CD40

CD40 molecule, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 20:46118271-46129863

Previous symbols: [ "TNFRSF5" ]

Links

ENSG00000101017 ∙ NCBI:958 ∙ OMIM:109535 ∙ HGNC:11919 ∙ Uniprot:P25942 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyper-IgM syndrome type 3 (Moderate), mode of inheritance: AR
• hyper-IgM syndrome type 3 (Strong), mode of inheritance: AR
• hyper-IgM syndrome type 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency with Hyper-IgM, type 3	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported	Allergy/Immunology/Infectious	11675497; 12915844; 12584544; 17502893; 20301576

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD40 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD40 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	63	2	66
missense			48	5	3	56
nonsense	2					2
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		2			1	3
splice region			8	12	2	22
non coding			15	58	16	89
Total	2	2	65	126	22

Highest pathogenic variant AF is 0.00000657

Variants in CD40

This is a list of pathogenic ClinVar variants found in the CD40 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-46118274-CT-C		Hyperimmunoglobulin M syndrome	Benign/Likely benign (Aug 17, 2016)
20-46118277-G-T		Hyper-IgM syndrome type 3	Uncertain significance (Feb 02, 2018)
20-46118283-G-T		Hyper-IgM syndrome type 3	Uncertain significance (Jan 13, 2018)
20-46118289-C-G		Hyper-IgM syndrome type 3	Uncertain significance (Jan 13, 2018)
20-46118303-C-T		Hyper-IgM syndrome type 3	Benign (May 14, 2021)
20-46118343-T-C		not specified • Hyper-IgM syndrome type 3	Benign (Jan 24, 2024)
20-46118343-TA-T			Uncertain significance (Apr 16, 2022)
20-46118352-T-C			Likely benign (Dec 01, 2023)
20-46118355-G-T			Likely benign (Nov 13, 2023)
20-46118365-T-G			Uncertain significance (Sep 27, 2022)
20-46118367-C-T			Likely benign (Jan 27, 2024)
20-46118370-C-G			Likely benign (Jun 07, 2023)
20-46118376-G-A			Pathogenic (Jul 21, 2023)
20-46118388-G-A			Likely benign (Jul 03, 2023)
20-46118391-C-T			Likely benign (Jan 08, 2024)
20-46118392-G-T			Uncertain significance (Dec 24, 2021)
20-46118401-T-C		not specified	Uncertain significance (Oct 06, 2022)
20-46118409-C-T			Likely benign (Mar 21, 2023)
20-46118410-C-T			Likely benign (Nov 07, 2023)
20-46118411-C-T			Likely benign (Dec 12, 2023)
20-46118413-G-A			Likely benign (Dec 30, 2022)
20-46118414-A-G			Likely benign (Dec 31, 2022)
20-46118447-G-A		not specified	Benign (Jan 24, 2024)
20-46118465-C-T			Benign (May 11, 2021)
20-46121801-T-C			Likely benign (Mar 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD40	protein_coding	protein_coding	ENST00000372285	9	11592

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.846	0.154	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	104	153	0.680	0.00000850	1807
Missense in Polyphen		17	46.428	0.36616		539
Synonymous	-0.610	66	60.0	1.10	0.00000374	517
Loss of Function	3.10	2	14.9	0.134	6.51e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion.
• Pathway: Primary immunodeficiency - Homo sapiens (human);Cell adhesion molecules (CAMs) - 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);HTLV-I infection - Homo sapiens (human);Malaria - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Transcriptional misregulation in cancer - 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);Epstein-Barr virus infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Allograft Rejection;Human Complement System;Vitamin D Receptor Pathway;NLR Proteins;Inflammatory Response Pathway;Toll-like Receptor Signaling 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;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;IL4;IL6;CD40/CD40L signaling (Consensus)

Recessive Scores

• pRec: 0.728

Intolerance Scores

• loftool: 0.148
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.27

Haploinsufficiency Scores

• pHI: 0.169
• hipred: Y
• hipred_score: 0.546
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.712

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cd40
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system 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); hematopoietic system phenotype; normal phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: positive regulation of protein phosphorylation;immune response-regulating cell surface receptor signaling pathway;cellular calcium ion homeostasis;inflammatory response;platelet activation;positive regulation of B cell proliferation;positive regulation of interleukin-12 production;tumor necrosis factor-mediated signaling pathway;response to cobalamin;response to interferon-gamma;cellular response to erythropoietin;B cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;defense response to protozoan;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of MAP kinase activity;protein kinase B signaling;positive regulation of blood vessel endothelial cell migration;positive regulation of GTPase activity;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;positive regulation of isotype switching to IgG isotypes;regulation of immune response;regulation of immunoglobulin secretion;positive regulation of NF-kappaB transcription factor activity;defense response to virus;protein-containing complex assembly;cellular response to lipopolysaccharide;cellular response to mechanical stimulus;cellular response to interleukin-1;positive regulation of protein kinase C signaling;response to peptide;positive regulation of endothelial cell apoptotic process
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface;CD40 receptor complex;neuronal cell body;varicosity;intracellular membrane-bounded organelle;extracellular exosome
• Molecular function: antigen binding;protein binding;enzyme binding;protein domain specific binding;ubiquitin protein ligase binding;signaling receptor activity