HLA-DRB5

Summary

HLA-DRB5 (major histocompatibility complex, class II, DR beta 5, HGNC:4953) is a protein-coding gene on chromosome 6p21.32, encoding HLA class II histocompatibility antigen, DR beta 5 chain (Q30154). 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-DRB5 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) 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. 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 DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene.

Source: NCBI Gene 3127 — RefSeq curated summary.

At a glance

• GWAS associations: 108
• Clinical variants (ClinVar): 74 total
• Druggable target: yes
• MANE Select transcript: NM_002125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4953
Approved symbol	HLA-DRB5
Name	major histocompatibility complex, class II, DR beta 5
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198502
Ensembl biotype	protein_coding
OMIM	604776
Entrez	3127

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000374975, ENST00000714490, ENST00000871536, ENST00000871537, ENST00000943826, ENST00000943827

RefSeq mRNA: 1 — MANE Select: NM_002125 NM_002125

CCDS: CCDS4751

Canonical transcript exons

ENST00000374975 — 6 exons

Exon	Start	End
ENSE00001641881	32519370	32519651
ENSE00001715371	32518556	32518666
ENSE00001768120	32521905	32522174
ENSE00001776788	32518054	32518077
ENSE00001833430	32517353	32517752
ENSE00001920389	32530125	32530287

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 99.33.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2769 / max 38.8763, expressed in 120 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72963	7.4389	481
72962	0.3835	151
72976	0.2769	120
72964	0.2455	76
203957	0.2234	127
72961	0.0039	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.33	gold quality
lymph node	UBERON:0000029	98.80	gold quality
vermiform appendix	UBERON:0001154	98.50	gold quality
duodenum	UBERON:0002114	98.31	gold quality
leukocyte	CL:0000738	98.30	gold quality
monocyte	CL:0000576	98.28	gold quality
upper lobe of left lung	UBERON:0008952	97.25	gold quality
right coronary artery	UBERON:0001625	96.93	gold quality
spleen	UBERON:0002106	96.46	gold quality
right lung	UBERON:0002167	96.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.85	gold quality
right uterine tube	UBERON:0001302	95.07	gold quality
blood	UBERON:0000178	94.67	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.65	gold quality
adipose tissue	UBERON:0001013	94.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.91	gold quality
left coronary artery	UBERON:0001626	93.37	gold quality
omental fat pad	UBERON:0010414	93.34	gold quality
small intestine	UBERON:0002108	93.24	gold quality
tibial nerve	UBERON:0001323	93.19	gold quality
fallopian tube	UBERON:0003889	92.99	gold quality
descending thoracic aorta	UBERON:0002345	92.47	gold quality
thoracic mammary gland	UBERON:0005200	92.28	gold quality
adult mammalian kidney	UBERON:0000082	92.25	gold quality
lung	UBERON:0002048	92.17	gold quality
left adrenal gland cortex	UBERON:0035825	92.10	gold quality
rectum	UBERON:0001052	91.03	gold quality
thoracic aorta	UBERON:0001515	90.94	gold quality
left uterine tube	UBERON:0001303	90.78	gold quality
right adrenal gland	UBERON:0001233	90.64	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	7938.30
E-HCAD-36	yes	5407.12
E-HCAD-15	yes	4514.22
E-MTAB-8322	yes	4322.03
E-GEOD-84465	yes	3643.13
E-CURD-55	yes	3253.16
E-MTAB-9906	yes	3106.83
E-MTAB-6308	yes	2721.62
E-CURD-126	yes	2278.98
E-CURD-85	yes	1721.26
E-GEOD-149689	yes	1712.16
E-GEOD-130148	yes	1617.70
E-MTAB-9435	yes	1501.97
E-MTAB-6678	yes	1412.22
E-GEOD-76312	yes	1370.04

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

21 targeting HLA-DRB5, 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-4731-5P	99.89	67.23	2537
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-8071	95.69	64.93	484

