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HLA-DRB5 major histocompatibility complex, class II, DR beta 5 [ Homo sapiens (human) ]

Gene ID: 3127, updated on 11-Jun-2021


Official Symbol
HLA-DRB5provided by HGNC
Official Full Name
major histocompatibility complex, class II, DR beta 5provided by HGNC
Primary source
See related
Ensembl:ENSG00000198502 MIM:604776
Gene type
protein coding
RefSeq status
Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
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. [provided by RefSeq, Feb 2020]
Broad expression in lung (RPKM 275.5), lymph node (RPKM 163.3) and 14 other tissues See more
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Genomic context

See HLA-DRB5 in Genome Data Viewer
Exon count:
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (32517343..32530316, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (32485130..32498064, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene major histocompatibility complex, class II, DR alpha Neighboring gene major histocompatibility complex, class II, DR beta 9 (pseudogene) Neighboring gene RNA, U1 small nuclear 61, pseudogene Neighboring gene major histocompatibility complex, class II, DR beta 6 (pseudogene)

Genomic regions, transcripts, and products


  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018


GeneRIFs: Gene References Into Functions

What's a GeneRIF?


Associated conditions

Description Tests
An association between anti-nuclear antibody and HLA class II locus and heterogeneous characteristics of staining patterns: The Nagahama Study.
GeneReviews: Not available
Frontotemporal dementia and its subtypes: a genome-wide association study.
GeneReviews: Not available
Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3.
GeneReviews: Not available
Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL.
GeneReviews: Not available
Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.
GeneReviews: Not available
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
GeneReviews: Not available
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
GeneReviews: Not available
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
GeneReviews: Not available
Novel associations for hypothyroidism include known autoimmune risk loci.
GeneReviews: Not available
Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.
GeneReviews: Not available
Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
GeneReviews: Not available

