CD40LG
CD40 ligand, the group of CD molecules|Tumor necrosis factor superfamily
Basic information
Region (hg38): X:136648158-136660390
Previous symbols: [ "HIGM1", "IMD3", "TNFSF5" ]
Links
Phenotypes
GenCC
Source:
- hyper-IgM syndrome type 1 (Definitive), mode of inheritance: XL
- hyper-IgM syndrome type 1 (Supportive), mode of inheritance: XL
- hyper-IgM syndrome type 1 (Definitive), mode of inheritance: XL
- hyper-IgM syndrome type 1 (Strong), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency, with hyper-IgM, type 1 | XL | Allergy/Immunology/Infectious; Oncologic | Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been described as being at increased risk of malignancy, and awareness may allow early detection and management; BMT has been reported | Allergy/Immunology/Infectious; Hematologic; Oncologic | 7679801; 7678782; 7542361; 9255191; 10228294; 10931436; 10655530; 17296845; 20301576; 23010537; 22322937 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hyper-IgM_syndrome_type_1 (258 variants)
- not_provided (44 variants)
- Inborn_genetic_diseases (14 variants)
- not_specified (10 variants)
- CD40LG-related_disorder (4 variants)
- Common_variable_immunodeficiency (2 variants)
- Hyperimmunoglobulin_M_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD40LG gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000074.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 39 | 12 | 52 | |||
| missense | 10 | 25 | 65 | 10 | 118 | |
| nonsense | 20 | 25 | ||||
| start loss | 0 | |||||
| frameshift | 24 | 33 | ||||
| splice donor/acceptor (+/-2bp) | 14 | 16 | ||||
| Total | 68 | 38 | 69 | 47 | 22 |
Highest pathogenic variant AF is 0.000008951029
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CD40LG | protein_coding | protein_coding | ENST00000370629 | 5 | 12198 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.721 | 0.277 | 124699 | 0 | 2 | 124701 | 0.00000802 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.30 | 61 | 97.1 | 0.628 | 0.00000715 | 1730 |
| Missense in Polyphen | 7 | 23.349 | 0.2998 | 433 | ||
| Synonymous | 1.03 | 32 | 40.3 | 0.794 | 0.00000347 | 480 |
| Loss of Function | 2.39 | 1 | 8.52 | 0.117 | 6.12e-7 | 152 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000247 | 0.0000178 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cytokine that binds to CD40/TNFRSF5 (PubMed:1280226). Costimulates T-cell proliferation and cytokine production. Its cross-linking on T-cells generates a costimulatory signal which enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation (PubMed:8617933). Induces the activation of NF-kappa-B and kinases MAPK8 and PAK2 in T- cells. Induces tyrosine phosphorylation of isoform 3 of CD28 (PubMed:15067037). Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4. Involved in immunoglobulin class switching (By similarity). {ECO:0000250|UniProtKB:P27548, ECO:0000269|PubMed:1280226, ECO:0000269|PubMed:15067037, ECO:0000269|PubMed:8617933}.;
- Disease
- DISEASE: Immunodeficiency with hyper-IgM, type 1 (HIGM1) [MIM:308230]: Immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence. {ECO:0000269|PubMed:26545377, ECO:0000269|PubMed:7532185, ECO:0000269|PubMed:7678782, ECO:0000269|PubMed:7679206, ECO:0000269|PubMed:7679801, ECO:0000269|PubMed:7717401, ECO:0000269|PubMed:8094231, ECO:0000269|PubMed:8550833, ECO:0000269|PubMed:8889581, ECO:0000269|PubMed:9150729, ECO:0000269|PubMed:9746782}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Primary immunodeficiency - Homo sapiens (human);Cell adhesion molecules (CAMs) - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Asthma - Homo sapiens (human);Malaria - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Allograft Rejection;Photodynamic therapy-induced NF-kB survival signaling;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Inflammatory Response Pathway;cd40l signaling pathway;TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;JAK STAT pathway and regulation;GPCR signaling-G alpha i;CD40/CD40L signaling;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;IL4-mediated signaling events;Calcium signaling in the CD4+ TCR pathway;Beta2 integrin cell surface interactions
(Consensus)
Recessive Scores
- pRec
- 0.761
Intolerance Scores
- loftool
- rvis_EVS
- -0.03
- rvis_percentile_EVS
- 51.4
Haploinsufficiency Scores
- pHI
- 0.610
- hipred
- Y
- hipred_score
- 0.650
- ghis
- 0.406
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.642
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cd40lg
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype;
Gene ontology
- Biological process
- inflammatory response;leukocyte cell-cell adhesion;activation of JUN kinase activity;regulation of signaling receptor activity;platelet activation;B cell differentiation;T cell costimulation;positive regulation of interleukin-10 production;positive regulation of interleukin-12 production;positive regulation of interleukin-4 production;tumor necrosis factor-mediated signaling pathway;B cell proliferation;positive regulation of T cell proliferation;negative regulation of apoptotic process;isotype switching;immunoglobulin secretion;regulation of immune response;regulation of immunoglobulin secretion;positive regulation of NF-kappaB transcription factor activity;positive regulation of endothelial cell apoptotic process
- Cellular component
- extracellular space;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface;integral component of membrane
- Molecular function
- cytokine activity;tumor necrosis factor receptor binding;CD40 receptor binding;protein binding