Literature-anchored findings (GeneRIF, showing 24)

• the identification of a new HLA-DRB5 allele found in two members of a British Caucasoid family. (PMID:14617041)
• hMBP82-100-specific type B T cells escaped tolerance in HLA-DRB5*0101 Tg mice (PMID:18713991)
• roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis (PMID:18832704)
• the gene frequency of HLADR5 was significantly decreased in the total group of patients with autoimmune liver disease (PMID:19811438)
• In our study, we found that the HLA-DR9 allele and HPV16E6 infection had a function of synergy in the process of malignant transformation of esophageal epithelial cells, and jointly promoting the occurrence and development of esophageal cancer. (PMID:20193235)
• DNA methylation of CpG dinucleotides across HLA-DRB1*1501 and HLA-DRB5 does not determine whether patients manifest benign or malignant multiple sclerosis. (PMID:20394989)
• HLA-DRB5 was found to have bimodal expression in human skeletal muscle tissue. (PMID:21299892)
• Eighteen out of 19 individuals showed HLA-DRB5, and none of the HLA-DRB5*null individuals, carried the HLADRB1* 15 allele. The findings support a contribution for HLA-DRB5 in keloid pathogenesis. (PMID:22033527)
• There are no significant differences in the HLA-DRB3/B4/B5 homozygosity and heterozygosity rates between Korean males and females in both newborns and adults. (PMID:22531795)
• HLA-DRB5 was highly expressed in peripheral blood mononuclear cells from patients with systemic sclerosis-related interstitial lung disease. The HLA-DRB5*01:05 allele is a risk factor for interstitial lung disease in patients with systemic sclerosis. (PMID:22723597)
• DRB5*01:01 is associated with Thai systemic lupus erythematosus; the association is stronger than that of DRB1*15:01; genetic contribution of DRB5*01:01 is due partially to linkage disequilibrium between DRB1*16:02 and DRB5*01:01 in northern Thai population (PMID:22862923)
• Transgenic mice expressing HLA-DRB5*01:01 genes are crossed with histocompatibility class (MHC) II knockout mice to replace mouse MHC class II genes with human MHC class II genes in a humanized model of autoimmunity. (PMID:22888134)
• findings indicated that copy number variants of HLA-DRB5 was associated with the risk of systemic lupus erythematosus, and copy number deletion appeared to be protective for SLE. (PMID:24366815)
• Brain DNA methylation in HLA-DRB5 was associated with pathological Alzheimer disease. (PMID:25365775)
• HLA-DRB5 affects type 1 diabetes risk and islet autoantibodies. (PMID:26740600)
• This study identified genetic overlap between Alzheimer disease and immune-mediated diseases, implicating the HLA locus and IPMK in the pathobiology of Alzheimer disease. (PMID:27088644)
• Variation at HLA-DRB5 being associated both with Parkinson’s disease and Alzheimer’s disease, ariation at HLA-DRB5 being associated both with Parkinson’s disease and Alzheimer’s disease. (PMID:27713094)
• Case-control study in Han Chinese from the southwest of the country suggests that risk of ALS is increased by the AA genotype at rs9268856 in the HLA-DRA/HLA-DRB5 gene, but not by the SNPs rs9268877 in HLA-DRA/HLA-DRB5, rs1980493 in BTNL2 or rs302668 in RAB38/CTSC (PMID:28131168)
• In this study, molecular dynamics simulation was performed on the complexes of Top1 peptide with various HLA-DR subtypes divided into ATASSc-associated alleles (HLA-DRB1*08:02, HLA-DRB1*11:01 and HLA-DRB1*11:04), suspected allele (HLA-DRB5*01:02), and non-associated allele (HLA-DRB1*01:01). (PMID:30679605)
• Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia. (PMID:31624234)
• Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15. (PMID:31882398)
• Whole Exome Sequencing Identified Two Single Nucleotide Polymorphisms of Human Leukocyte Antigen-DRB5 in Familial Sarcoidosis in China. (PMID:36658707)
• Epigenome-wide methylation haplotype association analysis identified HLA-DRB1, HLA-DRB5 and HLA-DQB1 as risk factors for rheumatoid arthritis. (PMID:37688529)
• HLA DRB5 *01:01 is associated with pruritus in individuals with Fitzpatrick skin type IV-VI. (PMID:38104778)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2-Eb2	ENSMUSG00000067341