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env CD4-mediated endocytosis of HIV-1 gp120 results in MHC-II (HLA-DR) presentation to CD4+ T cells PubMed
env CD4+ T cells infected with CCR5-tropic HIV-1 have significantly higher levels of activation-marker expression (e.g. CD25, CD71 and HLA-DR) than CD4+ T lymphocytes infected with CXCR4-tropic HIV-1 PubMed
env HIV envelope protein gp120 can specifically inhibit CD4-dependent class II MHC-restricted T cell response to Ag PubMed
env Genetic variability in HIV-1 gp120 affects its interactions with HLA-DR molecules and T cell receptor PubMed
env Amino acid residues 42-49 in the V1 region of CD4 are involved in the interaction between HIV-1 gp120 and class II major histocompatibility complex molecules PubMed
Envelope surface glycoprotein gp160, precursor env Processing of HIV-1 gp160 to gp120 and gp41 is necessary for the association of HIV-1 envelope glycoproteins with class II MHC PubMed
env Antibodies against cell surface molecules LFA-1, ICAM-1, HLA-DR, and CD28 inhibit the HIV-1 gp160-induced B cell differentiation response; gp160 also induces IL-6R and CD23 molecule expression on B cells PubMed
Envelope transmembrane glycoprotein gp41 env Soluble HIV-1 gp41 can selectively enhance MHC class I and II expression on human B cells, but does not increase expression of other cell surface antigens such as CD21 and CD54 (ICAM-1) PubMed
env Soluble HIV-1 gp41 enhancement effects on MHC class I and II antigen expression can be inhibited by soluble gp41-binding proteins of 45, 49 and 62 kD from human B cells PubMed
env A 43-amino-acid sequence between amino acids 708 and 750 in the HIV-1 gp41(TM) cytoplasmic tail is required for efficient incorporation of HLA class II proteins into virions PubMed
Nef nef HIV-1 Nef impairs IL-4/GM-CSF-stimulated THP-1 differentiation towards immature DCs, which leads to the lower levels of CD11C, CD40, and HLA-DR protein expression from the cell surface PubMed
nef HIV-1 Nef-pulsed mDCs downregulate HLA-DR expression and upregulate CD25 and CCR7 expression in NK cells PubMed
nef Nef-triggered MHCII endocytosis requires Rab5 activity and lyst function, whereas lysosomal trafficking of internalized MHCII molecules requires Rab7 activity PubMed
nef Four large regions (residues 1-36, 66-97, 117-147, and 182-205) of HIV-1 Nef bind efficiently to eight HLA-DR molecules PubMed
Pr55(Gag) gag Expression of CD80, CD83, CD86, and HLA-DR molecules are significantly downregulated in mature dendritic cells after transduction with ubiquitinated Gag compared to unubiquitinated Gag constructs PubMed
gag Expression of MARCH-8 inhibits HLA-DR-mediated enhancement of mature Gag products internalization by downregulating cell surface HLA-DR PubMed
gag The Gag late-budding domain PTAP motif and the cytosolic tails of the HLA-DR alpha and beta chains are required for HLA-DR-mediated Gag accumulation in late endosomal/multivesicular bodies (LE/MVB) PubMed
gag Dynamin-dependent endocytosis is required for intracellular accumulation of HIV-1 Gag in presence of HLA-DR PubMed
gag Human Leukocyte Antigen DR (HLA-DR), Major Histocompatibility Complex class II molecules (MHC-II) induce a relocation of Gag to late endosomal/multivesicular bodies (LE/MVB) and increase the accumulation of viral particles assembling intracellularly PubMed
gag In human macrophages, HIV-1 Gag proteins co-localize with MHC II (HLA-DR), CD63, and Lamp1 in MHC II compartments PubMed
gag HIV-1 Gag virus-like particles efficiently activate human monocyte-derived dendritic cells (MDDC) and induce MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II PubMed
gag Two peptides of the CA domain of HIV-1 Gag, VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ, are presented on MHC II molecules of dendritic cells and have similar sensitivity for antigen-specific T cells PubMed
gag HIV-1 Gag virus-like particle-induced monocyte activation is shown by upregulation of molecules involved in antigen presentation (MHC II, CD80, CD86) and cell adhesion (CD54) PubMed
gag HIV-1 Gag expression is able to induce HLA-DR cell-surface localization in H78-C10.0 cells PubMed
Tat tat Treatment of PBMCs with HIV-1 Tat significantly enhances the generation of monocytic myeloid-derived suppressor cells expressing no or very low levels of HLA-DR PubMed
tat HIV-1 Tat upregulates HLA-DR expression in monocyte-derived dendritic cells and T cells, thereby driving T cell-mediated immune responses and activation PubMed
tat HIV-1 Tat downregulates expression of MHC class II genes in antigen-presenting cells (APC) by inhibiting the transactivator of MHC class II genes, CIITA PubMed
Vpu vpu HIV-1 Vpu interacts with CD74 and modulates MHC II in HIV-1-infected cells PubMed
capsid gag HIV-1 CA co-localizes with HLA-DR in human monocyte-derived dendritic cells PubMed
gag HIV-1 Capsid (p24) inhibits interferon gamma induced increases in HLA-DR and cytochrome B heavy chain mRNA levels in the human monocyte-like cell line THP1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem


Products Interactant Other Gene Complex Source Pubs Description

General gene information



Clone Names

  • FLJ76359

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables peptide antigen binding ISS
Inferred from Sequence or Structural Similarity
more info

General protein information

Preferred Names
major histocompatibility complex, class II, DR beta 5
DR beta-5
HLA class II histocompatibility antigen, DR-5 beta chain
MHC class II antigen DRB5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_002125.4NP_002116.2  major histocompatibility complex, class II, DR beta 5 precursor

    See identical proteins and their annotated locations for NP_002116.2

    Status: REVIEWED

    Source sequence(s)
    Consensus CDS
    ENSP00000364114.3, ENST00000374975.4
    Conserved Domains (2) summary
    MHC_II_beta; Class II histocompatibility antigen, beta domain
    IgC1_MHC_II_beta_HLA-DR; Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly


  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    32517343..32530316 complement
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011514562.2XP_011512864.1  major histocompatibility complex, class II, DR beta 5 isoform X1

    Conserved Domains (2) summary
    IgC_MHC_II_beta; Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain
    MHC_II_beta; Class II histocompatibility antigen, beta domain
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