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 repo... See more...

Aliases for CD40 Gene

Aliases for CD40 Gene

  • CD40 Molecule 2 3 5
  • Bp50 2 3 4
  • Tumor Necrosis Factor Receptor Superfamily Member 5 3 4
  • CD40 Molecule, TNF Receptor Superfamily Member 5 2 3
  • CD40L Receptor 3 4
  • TNFRSF5 3 4
  • P50 2 3
  • Tumor Necrosis Factor Receptor Superfamily, Member 5 2
  • B Cell Surface Antigen CD40 3
  • B-Cell Surface Antigen CD40 4
  • B Cell-Associated Molecule 3
  • CD40 Antigen 4
  • CDW40 3
  • CDw40 4
  • CD40 5

External Ids for CD40 Gene

Previous HGNC Symbols for CD40 Gene

  • TNFRSF5

Previous GeneCards Identifiers for CD40 Gene

  • GC20P044181
  • GC20P044746
  • GC20P041488

Summaries for CD40 Gene

Entrez Gene Summary for CD40 Gene

  • 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]

GeneCards Summary for CD40 Gene

CD40 (CD40 Molecule) is a Protein Coding gene. Diseases associated with CD40 include Immunodeficiency With Hyper-Igm, Type 3 and Immunodeficiency With Hyper-Igm, Type 1. Among its related pathways are Transcriptional misregulation in cancer and NF-KappaB Family Pathway. Gene Ontology (GO) annotations related to this gene include enzyme binding. An important paralog of this gene is TNFRSF11A.

UniProtKB/Swiss-Prot Summary for CD40 Gene

  • Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarity).

Gene Wiki entry for CD40 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CD40 Gene

Genomics for CD40 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CD40 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CD40 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CD40

Top Transcription factor binding sites by QIAGEN in the CD40 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun

Genomic Locations for CD40 Gene

Genomic Locations for CD40 Gene
chr20:46,118,242-46,129,863
(GRCh38/hg38)
Size:
11,622 bases
Orientation:
Plus strand
chr20:44,746,906-44,758,502
(GRCh37/hg19)
Size:
11,597 bases
Orientation:
Plus strand

Genomic View for CD40 Gene

Genes around CD40 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CD40 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CD40 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CD40 Gene

Proteins for CD40 Gene

  • Protein details for CD40 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P25942-TNR5_HUMAN
    Recommended name:
    Tumor necrosis factor receptor superfamily member 5
    Protein Accession:
    P25942
    Secondary Accessions:
    • E1P5S9
    • Q53GN5
    • Q5JY15
    • Q5U007
    • Q7M4Q8
    • Q86YK5
    • Q9BYU0

    Protein attributes for CD40 Gene

    Size:
    277 amino acids
    Molecular mass:
    30619 Da
    Quaternary structure:
    • Monomer and homodimer. The variant form found in the bladder carcinoma cell line Hu549 does not form homodimers. Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. Interacts with TRAF6 and MAP3K8; the interaction is required for ERK activation.

    Three dimensional structures from OCA and Proteopedia for CD40 Gene

    Alternative splice isoforms for CD40 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CD40 Gene

Post-translational modifications for CD40 Gene

  • Glycosylation at Asn153 and Asn180
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Antibody Products

  • Abcam antibodies for CD40

Protein Products

  • Abcam proteins for CD40

No data available for DME Specific Peptides for CD40 Gene

Domains & Families for CD40 Gene

Gene Families for CD40 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • CD markers
  • Disease related genes
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for CD40 Gene

InterPro:
Blocks:
  • TNFR/CD27/30/40/95 cysteine-rich region
  • FAS/CD95 receptor family signature
ProtoNet:

Suggested Antigen Peptide Sequences for CD40 Gene

GenScript: Design optimal peptide antigens:
  • CD40 protein (Q6P2H9_HUMAN)
  • CDw40 (TNR5_HUMAN)
genes like me logo Genes that share domains with CD40: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for CD40 Gene

Function for CD40 Gene

Molecular function for CD40 Gene

UniProtKB/Swiss-Prot Function:
Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarity).

