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    CD40LG CD40 ligand [ Homo sapiens (human) ]

    Gene ID: 959, updated on 11-May-2013
    Official Symbol
    CD40LGprovided by HGNC
    Official Full Name
    CD40 ligandprovided by HGNC
    Primary source
    HGNC:11935
    Locus tag
    RP3-527F8.3
    See related
    Ensembl:ENSG00000102245; HPRD:02311; MIM:300386; Vega:OTTHUMG00000022512
    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
    IGM; IMD3; TRAP; gp39; CD154; CD40L; HIGM1; T-BAM; TNFSF5; hCD40L
    Summary
    The protein encoded by this gene is expressed on the surface of T cells. It regulates B cell function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper-IgM syndrome. [provided by RefSeq, Jul 2008]
    Location :
    Xq26
    Sequence :
    Chromosome: X; NC_000023.10 (135730336..135742549)
    See CD40LG in Epigenomics, MapViewer

    Chromosome X - NC_000023.10Genomic Context describing neighboring genes Neighboring gene vestigial like 1 (Drosophila) Neighboring gene microRNA 934 Neighboring gene uncharacterized LOC100128420 Neighboring gene Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 Neighboring gene solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6 pseudogene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    Immunodeficiency with hyper IgM type 1

    Summary from GeneReviews: X-Linked Hyper IgM Syndrome Go to GeneReviews

    Disease Characteristics
    X-linked hyper IgM syndrome (HIGM1), a disorder of abnormal T- and B-cell function, is characterized by low serum concentrations of IgG and IgA and normal or elevated serum concentrations of IgM. Mitogen proliferation may be normal, but NK- and T-cell cytotoxicity are frequently impaired. Antigen-specific responses may be decreased or absent. The range of clinical findings varies, even within the same family. Over 50% of males with HIGM1 develop symptoms by age one year, and more than 90% are symptomatic by age four years. HIGM1 usually presents in infancy with recurrent upper- and lower-respiratory tract bacterial infections, opportunistic infections, and recurrent or protracted diarrhea associated with failure to thrive. Neutropenia, thrombocytopenia, and anemia are common. Autoimmune and/or inflammatory disorders, such as sclerosing cholangitis, have been reported. Significant neurologic complications, often the result of a CNS infection, are seen in 10%-15% of affected males. Liver disease, including primary cirrhosis and carcinomas (bile duct carcinomas, hepatocellular carcinomas, adenocarcinomas of the liver and gall bladder), and tumors of the gastrointestinal tract (carcinoid of the pancreas, glucagonoma of the pancreas) are common life-threatening complications in adolescents and young adults with HIGM1. Affected males also have an increased risk for lymphoma, particularly Hodgkin's disease associated with Epstein-Barr virus infection.
    Diagnosis Testing
    The diagnosis of HIGM1 is based on a combination of clinical findings, family history, absent or decreased expression of the CD40 ligand (CD40L) protein on flow cytometry following in vitro stimulation of white cells, and molecular genetic testing of CD40LG (previously known as TNFSF5 or CD154), the only gene in which mutations are known to cause HIGM1. Direct sequencing of the entire coding region and intron/exon boundaries detects mutations in approximately 95% of affected males.
    Genetic Counseling
    X-linked hyper IgM syndrome (HIGM1) is inherited in an X-linked manner. Female carriers are asymptomatic and have no immunologic or biochemical markers of the disorder. Female carriers have a 50% chance of transmitting the disease-causing mutation in each pregnancy; males who inherit the mutation will be affected; females who inherit the mutation will be carriers. Affected males pass the disease-causing mutation to all their daughters and none of their sons. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation has been identified in the family.
    References
    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 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
    Gag, Pr55 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
    Nef, p27 nef HIV-1 Nef suppresses immunoglobulin class-switch DNA recombination by inducing IkappaBalpha and SOCS proteins, which block CD154, IL-4 and IL-10 cytokine signaling via NF-kappaB and STAT transcription factors PubMed
    nef A significant increase is observed in polyfunctional Nef-specific CD4 T cells expressing CD154 after vaccination with the modified vaccinia virus Ankara (MVA)-expressing HIV-1 nef PubMed
    Tat, p14 tat HIV-1 Tat-induced platelet activation leads to release of the platelet CD154 (CD40L), an immune modulator 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

