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    CD40 CD40 molecule [ Homo sapiens (human) ]

    Gene ID: 958, updated on 3-Dec-2024

    Summary

    Official Symbol
    CD40provided by HGNC
    Official Full Name
    CD40 moleculeprovided by HGNC
    Primary source
    HGNC:HGNC:11919
    See related
    Ensembl:ENSG00000101017 MIM:109535; AllianceGenome:HGNC:11919
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    p50; Bp50; CDW40; TNFRSF5
    Summary
    This gene is a member of the TNF-receptor superfamily. The encoded protein is a receptor on antigen-presenting cells of the immune system and is essential for mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency type 3 (HIGM3). Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2014]
    Expression
    Broad expression in lymph node (RPKM 19.2), appendix (RPKM 13.7) and 23 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CD40 in Genome Data Viewer
    Location:
    20q13.12
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (46118314..46129858)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (47854355..47865910)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (44746953..44758497)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17957 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr20:44717073-44717887 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:44717888-44718701 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17959 Neighboring gene nuclear receptor coactivator 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17960 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:44731180-44731415 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17962 Neighboring gene CRISPRi-FlowFISH-validated CD40 regulatory element GRCh37_chr20:44746135-44748232 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17965 Neighboring gene ribosomal protein L13 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17966 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17967 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44781551-44782092 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12973 Neighboring gene uncharacterized LOC124904916 Neighboring gene cadherin 22 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17968 Neighboring gene Sharpr-MPRA regulatory region 13247 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44844486-44845022 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:44845561-44846096 Neighboring gene MPRA-validated peak4226 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44886736-44887236 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44928578-44929078 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44929079-44929579 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:44932028-44932246 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44941853-44942801 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:44952422-44952611 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44966161-44966662 Neighboring gene Sharpr-MPRA regulatory region 3506 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:44979919-44980510 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:44980511-44981101 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:44985189-44985688 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12974 Neighboring gene solute carrier family 35 member C2

    Genomic regions, transcripts, and products

    Expression

    • 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

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Hyper-IgM syndrome type 3
    MedGen: C1720957 OMIM: 606843 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies three new risk loci for Kawasaki disease.
    EBI GWAS Catalog
    Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
    EBI GWAS Catalog
    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
    EBI GWAS Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20.
    EBI GWAS Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env The low mannose-level gp120 induces higher activation of plasmacytoid dendritic cells by upregulation of IFN-alpha, PD-L1, CD40, CCR7, CD80, and CD86 than the high mannose-level gp120 does PubMed
    env Inhibition of CpG-B-induced maturation of plasmacytoid dendritic cells by HIV-1 gp120 results in downregulation of CD40, CD83, CCR7, and HLA-DR expression PubMed
    env The binding of HIV-1 gp120 to CD4 molecules on T cells interrupts the sequential cascade of intercellular interactions involving antigen/MHC class II-TCR/CD4, CD40L-CD40, and B71-CD28 PubMed
    env HIV-1 gp120-induced reduction of IL-12 parallels IL-10 induction and inhibits translocation of CD40 to the surface of monocytes PubMed
    env Upregulation of apoptosis genes such as NCK-associated protein 1, PTB domain adaptor protein CED-6, and TNF receptor superfamily 5 are induced by HIV-1 gp120 in human neurons PubMed
    Pr55(Gag) gag CD40L expression on the surface of virus-like particles (VLPs) is to target HIV-1 Gag antigens to the CD40 receptor on dendritic cell (DCs) PubMed
    Tat tat Depletion of ARMS abrogates HIV-1 Tat-induced upregulation of CD40 expression in primary human microglia PubMed
    tat Recombinant CD40L synergizes with HIV-1 Tat to increase TNF-alpha release from primary human monocytes and microglia in an NF-kappaB-dependent manner. This synergism is attributed to a Tat-mediated up-regulation of CD40. PubMed
    tat HIV-1 Tat upregulates the expression of MHC and co-stimulatory molecules CD40, CD80, CD83 and CD86 in monocyte-derived dendritic cells, thereby driving T cell-mediated immune responses PubMed
    Vpr vpr HIV-1 Vpr downregulates the expression of several immunologically important molecules including CD40, CD80, CD83, and CD86 co-stimulatory molecules on monocyte-derived macrophage (MDM) and monocyte-derived dendritic cells (MDDC) PubMed
    Vpu vpu HIV-1 Vpu upregulates CD40 expression, which enhances efficient expression of VCAM-1 in endothelial cells PubMed
    matrix gag Treatment of human PBMCs with HIV-1 MA upregulates the expression of MCP-1, ICAM-1, CD40, CD86 and CD36 and downregulates the expression of nuclear receptors FXR and PPARgamma PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC9013

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables antigen binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein domain specific binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in B cell activation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in B cell mediated immunity IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in B cell proliferation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in CD40 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in CD40 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cell surface receptor signaling pathway via JAK-STAT IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to erythropoietin IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to interleukin-1 IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to tumor necrosis factor IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in defense response to protozoan IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in defense response to virus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in immune response-regulating cell surface receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in inflammatory response TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in intracellular calcium ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in platelet activation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of B cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of blood vessel endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of endothelial cell apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of interleukin-12 production IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of interleukin-4-mediated signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in positive regulation of isotype switching to IgG isotypes IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of protein kinase C signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein-containing complex assembly TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in response to cobalamin IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to type II interferon IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    part_of CD40 receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of CD40 receptor complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cell surface HDA PubMed 
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in intracellular membrane-bounded organelle IEA
    Inferred from Electronic Annotation
    more info
     
