.350
SLC12A5	KIF2A	psi-mi:“MI:0914”(association)	0.350
SLC38A10	XPOT	psi-mi:“MI:0914”(association)	0.350
SLC3A1	ILVBL	psi-mi:“MI:0914”(association)	0.350
prfC	HLA-DPA1	psi-mi:“MI:0915”(physical association)	0.000
HLA-DPA1		psi-mi:“MI:0915”(physical association)	0.000
HLA-DPA1	iucD	psi-mi:“MI:0915”(physical association)	0.000
	HLA-DPA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (240): MYO9B (Affinity Capture-MS), DIMT1 (Affinity Capture-MS), ASPM (Affinity Capture-MS), RMDN3 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS), HLA-F (Affinity Capture-MS), HLA-A (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), TOR1B (Affinity Capture-MS), KIDINS220 (Affinity Capture-MS), ATP13A2 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), C17orf80 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS)

ESM2 similar proteins: A0A5B9, P01850, P01851, P01852, P01862, P01863, P01864, P01865, P01867, P01868, P01869, P01870, P01871, P01895, P01896, P01903, P01906, P01909, P01910, P03987, P04221, P04228, P06333, P0DSE2, P0DTU4, P11364, P14434, P15980, P15981, P20036, P20037, P20759, P20760, P20761, P20762, P23150, P30378, P35613, P57087, P59822

Diamond homologs: O42197, O77517, O77518, O77519, O77520, O77521, O77523, O77524, O77525, O77526, O77528, O77529, O77530, O77531, O77532, O77533, O77534, O77535, O77536, O77537, P01844, P01885, P01886, P01887, P01888, P01906, P01910, P04227, P04228, P04440, P07151, P14434, P14435, P14436, P14437, P14438, P15981, P16213, P19341, P20036

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“RFX complex”	“up-regulates quantity by expression”	HLA-DPA1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1267 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33069017:ACC:A	donor_gain	1.0000
6:33069018:CCC:C	donor_gain	1.0000
6:33069300:TCTG:T	acceptor_loss	1.0000
6:33069301:C:CC	acceptor_gain	1.0000
6:33069301:C:T	acceptor_loss	1.0000
6:33069302:T:G	acceptor_loss	1.0000
6:33069635:GCGTA:G	donor_loss	1.0000
6:33069636:CGTAC:C	donor_loss	1.0000
6:33069637:GTAC:G	donor_loss	1.0000
6:33069638:TACC:T	donor_loss	1.0000
6:33069639:A:AC	donor_gain	1.0000
6:33069639:A:T	donor_loss	1.0000
6:33069640:C:CC	donor_gain	1.0000
6:33069640:C:CG	donor_loss	1.0000
6:33069883:TCCG:T	acceptor_gain	1.0000
6:33069884:CCG:C	acceptor_gain	1.0000
6:33069884:CCGC:C	acceptor_gain	1.0000
6:33069885:CG:C	acceptor_gain	1.0000
6:33069885:CGC:C	acceptor_gain	1.0000
6:33069887:C:CC	acceptor_gain	1.0000
6:33069890:C:CT	acceptor_gain	1.0000
6:33069891:A:AC	acceptor_gain	1.0000
6:33069891:A:C	acceptor_gain	1.0000
6:33069898:CAG:C	acceptor_gain	1.0000
6:33069899:A:T	acceptor_gain	1.0000
6:33069900:G:C	acceptor_gain	1.0000
6:33069900:G:GC	acceptor_gain	1.0000
6:33076138:CCAGG:C	donor_loss	1.0000
6:33076139:CAGGT:C	donor_loss	1.0000
6:33076140:AGGT:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000127410 (6:33078551 A>C), RS1000357828 (6:33076538 C>T), RS1000615064 (6:33065006 C>T), RS1000958471 (6:33075239 C>T), RS1001067267 (6:33070046 G>A), RS1001154141 (6:33068570 A>G), RS1001307177 (6:33074991 T>G), RS1001455743 (6:33073071 G>C,T), RS1001630799 (6:33077606 G>A,C), RS1001681768 (6:33072306 A>G), RS1001726438 (6:33069405 C>A), RS1001780053 (6:33065269 G>T), RS1001907437 (6:33066384 A>G), RS1002327053 (6:33082602 G>A), RS1002417445 (6:33081712 T>G)

Disease associations

OMIM: gene MIM:142880 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

80 total (30 of 80 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

38 associations (top):

Study	Trait	p-value
GCST001009_1	Nephropathy	5.000000e-09
GCST001150_2	Hepatitis B	2.000000e-61
GCST001156_12	Systemic sclerosis	2.000000e-20
GCST001582_1	Hepatitis B (viral clearance)	1.000000e-09
GCST001582_3	Hepatitis B (viral clearance)	4.000000e-45
GCST002217_5	Sjögren’s syndrome	9.000000e-25
GCST002655_14	IgA nephropathy	5.000000e-07
GCST002655_17	IgA nephropathy	5.000000e-07
GCST002655_23	IgA nephropathy	2.000000e-11
GCST002879_9	Chronic hepatitis B infection	1.000000e-53
GCST003092_10	Myositis	2.000000e-12
GCST003092_9	Myositis	9.000000e-13
GCST003817_8	Mortality in sepsis	2.000000e-06
GCST003976_5	Antineutrophil cytoplasmic antibody-associated vasculitis	6.000000e-71
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
GCST004748_118	Lung cancer	1.000000e-06
GCST004749_12	Lung cancer in ever smokers	4.000000e-06
GCST005038_66	Allergic disease (asthma, hay fever or eczema)	8.000000e-12
GCST005606_19	Response to hepatitis B vaccine	1.000000e-07
GCST006575_42	Takayasu arteritis	4.000000e-06
GCST007228_1	Pulmonary arterial hypertension	8.000000e-20
GCST007798_47	Asthma	4.000000e-06
GCST007800_13	Asthma (childhood onset)	2.000000e-13
GCST008870_40	Keratinocyte cancer (MTAG)	2.000000e-09
GCST008916_109	Asthma	7.000000e-11
GCST008916_90	Asthma	4.000000e-15
GCST010796_1576	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010985_37	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	4.000000e-11

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0004645	response to vaccine
EFO:0010176	keratinocyte carcinoma
EFO:0004327	electrocardiography
EFO:0004847	age at onset
EFO:0004918	age at diagnosis
EFO:0008405	susceptibility to hepatitis B infection measurement
EFO:0004842	eosinophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
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

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3077	Efficacy	3	peginterferon alfa-2b	Hepatitis B;Chronic

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3077	HLA-DPA1	3	2.50	1	peginterferon alfa-2b
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

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	3
Valproic Acid	affects expression, increases expression	3
Vorinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Ozone	affects expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
tungsten carbide	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	increases expression	1
hydroxyhydroquinone	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
tetrathiomolybdate	increases expression	1
pentanal	increases expression	1
tamibarotene	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
valdecoxib	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	increases expression	1

Clinical trials (associated diseases)

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