Paralogs (13): B2M (ENSG00000166710), HLA-DQB1 (ENSG00000179344), HLA-DRB1 (ENSG00000196126), HLA-DQA1 (ENSG00000196735), 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, DR beta 5 chain — Q30154 (reviewed: Q30154)

Alternative names: DR beta-5, DR2-beta-2, Dw2, MHC class II antigen DRB5

All UniProt accessions (3): A0A2Z4LKS3, A0AAQ5BI59, Q30154

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. Late endosome membrane.

Post-translational modifications. Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to down-regulation of MHC class II.

Polymorphism. The following alleles of DRB5 are known: DRB501:01, DRB501:02, DRB501:03, DRB501:04, DRB501:05, DRB501:06, DRB501:07, DRB501:09, DRB501:11, DRB501:12 DRB501:13, DRB501:14, DRB502:02, DRB502:03, DRB502:04, DRB502:05. The sequence shown is that of DRB5*01:01.

Similarity. Belongs to the MHC class II family.

RefSeq proteins (1): NP_002116* (*=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 (70 total): sequence variant 37, strand 12, helix 6, turn 3, disulfide bond 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1FV1	X-RAY DIFFRACTION	1.9
1ZGL	X-RAY DIFFRACTION	2.8
1H15	X-RAY DIFFRACTION	3.1
1HQR	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q30154-F1	87.62	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): 146–202, 44–108

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: 186 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, BIOCARTA_TCRA_PATHWAY, GCANCTGNY_MYOD_Q6, MODULE_64, GAURNIER_PSMD4_TARGETS, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, MODULE_143, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, KEGG_VIRAL_MYOCARDITIS

GO Biological Process (9): 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 immune response (GO:0050778), 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), 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), extracellular exosome (GO:0070062), 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
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 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
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
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	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

1842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HLA-DRB5	HLA-DRA	P01903	806
HLA-DRB5	PICALM	Q13492	714
HLA-DRB5	BTNL2	Q9UIR0	707
HLA-DRB5	ZCWPW1	Q9H0M4	698
HLA-DRB5	NME8	Q8N427	681
HLA-DRB5	ABCA7	Q8IZY2	673
HLA-DRB5	CASS4	Q9NQ75	672
HLA-DRB5	SLC24A4	Q8NFF2	642
HLA-DRB5	C8A	P07357	640
HLA-DRB5	GAK	O14976	626
HLA-DRB5	RIN3	Q8TB24	621
HLA-DRB5	SORL1	Q92673	620
HLA-DRB5	FERMT2	Q96AC1	609
HLA-DRB5	HLA-DMA	P28067	606
HLA-DRB5	CELF1	Q92879	594

IntAct

16 interactions, top by confidence:

A	B	Type	Score
HLA-DRA	HLA-DRB1	psi-mi:“MI:0914”(association)	0.880
HLA-DRB5	CHEK1	psi-mi:“MI:0914”(association)	0.560
HLA-DRB5	CHEK1	psi-mi:“MI:0915”(physical association)	0.560
HLA-DRB5	FXR1	psi-mi:“MI:0915”(physical association)	0.370
HLA-DRB1	CTDNEP1	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DRB5		psi-mi:“MI:0914”(association)	0.350
EPS15L1	AP2A2	psi-mi:“MI:0914”(association)	0.350
HLA-DRB5	tolC	psi-mi:“MI:0915”(physical association)	0.000
HLA-DRB5		psi-mi:“MI:0915”(physical association)	0.000
yscP	HLA-DRB5	psi-mi:“MI:0915”(physical association)	0.000
	HLA-DRB5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): HLA-DRB5 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), HLA-A (Affinity Capture-MS), STAT1 (Affinity Capture-MS), CHEK1 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), CHEK1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), HLA-DRB5 (Two-hybrid), HLA-DRB5 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS)