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
     
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in varicosity IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    tumor necrosis factor receptor superfamily member 5
    Names
    B cell surface antigen CD40
    B cell-associated molecule
    CD40 molecule, TNF receptor superfamily member 5
    CD40L receptor

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_007279.1 RefSeqGene

      Range
      4988..16479
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_40

    mRNA and Protein(s)

    1. NM_001250.6NP_001241.1  tumor necrosis factor receptor superfamily member 5 isoform 1 precursor

      See identical proteins and their annotated locations for NP_001241.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL035662, BC012419, BC064518, BM761221, BX364284
      Consensus CDS
      CCDS13393.1
      UniProtKB/Swiss-Prot
      E1P5S9, P25942, Q53GN5, Q5JY15, Q5U007, Q7M4Q8, Q86YK5, Q9BYU0
      UniProtKB/TrEMBL
      A0A0S2Z3C7
      Related
      ENSP00000361359.3, ENST00000372285.8
      Conserved Domains (1) summary
      cd13407
      Location:26186
      TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
    2. NM_001302753.2NP_001289682.1  tumor necrosis factor receptor superfamily member 5 isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL035662, BC012419, BC064518, BM761221, BX364284, BX364285
      Consensus CDS
      CCDS93053.1
      UniProtKB/TrEMBL
      A0A8Q3SI60
      Related
      ENSP00000512093.1, ENST00000695671.1
      Conserved Domains (1) summary
      cd13407
      Location:26186
      TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
    3. NM_001322421.2NP_001309350.1  tumor necrosis factor receptor superfamily member 5 isoform 4 precursor

      Status: REVIEWED

      Source sequence(s)
      AL035662, BX364284, HY063089
      Conserved Domains (1) summary
      cd13407
      Location:26186
      TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
    4. NM_001322422.2NP_001309351.1  tumor necrosis factor receptor superfamily member 5 isoform 5 precursor

      Status: REVIEWED

      Source sequence(s)
      AK222896, AL035662, BX364284, HY063089
      UniProtKB/TrEMBL
      A0A0S2Z349
      Conserved Domains (2) summary
      cd00185
      Location:62103
      TNFRSF; CRD2 [structural motif]
      cl22855
      Location:26135
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
    5. NM_001362758.2NP_001349687.1  tumor necrosis factor receptor superfamily member 5 isoform 6 precursor

      Status: REVIEWED

      Source sequence(s)
      AL035662
      UniProtKB/TrEMBL
      A0A8Q3WKP3
      Related
      ENSP00000512096.1, ENST00000489304.6
      Conserved Domains (1) summary
      cd13407
      Location:26186
      TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
    6. NM_001424339.1NP_001411268.1  tumor necrosis factor receptor superfamily member 5 isoform 7 precursor

      Status: REVIEWED

      Source sequence(s)
      AL035662
    7. NM_152854.4NP_690593.1  tumor necrosis factor receptor superfamily member 5 isoform 2 precursor

      See identical proteins and their annotated locations for NP_690593.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The resulting isoform (2) contains a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL035662, BC012419, BC064518, BM761221, BX364284
      Consensus CDS
      CCDS13394.1
      UniProtKB/TrEMBL
      A0A8Q3WKP3
      Related
      ENSP00000361350.3, ENST00000372276.7
      Conserved Domains (1) summary
      cd13407
      Location:26166
      TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40

    RNA

    1. NR_126502.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two internal exons and uses an alternate splice site in the 3' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK222896, AL035662, BC012419, BC064518, BX364284
      Related
      ENST00000620709.4
    2. NR_136327.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL035662, BX364284, HY063089

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      46118314..46129858
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017028135.2XP_016883624.1  tumor necrosis factor receptor superfamily member 5 isoform X1

    2. XM_017028136.2XP_016883625.1  tumor necrosis factor receptor superfamily member 5 isoform X2

    3. XM_011529109.3XP_011527411.1  tumor necrosis factor receptor superfamily member 5 isoform X5

      See identical proteins and their annotated locations for XP_011527411.1

      UniProtKB/TrEMBL
      H0YE23
      Related
      ENSP00000434825.1, ENST00000466205.5
      Conserved Domains (2) summary
      cd00185
      Location:62103
      TNFRSF; CRD2 [structural motif]
      cl22855
      Location:26135
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
    4. XM_047440601.1XP_047296557.1  tumor necrosis factor receptor superfamily member 5 isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      47854355..47865910
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054324242.1XP_054180217.1  tumor necrosis factor receptor superfamily member 5 isoform X1

    2. XM_054324243.1XP_054180218.1  tumor necrosis factor receptor superfamily member 5 isoform X2

    3. XM_054324246.1XP_054180221.1  tumor necrosis factor receptor superfamily member 5 isoform X5

      UniProtKB/TrEMBL
      H0YE23
    4. XM_054324245.1XP_054180220.1  tumor necrosis factor receptor superfamily member 5 isoform X4