| HGNC Family | Immunoglobulin superfamily domain containing, Histocompatibility complex (HLA) |
| Name | major histocompatibility complex, class II, DR beta 4 |
| Description | HLA-DRB4 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] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHLA‐DRB4, one of the non‐classical HLA class II molecules, plays divergent roles in modulating immune responses across a spectrum of diseases. In autoimmune disorders, its influence appears context‐dependent. In Hashimoto’s thyroiditis, for example, an increased frequency of the DRB4*0101 allele has been associated with elevated thyroid‐stimulating hormone levels and enhanced thyroid dysfunction, suggesting a contributory role in disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, investigations in psoriasis vulgaris have revealed a significantly lower prevalence of DRB4*01 in patients compared with controls, consistent with a protective effect."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, studies in narcolepsy‐cataplexy have demonstrated that DRB4 expression is strongly protective, while in vitiligo the DRB4*010101 allele is markedly increased, indicating a susceptibility factor in certain organ‐specific autoimmunities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside the classical autoimmunity arena, HLA‐DRB4 has also been implicated in modulating risks in metabolic and hematologic disorders. In acute myelogenous leukemia, the DRB4 allele is significantly under‐represented in patients compared to controls, suggesting that its presence might be protective."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Conversely, in type 1 diabetes, the specific allele DRB4*01:03:01 shows one of the strongest associations with disease risk—with its effect further modulated by linked HLA‐DRB1 alleles—underscoring its role as a genetic risk marker in this complex disorder."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, in neurologic autoimmunity, particularly in patients with non‐tumor anti‐LGI1 encephalitis, HLA‐DRB4 is uniformly present, reinforcing its potential utility as a biomarker for autoimmune pathogenesis in this condition and highlighting its value in distinguishing patient subgroups that may require different management approaches."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Terauchi, T Yanagawa, N Ishikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactions of HLA-DRB4 and CTLA-4 genes influence thyroid function in Hashimoto's thyroiditis in Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/BF03349159"}], "href": "https://doi.org/10.1007/BF03349159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15055474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15055474"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M Tevfik Dorak, Leland J Yee, Jianming Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Virol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jmv.20361"}], "href": "https://doi.org/10.1002/jmv.20361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15902698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15902698"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Claudia Bueno Cardoso, Ana Maria Uthida-Tanaka, Renata Ferreira Magalhães, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Dermatol (2005)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15908298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15908298"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Eun Youn Roh, Myoung Hee Park, Hyejin Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HLA-DR and -DQ genes with narcolepsy in Koreans: comparison with two control groups, randomly selected subjects and DRB1"}, {"type": "i", "children": [{"type": "t", "text": "1501-DQB1"}]}, {"type": "t", "text": "0602--positive subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humimm.2006.03.024"}], "href": "https://doi.org/10.1016/j.humimm.2006.03.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17002906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17002906"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Abdullah Abanmi, Fahad Al Harthi, Riyadh Al Baqami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HLA loci alleles and antigens in Saudi patients with vitiligo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Dermatol Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00403-006-0699-4"}], "href": "https://doi.org/10.1007/s00403-006-0699-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17021767"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17021767"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Farideh Khosravi, Aliakbar Amirzargar, Abdolfatah Sarafnejad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HLA class II allele and haplotype frequencies in Iranian patients with leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Iran J Allergy Asthma Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "06.03/ijaai.137142"}], "href": "https://doi.org/06.03/ijaai.137142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17893434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17893434"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lue Ping Zhao, Shehab Alshiekh, Michael Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db15-1115"}], "href": "https://doi.org/10.2337/db15-1115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26740600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26740600"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Agnes van Sonderen, Dave L Roelen, Johannes A Stoop, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.24858"}], "href": "https://doi.org/10.1002/ana.24858"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28026046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28026046"}]}]}]}
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| Synonyms | DR4, DRB4, HLA-DR4B, DR-4 |
| Proteins | DRB4_HUMAN |
| NCBI Gene ID | 3126 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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HLA-DRB4 has 2,201 functional associations with biological entities spanning 7 categories (organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 56 datasets.
Click the + buttons to view associations for HLA-DRB4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by HLA-DRB4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of HLA-DRB4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of HLA-DRB4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of HLA-DRB4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of HLA-DRB4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of HLA-DRB4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing HLA-DRB4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with HLA-DRB4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with HLA-DRB4 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with HLA-DRB4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with HLA-DRB4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with HLA-DRB4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with HLA-DRB4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing HLA-DRB4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with HLA-DRB4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with HLA-DRB4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of HLA-DRB4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with HLA-DRB4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing HLA-DRB4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of HLA-DRB4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of HLA-DRB4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of HLA-DRB4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of HLA-DRB4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of HLA-DRB4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of HLA-DRB4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving HLA-DRB4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving HLA-DRB4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving HLA-DRB4 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing HLA-DRB4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing HLA-DRB4 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing HLA-DRB4 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by HLA-DRB4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by HLA-DRB4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with HLA-DRB4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with HLA-DRB4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with HLA-DRB4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for HLA-DRB4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of HLA-DRB4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways | pathways involving HLA-DRB4 protein from the KEGG Pathways dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of HLA-DRB4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with HLA-DRB4 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing HLA-DRB4 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain HLA-DRB4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of HLA-DRB4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for HLA-DRB4 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving HLA-DRB4 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2014 | pathways involving HLA-DRB4 protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving HLA-DRB4 protein from the Reactome Pathways 2024 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of HLA-DRB4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of HLA-DRB4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sanger Dependency Map Cancer Cell Line Proteomics | cell lines associated with HLA-DRB4 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of HLA-DRB4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of HLA-DRB4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of HLA-DRB4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with HLA-DRB4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| WikiPathways Pathways 2014 | pathways involving HLA-DRB4 protein from the Wikipathways Pathways 2014 dataset. | |