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

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CIITA	“up-regulates quantity by expression”	HLA-DRB5	“transcriptional regulation”
“RFX complex”	“up-regulates quantity by expression”	HLA-DRB5	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	10
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

725 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32518550:CCTCA:C	donor_loss	1.0000
6:32518551:CTCA:C	donor_loss	1.0000
6:32518552:TCAC:T	donor_loss	1.0000
6:32518553:CACCT:C	donor_loss	1.0000
6:32518555:C:T	donor_loss	1.0000
6:32518555:CCTTT:C	donor_gain	1.0000
6:32518662:TGCTC:T	acceptor_gain	1.0000
6:32518664:CTC:C	acceptor_gain	1.0000
6:32518665:TC:T	acceptor_gain	1.0000
6:32518666:CC:C	acceptor_gain	1.0000
6:32518666:CCTGG:C	acceptor_loss	1.0000
6:32518667:C:CA	acceptor_loss	1.0000
6:32518667:C:CC	acceptor_gain	1.0000
6:32519368:A:AC	donor_gain	1.0000
6:32519368:ACT:A	donor_gain	1.0000
6:32519369:C:CC	donor_gain	1.0000
6:32519369:CT:C	donor_gain	1.0000
6:32519369:CTC:C	donor_gain	1.0000
6:32520043:C:T	acceptor_gain	1.0000
6:32530123:A:AC	donor_gain	1.0000
6:32530124:C:CC	donor_gain	1.0000
6:32530124:CGT:C	donor_gain	1.0000
6:32517750:GTCC:G	acceptor_loss	0.9900
6:32517752:CCTG:C	acceptor_loss	0.9900
6:32517753:C:A	acceptor_loss	0.9900
6:32517754:T:C	acceptor_loss	0.9900
6:32518076:CC:C	acceptor_gain	0.9900
6:32518077:CC:C	acceptor_gain	0.9900
6:32518078:C:CC	acceptor_gain	0.9900
6:32518554:A:AC	donor_gain	0.9900

AlphaMissense

1732 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32519569:G:C	F151L	0.995
6:32519569:G:T	F151L	0.995
6:32519571:A:G	F151L	0.995
6:32519470:G:C	F184L	0.988
6:32519470:G:T	F184L	0.988
6:32519472:A:G	F184L	0.988
6:32519544:A:G	W160R	0.988
6:32519544:A:T	W160R	0.988
6:32522068:G:C	F69L	0.985
6:32522068:G:T	F69L	0.985
6:32522070:A:G	F69L	0.985
6:32519585:C:G	C146S	0.983
6:32519586:A:T	C146S	0.983
6:32519371:C:A	W217C	0.982
6:32519371:C:G	W217C	0.982
6:32519417:C:G	C202S	0.981
6:32519418:A:T	C202S	0.981
6:32519586:A:G	C146R	0.978
6:32519542:C:A	W160C	0.976
6:32519542:C:G	W160C	0.976
6:32519570:A:C	F151C	0.975
6:32519417:C:T	C202Y	0.974
6:32519570:A:G	F151S	0.974
6:32519404:G:C	H206Q	0.973
6:32519404:G:T	H206Q	0.973
6:32519418:A:G	C202R	0.973
6:32519585:C:T	C146Y	0.973
6:32521952:C:G	C108S	0.972
6:32521953:A:T	C108S	0.972
6:32519584:G:C	C146W	0.970

