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CD40 CD40 molecule [ Homo sapiens (human) ]

Gene ID: 958, updated on 5-Dec-2021

Summary

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Official Symbol
CD40provided by HGNC
Official Full Name
CD40 moleculeprovided by HGNC
Primary source
HGNC:HGNC:11919
See related
Ensembl:ENSG00000101017 MIM:109535
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
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Genomic context

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See CD40 in Genome Data Viewer
Location:
20q13.12
Exon count:
9
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 20 NC_000020.11 (46118242..46129858)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (44746953..44758497)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene nuclear receptor coactivator 5 Neighboring gene ribosomal protein L13 pseudogene 2 Neighboring gene cadherin 22 Neighboring gene solute carrier family 35 member C2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population. Huang Q, et al. Front Immunol, 2021. PMID 33968033, Free PMC Article
  2. Transcriptional Regulation of CD40 Expression by 4 Ribosomal Proteins via a Functional SNP on a Disease-Associated CD40 Locus. Zou M, et al. Genes (Basel), 2020 Dec 21. PMID 33371207, Free PMC Article
  3. Association of CD40 rs1883832 Polymorphism with Susceptibility of Diabetic Nephropathy and Neuropathy in Egyptian Population. Ghareeb D, et al. Egypt J Immunol, 2020 Jan. PMID 33180391
  4. CD40 DNA hypermethylation in primary gastric tumors; as a novel diagnostic biomarker. Amini M, et al. Life Sci, 2020 Aug 1. PMID 32407843
  5. Association of soluble CD40 levels with -1 C > T CD40 polymorphism and chronic kidney disease in systemic lupus erythematosus. Tapia-Llanos R, et al. Mol Genet Genomic Med, 2019 Dec. PMID 31642196, Free PMC Article

See all (595) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. [The CD40-CD40L axis: Current and future implications in clinical immunology].", trans "L'axe CD40-CD40L : implications actuelles et futures en immunologie clinique.
    Title: [The CD40-CD40L axis: Current and future implications in clinical immunology].
  2. CD40 Activity on Mesenchymal Cells Negatively Regulates OX40L to Maintain Bone Marrow Immune Homeostasis Under Stress Conditions.
    Title: CD40 Activity on Mesenchymal Cells Negatively Regulates OX40L to Maintain Bone Marrow Immune Homeostasis Under Stress Conditions.
  3. Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population.
    Title: Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population.
  4. Transcriptional Regulation of CD40 Expression by 4 Ribosomal Proteins via a Functional SNP on a Disease-Associated CD40 Locus.
    Title: Transcriptional Regulation of <i>CD40</i> Expression by 4 Ribosomal Proteins via a Functional SNP on a Disease-Associated <i>CD40</i> Locus.
  5. Polymorphisms of the genes CTLA4, PTPN22, CD40, and PPARG and their roles in Graves' disease: susceptibility and clinical features.
    Title: Polymorphisms of the genes CTLA4, PTPN22, CD40, and PPARG and their roles in Graves' disease: susceptibility and clinical features.
  6. CD40 and CD72 expression and prognostic values among children with systemic lupus erythematosus: a case-control study.
    Title: CD40 and CD72 expression and prognostic values among children with systemic lupus erythematosus: a case-control study.
  7. Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of IL7R, LAG3, and CD40 Genes in a Jordanian Population: A Genotype-Phenotype Study.
    Title: Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of <i>IL7R, LAG3</i>, and <i>CD40</i> Genes in a Jordanian Population: A Genotype-Phenotype Study.
  8. Functional association of a CD40 gene single-nucleotide polymorphism with the pathogenesis of coronary heart disease.
    Title: Functional association of a CD40 gene single-nucleotide polymorphism with the pathogenesis of coronary heart disease.
  9. Association of CD40 rs1883832 Polymorphism with Susceptibility of Diabetic Nephropathy and Neuropathy in Egyptian Population.
    Title: Association of CD40 rs1883832 Polymorphism with Susceptibility of Diabetic Nephropathy and Neuropathy in Egyptian Population.
  10. The CD40-ATP-P2X 7 Receptor Pathway: Cell to Cell Cross-Talk to Promote Inflammation and Programmed Cell Death of Endothelial Cells.
    Title: The CD40-ATP-P2X <sub><i>7</i></sub> Receptor Pathway: Cell to Cell Cross-Talk to Promote Inflammation and Programmed Cell Death of Endothelial Cells.
Submit: New GeneRIF Correction See all GeneRIFs (437)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
A genome-wide association study identifies three new risk loci for Kawasaki disease.
GeneReviews: Not available
Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
GeneReviews: Not available
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
GeneReviews: Not available
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
GeneReviews: Not available
Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20.
GeneReviews: Not available
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
GeneReviews: Not available
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.
GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GeneReviews: Not available
Hyper-IgM syndrome type 3
MedGen: C1720957 OMIM: 606843 GeneReviews: Not available
Compare labs
Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis.
GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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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