Phenotypes From GWAS Catalog for CD40 Gene

Gene Ontology (GO) - Molecular Function for CD40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003823 antigen binding IEA,IBA 21873635
GO:0005515 protein binding IEA,IPI 7527023
GO:0019899 enzyme binding IPI 12223522
GO:0019904 protein domain specific binding IEA --
GO:0031625 ubiquitin protein ligase binding IPI 11279055
genes like me logo Genes that share ontologies with CD40: view
genes like me logo Genes that share phenotypes with CD40: view

Human Phenotype Ontology for CD40 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CD40 Gene

MGI Knock Outs for CD40:
  • Cd40 Cd40<tm1Kik>
  • Cd40 Cd40<tm1Arah>
  • Cd40 Cd40<tm1b(KOMP)Wtsi>
  • Cd40 Cd40<tm1Geha>

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CD40

Clone Products

  • Addgene plasmids for CD40

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CD40 Gene

Localization for CD40 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CD40 Gene

[Isoform I]: Cell membrane. Single-pass type I membrane protein.
[Isoform II]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CD40 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 3
endosome 3
cytosol 3
lysosome 3
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
golgi apparatus 2

Gene Ontology (GO) - Cellular Components for CD40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA --
GO:0005623 cell IEA --
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane ISS,TAS --
genes like me logo Genes that share ontologies with CD40: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CD40 Gene

Pathways & Interactions for CD40 Gene

PathCards logo

SuperPathways for CD40 Gene

SuperPathway Contained pathways
1 Allograft rejection
.44
.39
2 PEDF Induced Signaling
.57
.47
3 Toll-like Receptor Signaling Pathway
4 Akt Signaling
.60
.60
.55
5 4-1BB Pathway
.54
.42
genes like me logo Genes that share pathways with CD40: view

Pathways by source for CD40 Gene

1 GeneGo (Thomson Reuters) pathway for CD40 Gene
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway
15 Qiagen pathways for CD40 Gene
  • Akt Signaling
  • Antioxidant Action of Vitamin-C
  • CD40 Signaling
  • ICos-ICosL Pathway in T-Helper Cell
  • Molecular Mechanisms of Cancer

SIGNOR curated interactions for CD40 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for CD40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001934 positive regulation of protein phosphorylation IMP 21410936
GO:0002376 immune system process IEA --
GO:0002768 immune response-regulating cell surface receptor signaling pathway IEA,IBA 21873635
GO:0006874 cellular calcium ion homeostasis IMP 21410936
GO:0006954 inflammatory response TAS,IBA 21873635
genes like me logo Genes that share ontologies with CD40: view

Drugs & Compounds for CD40 Gene

(89) Drugs for CD40 Gene - From: DrugBank, ClinicalTrials, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
rituximab Approved Pharma Therapeutic Antibodies 2024
Simvastatin Approved Pharma Inhibitor, Competitive HMG-CoA reductase inhibitor 582
nivolumab Approved Pharma Therapeutic Antibodies, Immunotherapies 1165
Pembrolizumab Approved Pharma 1266
Dacetuzumab Investigational Pharma Target, antibody 9

(47) Additional Compounds for CD40 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CD40: view

Transcripts for CD40 Gene

mRNA/cDNA for CD40 Gene

6 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CD40

Clone Products

  • Addgene plasmids for CD40

Alternative Splicing Database (ASD) splice patterns (SP) for CD40 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8
SP1: - - -
SP2: - - - -
SP3: - - -
SP4: -

Relevant External Links for CD40 Gene

GeneLoc Exon Structure for
CD40

Expression for CD40 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CD40 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CD40 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (20.7), Breast (10.9), Platelet (10.2), and Gallbladder (9.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CD40 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CD40

SOURCE GeneReport for Unigene cluster for CD40 Gene:

Hs.472860

mRNA Expression by UniProt/SwissProt for CD40 Gene:

P25942-TNR5_HUMAN
Tissue specificity: B-cells and in primary carcinomas.