dbSNP variants (sampled 300 via entrez): RS1000878606 (6:32522494 C>T), RS1001168152 (6:32523792 G>A), RS1001724928 (6:32517653 G>A,T), RS1003190068 (6:32529767 A>T), RS1003428619 (6:32529680 T>C), RS1004098245 (6:32527596 G>T), RS1004741283 (6:32519899 G>A), RS1005414021 (6:32517899 A>T), RS1008014728 (6:32528230 C>A,G,T), RS1008140870 (6:32521400 A>G), RS1014017637 (6:32527573 A>G), RS1014877946 (6:32526023 T>C), RS1016852371 (6:32527598 C>T), RS1019319406 (6:32529075 C>A), RS1019960642 (6:32530930 A>G)

Disease associations

OMIM: gene MIM:604776 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

108 associations (top):

Study	Trait	p-value
GCST000311_1	Ulcerative colitis	1.000000e-16
GCST000906_3	Chronic lymphocytic leukemia	7.000000e-09
GCST000959_9	Parkinson’s disease	2.000000e-14
GCST000964_4	Ulcerative colitis	1.000000e-55
GCST001474_7	Hypothyroidism	5.000000e-07
GCST001826_10	Lymphoma	2.000000e-08
GCST001826_2	Lymphoma	3.000000e-12
GCST001826_3	Lymphoma	2.000000e-10
GCST001826_9	Lymphoma	3.000000e-06
GCST001942_21	Prostate cancer	5.000000e-09
GCST002094_1	Crohn’s disease	5.000000e-12
GCST002094_4	Crohn’s disease	3.000000e-12
GCST002217_4	Sjögren’s syndrome	9.000000e-37
GCST002245_18	Alzheimer’s disease (late onset)	3.000000e-12
GCST002516_2	Frontotemporal dementia	6.000000e-09
GCST002562_2	Vogt-Koyanagi-Harada syndrome	1.000000e-119
GCST002585_1	Antinuclear antibody levels	1.000000e-11
GCST003338_10	Waist-to-hip ratio adjusted for body mass index	4.000000e-08
GCST003338_2	Waist-to-hip ratio adjusted for body mass index	1.000000e-09
GCST003339_1	Epstein Barr virus nuclear antigen 1 IgG levels	1.000000e-11
GCST003339_2	Epstein Barr virus nuclear antigen 1 IgG levels	1.000000e-11
GCST003339_3	Epstein Barr virus nuclear antigen 1 IgG levels	6.000000e-06
GCST003339_6	Epstein Barr virus nuclear antigen 1 IgG levels	1.000000e-13
GCST003468_7	Chronic lymphocytic leukemia	6.000000e-16
GCST003984_21	Parkinson’s disease	4.000000e-17
GCST003987_2	Asthma	1.000000e-40
GCST003991_5	Childhood ear infection	1.000000e-11
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004268_1	Immune response to measles vaccine (measles-induced IFN gamma)	1.000000e-06

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007790	Epstein Barr virus nuclear antigen 1 IgG measurement
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0004645	response to vaccine
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0009184	heart rate response to exercise
EFO:0006941	grip strength measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0008579	risk-taking behaviour
EFO:0005413	joint damage measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3988561 (PROTEIN FAMILY)

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1071748	HLA-DRB5		0.00	0
rs184278615	HLA-DRB5		0.00	0
rs201469165	HLA-DRB5		0.00	0
rs192498095	HLA-DRB5		0.00	0

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
perfluorotetradecanoic acid	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sulforaphane	decreases expression	1
nickel chloride	affects cotreatment, increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorobutyric acid	increases expression	1
tamibarotene	increases expression	1
lumiracoxib	affects response to substance	1
MRK 003	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Arsenic	affects methylation	1
Cisplatin	affects expression, affects cotreatment	1
Cytarabine	decreases expression	1
Mitoxantrone	affects response to substance	1
Nicotine	increases expression, affects cotreatment	1
Palladium	affects response to substance	1
Polychlorinated Biphenyls	affects expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_V119	LDR2a	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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