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC9013

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables antigen binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor activity IEA
Inferred from Electronic Annotation
more info
  
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
 PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in CD40 signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in TRIF-dependent toll-like receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in cellular calcium ion homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to interleukin-1 IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in cellular response to tumor necrosis factor IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in defense response to protozoan IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in defense response to virus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in immune response-regulating cell surface receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in platelet activation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in positive regulation of B cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of GTPase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in positive regulation of MAP kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of angiogenesis IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
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 endothelial cell apoptotic process IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of isotype switching to IgG isotypes IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of protein kinase C signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of tyrosine phosphorylation of STAT protein IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of tyrosine phosphorylation of STAT protein IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein kinase B signaling IEA
Inferred from Electronic Annotation
more info
  
involved_in protein-containing complex assembly TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to interferon-gamma IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
Component Evidence Code Pubs
part_of CD40 receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
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
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in integral component of plasma membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in intracellular membrane-bounded organelle 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
  

General protein information

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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)

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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.

Genomic

  1. NG_007279.1 RefSeqGene

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

mRNA and Protein(s)

  1. NM_001250.6 → NP_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
    P25942
    UniProtKB/TrEMBL
    A0A0S2Z3C7, Q6P2H9
    Related
    ENSP00000361359.3, ENST00000372285.8
    Conserved Domains (1) summary
    cd13407
    Location:26 → 186
    TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40

  2. NM_001302753.2 → NP_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
    UniProtKB/Swiss-Prot
    P25942
    UniProtKB/TrEMBL
    Q6P2H9
    Conserved Domains (1) summary
    cd13407
    Location:26 → 186
    TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40

  3. NM_001322421.2 → NP_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:26 → 186
    TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40

  4. NM_001322422.2 → NP_001309351.1  tumor necrosis factor receptor superfamily member 5 isoform 5 precursor

    Status: REVIEWED

    Source sequence(s)
    AK222896, AL035662, BX364284, HY063089
    UniProtKB/Swiss-Prot
    P25942
    UniProtKB/TrEMBL
    A0A0S2Z349
    Conserved Domains (2) summary
    cd00185
    Location:62 → 103
    TNFRSF; CRD2 [structural motif]
    cl22855
    Location:26 → 135
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

  5. NM_001362758.2 → NP_001349687.1  tumor necrosis factor receptor superfamily member 5 isoform 6 precursor

    Status: REVIEWED

    Source sequence(s)
    AL035662
    Conserved Domains (1) summary
    cd13407
    Location:26 → 186
    TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40

  6. NM_152854.4 → NP_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/Swiss-Prot
    P25942
    UniProtKB/TrEMBL
    Q6P2H9
    Related
    ENSP00000361350.3, ENST00000372276.7
    Conserved Domains (1) summary
    cd13407
    Location:26 → 166
    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: Homo sapiens Updated Annotation Release 109.20211119

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p13 Primary Assembly

    Range
    46118242..46129858
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

  2. XM_005260619.3 → XP_005260676.1  tumor necrosis factor receptor superfamily member 5 isoform X3

    Conserved Domains (2) summary
    cd00185
    Location:62 → 103
    TNFRSF; CRD2 [structural motif]
    cl22855
    Location:26 → 135
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

  3. XM_011529109.2 → XP_011527411.1  tumor necrosis factor receptor superfamily member 5 isoform X5

    See identical proteins and their annotated locations for XP_011527411.1

    Related
    ENSP00000434825.1, ENST00000466205.5
    Conserved Domains (2) summary
    cd00185
    Location:62 → 103
    TNFRSF; CRD2 [structural motif]
    cl22855
    Location:26 → 135
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

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

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P25942.1 GenPept UniProtKB/Swiss-Prot:P25942

Gene LinkOut

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