    Go to the HIV-1, Human Protein Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description
    P29965 P25942 CD40    HPRD  PubMed  
    P29965 P29965 CD40LG    HPRD  PubMed  
    P29965 O43866 CD5L    HPRD  PubMed  
    P29965 P01857 IGHG1    HPRD  PubMed  
    P29965 P01834 IGKC    HPRD  PubMed  
    P29965 P04637 TP53    HPRD  PubMed  
    BioGRID:107397 BioGRID:106832 APOA1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107397 BioGRID:107800 CRYAB    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107397 BioGRID:109487 HPR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107397 BioGRID:122731 RNF128    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:107397 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-Western 
    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Allograft rejection, organism-specific biosystem (from KEGG)
      Allograft rejection, organism-specific biosystemAllograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. After transplantation of organ allografts, there are two pathways of anti...
    • Allograft rejection, conserved biosystem (from KEGG)
      Allograft rejection, conserved biosystemAllograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. After transplantation of organ allografts, there are two pathways of anti...
    • Asthma, organism-specific biosystem (from KEGG)
      Asthma, organism-specific biosystemAsthma is a complex syndrome with many clinical phenotypes in both adults and children. Its major characteristics include a variable degree of airflow obstruction, bronchial hyperresponsiveness, and ...
    • Asthma, conserved biosystem (from KEGG)
      Asthma, conserved biosystemAsthma is a complex syndrome with many clinical phenotypes in both adults and children. Its major characteristics include a variable degree of airflow obstruction, bronchial hyperresponsiveness, and ...
    • Autoimmune thyroid disease, organism-specific biosystem (from KEGG)
      Autoimmune thyroid disease, organism-specific biosystemThe classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroidi...
    • Autoimmune thyroid disease, conserved biosystem (from KEGG)
      Autoimmune thyroid disease, conserved biosystemThe classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroidi...
    • CD40/CD40L signaling, organism-specific biosystem (from Pathway Interaction Database)
      CD40/CD40L signaling, organism-specific biosystem
      CD40/CD40L signaling
    • Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
      Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem
      Calcineurin-regulated NFAT-dependent transcription in lymphocytes
    • Calcium signaling in the CD4+ TCR pathway, organism-specific biosystem (from Pathway Interaction Database)
      Calcium signaling in the CD4+ TCR pathway, organism-specific biosystem
      Calcium signaling in the CD4+ TCR pathway
    • Cell adhesion molecules (CAMs), organism-specific biosystem (from KEGG)
      Cell adhesion molecules (CAMs), organism-specific biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Cell adhesion molecules (CAMs), conserved biosystem (from KEGG)
      Cell adhesion molecules (CAMs), conserved biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • IL4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL4-mediated signaling events, organism-specific biosystem
      IL4-mediated signaling events
    • Id Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Id Signaling Pathway, organism-specific biosystemInhibitor of DNA binding (ID) proteins are members of the helix-loop-helix (HLH) family of proteins which lack a DNA binding domain themselves but bind to other family members inhibiting their DNA bi...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
      Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
    • Inflammatory Response Pathway, organism-specific biosystem (from WikiPathways)
      Inflammatory Response Pathway, organism-specific biosystem
      Inflammatory Response Pathway
    • Intestinal immune network for IgA production, organism-specific biosystem (from KEGG)
      Intestinal immune network for IgA production, organism-specific biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Intestinal immune network for IgA production, conserved biosystem (from KEGG)
      Intestinal immune network for IgA production, conserved biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Malaria, organism-specific biosystem (from KEGG)
      Malaria, organism-specific biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
    • Malaria, conserved biosystem (from KEGG)
      Malaria, conserved biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
    • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
      NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
    • Primary immunodeficiency, organism-specific biosystem (from KEGG)
      Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
    • Primary immunodeficiency, conserved biosystem (from KEGG)
      Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
    • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
      Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
    • Systemic lupus erythematosus, conserved biosystem (from KEGG)
      Systemic lupus erythematosus, conserved biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • Toxoplasmosis, organism-specific biosystem (from KEGG)
      Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
    • Toxoplasmosis, conserved biosystem (from KEGG)
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    • Viral myocarditis, organism-specific biosystem (from KEGG)
      Viral myocarditis, organism-specific biosystemMyocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is stil...

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    CD40 receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    cytokine activity IEA
    Inferred from Electronic Annotation
    more info
     
    tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    B cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    B cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    immunoglobulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    isotype switching ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    leukocyte cell-cell adhesion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    platelet activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of endothelial cell apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of interleukin-12 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of immune response TAS
    Traceable Author Statement
    more info
     
    regulation of immunoglobulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    integral to membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    integral to plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    CD40 ligand
    Names
    CD40 ligand
    CD40-L
    CD40 antigen ligand
    T-cell antigen Gp39
    T-B cell-activating molecule
    TNF-related activation protein
    tumor necrosis factor (ligand) superfamily member 5

    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_007280.1 RefSeqGene

      Range
      5001..17214
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_141

    mRNA and Protein(s)

    1. NM_000074.2NP_000065.1  CD40 ligand

      Status: REVIEWED

      Source sequence(s)
      BC071754, X67878
      Consensus CDS
      CCDS14659.1
      UniProtKB/Swiss-Prot
      P29965
      Related
      ENSP00000359663, OTTHUMP00000024130, ENST00000370629, OTTHUMT00000058501
      Conserved Domains (1) summary
      cd00184
      Location:122259
      Blast Score: 268
      TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000023.10 Reference GRCh37.p10 Primary Assembly

      Range
      135730336..135742549
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000155.1 Alternate HuRef

      Range
      125001305..125013640
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018934.1 Alternate CHM1_1.0

      Range
      135688733..135701039
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

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