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HLA-DRB4 Gene

protein-coding   GIFtS: 50
GCID: GC06M8R3846

Major Histocompatibility Complex, Class II, DR Beta 4


(Previous symbol: HLA-DR4B)
Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Major Histocompatibility Complex, Class II, DR Beta 41 2     HLA Class II Histocompatibility Antigen, DR Beta 4 Chain2
HLA-DR4B1 2     Human Leucocyte Antigen DRB42
MHC Class II Antigen DRB42 3     Leukocyte Antigen2
DR-42     MHC Class II Antigen HLA-DR-Beta2
DR42     MHC Class2 Antigen2
DRB42     MHC HLA DR-Beta Chain2
DRB1 Transplantation Antigen2     

External Ids:    HGNC: 49521   Entrez Gene: 31262   Ensembl: ENSG000002310217   UniProtKB: P137623   

Export aliases for HLA-DRB4 gene to outside databases

Previous GC identifers: GC06U990051 GC06P9R0072 GC06M032556 GC06M032076 GC06M032507 GC06Me32508 GC06M032657 GC06Pe32515 GC06Mf32600 GC06Mf32601 GC06Mm32579 GC06Mo32509 GC06Ml32465 GC06M8U3850


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for HLA-DRB4 Gene:
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 (APC: B lymphocytes, dendritic cells, macrophages). 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. DRB1 is expressed at a level five
times higher than its paralogues DRB3, DRB4 and DRB5. The presence of DRB4 is linked with allelic variants of
DRB1, otherwise it is omitted. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. (provided by
RefSeq, Jul 2008)

GeneCards Summary for HLA-DRB4 Gene:
HLA-DRB4 (major histocompatibility complex, class II, DR beta 4) is a protein-coding gene. Diseases associated with HLA-DRB4 include pityriasis rosea, and hemorrhagic fever with renal syndrome. GO annotations related to this gene include MHC class II receptor activity and peptide antigen binding.

UniProtKB/Swiss-Prot: DRB4_HUMAN, P13762
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

Gene Wiki entry for HLA-DRB4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for HLA-DRB4
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for HLA-DRB4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HLA-DRB4


Genomic Location:
Chromosome:6   

Entrez Gene cytogenetic band: 6p21.3   Ensembl cytogenetic band:  HSCHR6_MHC_MCFp21.32   HGNC cytogenetic band: 6p21.3 alternate reference locus

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06M8R3846:       (about GC identifiers)

Start:
3,850,430 bp from pter      End:
3,865,402 bp from pter
Size:
14,973 bases      Orientation:
minus strand

1 alternative location:
Chr6-,ALT_REF_LOCI_5 32,578,924-32,593,887     

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: DRB4_HUMAN, P13762 (See protein sequence)
Recommended Name: HLA class II histocompatibility antigen, DR beta 4 chain precursor  
Size: 266 amino acids; 29941 Da
Subunit: 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
Caution: HLA-DRB3, HLA-DRB4 and HLA-DRB5 may represent a unique gene
Secondary accessions: B0S863 O78042 P79664 Q29889 Q30163 Q6TLK6 Q860N4 Q861F3 Q8WLT9 Q9BS54

Explore the universe of human proteins at neXtProt for HLA-DRB4: NX_P13762

Explore proteomics data for HLA-DRB4 at MOPED

Post-translational modifications: 

  • Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of
    MHC class II. When associated with ubiquitination of the alpha subunit of HLA-DR: HLA-DRA 'Lys-244', the
    down-regulation of MHC class II may be highly effective1
  • Ubiquitination2 at Lys254
  • Glycosylation2 at Asn48
  • Modification sites at PhosphoSitePlus

  • See HLA-DRB4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_068818.4  
    ENSEMBL proteins: 
     ENSP00000412031  
    Reactome Protein details: P13762

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    HLA: Histocompatibility complex
    C1SET: Immunoglobulin superfamily / C1-set domain containing