Evidence on tissue expression from TISSUES for CD40 Gene

  • Blood(4.8)
  • Kidney(4.6)
  • Lymph node(4.1)
  • Spleen(4)
  • Bone marrow(3.3)
  • Intestine(3.3)
  • Skin(3.1)
  • Heart(3.1)
  • Lung(3.1)
  • Liver(3.1)
  • Nervous system(2.8)
  • Muscle(2.8)
  • Pancreas(2.7)
  • Thyroid gland(2.6)
  • Stomach(2.4)
  • Bone(2.4)
  • Adrenal gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CD40 Gene

Germ Layers:
  • mesoderm
Systems:
  • immune
  • lymphatic
Regions:
General:
  • blood
  • bone marrow
  • lymph node
  • white blood cell
genes like me logo Genes that share expression patterns with CD40: view

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for CD40 Gene

Orthologs for CD40 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CD40 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CD40 30
  • 99.4 (n)
Dog
(Canis familiaris)
Mammalia CD40 30 31
  • 79.34 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CD40 30 31
  • 76.65 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Cd40 30 17 31
  • 71.29 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cd40 30
  • 70.56 (n)
Oppossum
(Monodelphis domestica)
Mammalia CD40 31
  • 55 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CD40 30 31
  • 52.58 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CD40 31
  • 37 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cd40 30
  • 47.77 (n)
Zebrafish
(Danio rerio)
Actinopterygii cd40 31
  • 25 (a)
ManyToMany
Species where no ortholog for CD40 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CD40 Gene

ENSEMBL:
Gene Tree for CD40 (if available)
TreeFam:
Gene Tree for CD40 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CD40: view image

Paralogs for CD40 Gene

(3) SIMAP similar genes for CD40 Gene using alignment to 3 proteins:

  • TNR5_HUMAN
  • H0YE23_HUMAN
  • Q6P2H9_HUMAN
genes like me logo Genes that share paralogs with CD40: view

Variants for CD40 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CD40 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
636399 Uncertain Significance: not provided 46,128,188(+) A/G MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
714820 Benign/Likely Benign: Hyper-IgM syndrome type 3; not provided 46,128,923(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT,THREE_PRIME_UTR_VARIANT
728215 Likely Benign: not provided 46,122,365(+) G/A INTRON_VARIANT
745831 Likely Benign: not provided 46,121,825(+) T/C NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
750493 Conflicting Interpretations: Hyper-IgM syndrome type 3; not provided 46,123,166(+) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for CD40 Gene

Structural Variations from Database of Genomic Variants (DGV) for CD40 Gene

Variant ID Type Subtype PubMed ID
esv2758796 CNV loss 17122850
nsv1057686 CNV loss 25217958
nsv1138961 CNV deletion 24896259
nsv586135 CNV loss 21841781
nsv833993 CNV gain 17160897

Variation tolerance for CD40 Gene

Residual Variation Intolerance Score: 58.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.02; 20.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CD40 Gene

Human Gene Mutation Database (HGMD)
CD40
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CD40

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CD40 Gene

Disorders for CD40 Gene

MalaCards: The human disease database

(79) MalaCards diseases for CD40 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search CD40 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TNR5_HUMAN
  • Immunodeficiency with hyper-IgM 3 (HIGM3) [MIM:606843]: A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections. {ECO:0000269 PubMed:11675497, ECO:0000269 PubMed:26545377}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CD40

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with CD40: view

No data available for Genatlas for CD40 Gene

Publications for CD40 Gene

  1. Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus. (PMID: 19421221) Malheiros D … Petzl-Erler ML (Genes and immunity 2009) 3 23 41
  2. Allelic variants of CD40 and CD40L genes interact to promote antibiotic-induced cutaneous allergic reactions. (PMID: 19735272) Kim SH … Adverse Drug Reaction Research Group in Korea (Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2009) 3 23 41
  3. [Association between inflammatory cytokine CD40 gene polymorphism and risk of acute coronary syndrome]. (PMID: 19099972) Tian CX … Huang CX (Zhonghua xin xue guan bing za zhi 2008) 3 23 41
  4. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. (PMID: 18794853) Raychaudhuri S … Plenge RM (Nature genetics 2008) 3 23 41
  5. Association analysis of CD40 polymorphisms with asthma and the level of serum total IgE. (PMID: 17255560) Park JH … Shin HD (American journal of respiratory and critical care medicine 2007) 3 23 41

Products for CD40 Gene