    Selected InterPro protein domains (see all 7):
     IPR011162 MHC_I/II-like_Ag-recog
     IPR000353 MHC_II_b_N
     IPR013783 Ig-like_fold
     IPR014745 MHC_II_a/b_N
     IPR003597 Ig_C1-set

    Graphical View of Domain Structure for InterPro Entry P13762

    ProtoNet protein and cluster: P13762

    3 Blocks protein domains:
    IPB000353 Class II histocompatibility antigen
    IPB001003 MHC Class II alpha chain
    IPB003597 Immunoglobulin C-type


    UniProtKB/Swiss-Prot: DRB4_HUMAN, P13762
    Similarity: Belongs to the MHC class II family
    Similarity: Contains 1 Ig-like C1-type (immunoglobulin-like) domain


    HLA-DRB4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DRB4_HUMAN, P13762
    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

         Genatlas biochemistry entry for HLA-DRB4:
    HLA-DR,beta 4 chain,determining DRW53

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI15795121
    GO:0032395MHC class II receptor activity TAS10425186
    GO:0042605peptide antigen binding ISS--
         
    HLA-DRB4 for ontologies           About GeneDecksing


    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HLA-DRB4
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for HLA-DRB4

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    DRB4_HUMAN, P13762: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane;
    Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane
    protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane
    protein. Late endosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits
    through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for
    antigen presentation
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    endosome5
    lysosome5
    plasma membrane5
    vacuole5
    golgi apparatus4
    extracellular3
    nucleus1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005765lysosomal membrane TAS--
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane TAS10425186
    GO:0009897external side of plasma membrane ISS--

    HLA-DRB4 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for HLA-DRB4 About   (see all 25)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Allograft rejection
    Allograft rejection0.86
    Intestinal immune network for IgA production0.41
    Allograft Rejection0.86
    Viral myocarditis0.40
    Type I diabetes mellitus0.69
    CTL Mediated Apoptosis0.38
    Graft-versus-host disease0.65
    THC Differentiation Pathway0.38
    2CD28 co-stimulation
    Costimulation by the CD28 family0.44
    CTLA4 Signaling0.30
    3Translocation of ZAP-70 to Immunological synapse
    Translocation of ZAP-70 to Immunological synapse0.83
    PD-1 signaling0.72
    Phosphorylation of CD3 and TCR zeta chains0.83
    Generation of second messenger molecules0.62
    4Immune response Antigen presentation by MHC class II
    Immune response Antigen presentation by MHC class II0.46
    Immune response IL 22 signaling pathway0.31
    G protein signaling N RAS regulation pathway0.46
    5ICos-ICosL Pathway in T-Helper Cell
    ICos-ICosL Pathway in T-Helper Cell0.66
    Calcium Mediated T-Cell Apoptosis0.31
    CD28 Signaling in T-Helper Cell0.66

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for HLA-DRB4 (see all 12)
        THC Differentiation Pathway
    Calcium Mediated T-Cell Apoptosis
    IL-4 Pathway
    ICos-ICosL Pathway in T-Helper Cell
    CDC42 Pathway

    Selected GeneGo (Thomson Reuters) Pathways for HLA-DRB4 (see all 6)
        Immune response Antigen presentation by MHC class II
    Immune response ICOS pathway in T-helper cell
    Immune response T cell receptor signaling pathway
    Immune response IL-22 signaling pathway
    G-protein signaling N-RAS regulation pathway

    1 BioSystems Pathway for HLA-DRB4
        Allograft Rejection

    Selected Reactome Pathways for HLA-DRB4 (see all 7)
        Translocation of ZAP-70 to Immunological synapse
    Interferon gamma signaling
    Downstream TCR signaling
    PD-1 signaling
    MHC class II antigen presentation


    Selected Kegg Pathways  (Kegg details for HLA-DRB4) (see all 22):
        Phagosome
    Cell adhesion molecules (CAMs)
    Antigen processing and presentation
    Hematopoietic cell lineage
    Intestinal immune network for IgA production


    HLA-DRB4 for pathways           About GeneDecksing

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for HLA-DRB4
    Interactions:

        GeneGlobe Interaction Network for HLA-DRB4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for HLA-DRB4 (P137623 ENSP000004120314) via UniProtKB, MINT, STRING, and/or I2D (see all 61)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000228987P019033, ENSP000004104434I2D: score=1 STRING: ENSP00000410443
    ENSG00000206308P019033, ENSP000003727464I2D: score=1 STRING: ENSP00000372746
    ENSG00000226260P019033, ENSP000004045334I2D: score=1 STRING: ENSP00000404533
    ENSG00000227993P019033, ENSP000003726084I2D: score=1 STRING: ENSP00000372608
    ENSG00000234794P019033, ENSP000004052954I2D: score=1 STRING: ENSP00000405295
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002381immunoglobulin production involved in immunoglobulin mediated immune response ISS--
    GO:0002437inflammatory response to antigenic stimulus IDA15795121
    GO:0002455humoral immune response mediated by circulating immunoglobulin ISS--
    GO:0002862negative regulation of inflammatory response to antigenic stimulus IDA18039812
    GO:0006955immune response ISS--

    HLA-DRB4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for HLA-DRB4 (DRB4)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for HLA-DRB4 gene: 
    NM_021983.4  

    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000457451(uc011hzq.2)
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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      QuantiTect SYBR Green Assays in human, mouse, rat HLA-DRB4
      QuantiFast Probe-based Assays in human, mouse, rat HLA-DRB4

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    HLA-DRB4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GAGTTAAAAA
    HLA-DRB4 Expression
    About this image


    HLA-DRB4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     
     Blood (Hematopoietic System)
             Plasmacytoid Dendritic cells Peripheral Blood
    HLA-DRB4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HLA-DRB4 Protein Expression
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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HLA-DRB4

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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      --

    ENSEMBL Gene Tree for HLA-DRB4 (if available)
    TreeFam Gene Tree for HLA-DRB4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HLA-DRB4 gene
    Selected SIMAP similar genes for HLA-DRB4 using alignment to 24 protein entries:     DRB4_HUMAN (see all proteins) (see all similar genes):
    HLA-DRB4$0101    HLA DRB4    HLA-DRB1*0402    HLA-DRB1*0407    HLA-DRB1*1301    HLA-DRB1*1302
    HLA-DRB1*1402    HLA-DRB4*0102    DRB4    HLA-DRB4* variant allele    HLA-DR4/Dw13    HLA-DR-beta 1
    HLA-DRB13    HLA-D8.2V    HLA-DR4    HLA-DRBI    HLA-DRB1*1327    HLA-DR4I

    HLA-DRB4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    DRB4_HUMAN, P13762: The following alleles of DRB4 are known: DRB4*01:01, DRB4*01:02, DRB4*01:03, DRB4*01:04, DRB4*01:05,
    DRB4*01:06 and DRB4*01:07. The sequence shown is that of DRB4*01:03


    6 SNPs for HLA-DRB4    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0607804
    ----see VAR_0607802 Y H mis40--------
    rs32004051,2,4
    ----see VAR_0607832 mis40--------
    VAR_0607824
    ----see VAR_0607822 H Y mis40--------
    VAR_0607784
    ----see VAR_0607782 D G mis40--------
    VAR_0607814
    ----see VAR_0607812 G R mis40--------
    VAR_0607794
    ----see VAR_0607792 T N mis40--------

    HapMap Linkage Disequilibrium report for HLA-DRB4 (3850430 - 3865402 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for HLA-DRB4: --
    Human Gene Mutation Database (HGMD): HLA-DRB4
    Locus Specific Mutation Databases (LSDB): HLA-DRB4

    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing HLA-DRB4
    DNA2.0 Custom Variant and Variant Library Synthesis for HLA-DRB4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    Selected diseases for HLA-DRB4 (see all 74):    
    About MalaCards
    pityriasis rosea    hemorrhagic fever with renal syndrome    halo nevi    catastrophic antiphospholipid syndrome
    ascariasis    fetal and neonatal alloimmune thrombocytopenia    trichuriasis    mixed connective tissue disease
    juvenile rheumatoid arthritis    churg-strauss syndrome    antiphospholipid syndrome    guillain-barre syndrome
    connective tissue disease    diffuse panbronchiolitis    autoimmune hepatitis    hypersensitivity reaction type ii disease
    type 1 diabetes    toxoplasmosis    psoriatic arthritis    thrombotic thrombocytopenic purpura

    2 diseases from the University of Copenhagen DISEASES database for HLA-DRB4:
    Rheumatoid arthritis     Hypersensitivity reaction type II disease

    HLA-DRB4 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014

    3 Novoseek inferred disease relationships for HLA-DRB4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hashimotos thyroiditis 39.9 2 7744616 (1), 15055474 (1)
    mimicry 37.2 2 7536796 (1), 10397736 (1)
    autoimmune diseases 3.01 1 7536796 (1)

    Genetic Association Database (GAD): HLA-DRB4
    Human Genome Epidemiology (HuGE) Navigator: HLA-DRB4 (44 documents)

    Export disorders for HLA-DRB4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for HLA-DRB4 gene, integrated from 10 sources (see all 223):
    (articles sorted by number of sources associating them with HLA-DRB4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome. (PubMed id 17763415)1, 4, 9 Vaglio A....Neri T.M. (Arthritis Rheum. 2007)
    2. Specific amplification of the HLA-DRB4 gene from c-DNA. Complete coding sequence of the HLA alleles DRB4*0103101 and DRB4*01033. (PubMed id 11972878)1, 2, 9 De Pablo R.... Vilches C. (Tissue Antigens 2002)
    3. Interactions of HLA-DRB4 and CTLA-4 genes influence thyroid function in Hashimoto's thyroiditis in Japanese population. (PubMed id 15055474)1, 4, 9 Terauchi M....Saruta T. (J. Endocrinol. Invest. 2003)
    4. HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma. (PubMed id 15902698)1, 4, 9 Dorak M.T....Kaslow R.A. (J. Med. Virol. 2005)
    5. HLA-DR and DQB1 gene polymorphism in the North-western Colombian population. (PubMed id 12144632)1, 4, 9 Correa P.A....Anaya J.M. (Tissue Antigens 2002)
    6. Visual hallucinations and HLA class II antigens in cortical dementia. (PubMed id 20606439)1, 4 GA^mez-Tortosa E....CA!rdaba B. (Dement Geriatr Cogn Disord 2010)
    7. Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link. (PubMed id 19922436)1, 4 Scully M....Machin S. (J. Thromb. Haemost. 2010)
    8. The impact of anti-HY responses on outcome in current and subsequent pregnancies of patients with recurrent pregnancy losses. (PubMed id 20307907)1, 4 Christiansen O.B....Nielsen H.S. (J. Reprod. Immunol. 2010)
    9. Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy. (PubMed id 19223392)1, 4 Nielsen H.S....Christiansen O.B. (Hum. Mol. Genet. 2009)
    10. Long-range linkage on chromosome 6p of VEGF, FKBP5, HLA and TNF alleles associated with transplant rejection. (PubMed id 19233472)1, 4 Chen Y....Hutchinson I.V. (Mol. Immunol. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 3126 HGNC: 4952 Ensembl:ENSG00000231021 euGenes: HUgn3126 ECgene: HLA-DRB4 Kegg: 3126
    H-InvDB: HLA-DRB4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for HLA-DRB4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for HLA-DRB4 gene:
    Search GeneIP for patents involving HLA-DRB4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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