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CD40 Gene

protein-coding GIFtS: 70
GCID: GC20P044746

CD40 Molecule, TNF Receptor Superfamily Member 5

(Previous names: tumor necrosis factor receptor superfamily, member 5)
(Previous symbol: TNFRSF5)

See CD40-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
CD40 Molecule, TNF Receptor Superfamily Member 5¹ ²		B Cell-Associated Molecule²
TNFRSF5¹ ² ³ ⁵		CD40 Antigen (TNF Receptor Superfamily Member 5)²
Tumor Necrosis Factor Receptor Superfamily, Member 5¹ ²		CD40 Type II Isoform²
Bp50² ³		Nerve Growth Factor Receptor-Related B-Lymphocyte Activation Molecule²
B-Cell Surface Antigen CD40² ³		p50²
CD40L Receptor² ³		Tumor Necrosis Factor Receptor Superfamily Member 5²
CDW40²		CDw40³
B Cell Surface Antigen CD40²		CD40 Antigen³

External Ids:	HGNC: 11919¹	Entrez Gene: 958²	Ensembl: ENSG00000101017⁷	OMIM: 109535⁵	UniProtKB: P25942³

ORGUL members:

Export aliases for CD40 gene to outside databases

Previous GC identifers: GC20P044181 GC20P041488

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CD40 Gene:

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been found to be

essential in 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. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been

reported. (provided by RefSeq, Jul 2008)

GeneCards Summary for CD40 Gene:

CD40 (CD40 molecule, TNF receptor superfamily member 5) is a protein-coding gene. Diseases associated with CD40 include chromosome 20q deletion, and cd40 deficiency. GO annotations related to this gene include receptor activity and signal transducer activity. An important paralog of this gene is TNFRSF21.

UniProtKB/Swiss-Prot: TNR5_HUMAN, P25942

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

Gene Wiki entry for CD40 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000020.10 NT_011362.11 NC_018931.2

Regulatory elements:

Regulatory transcription factor binding sites in the CD40 gene promoter:
c-Fos AP-1 ATF-2 c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CD40 promoter sequence

Search Chromatin IP Primers for CD40

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CD40

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q12-q13.2 Ensembl cytogenetic band: 20q13.12 HGNC cytogenetic band: 20q12-q13.2

CD40 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CD40 gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20P044746: view genomic region (about GC identifiers)

Start:	44,746,906 bp from pter	End:	44,758,502 bp from pter
Size:	11,597 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: TNR5_HUMAN, P25942 (See protein sequence)

Recommended Name: Tumor necrosis factor receptor superfamily member 5 precursor

Size: 277 amino acids; 30619 Da

Subunit: 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

6 PDB 3D structures from and Proteopedia for CD40:

1CDF (3D)

1CZZ (3D)

1D00 (3D)

1FLL (3D)

1LB6 (3D)

3QD6 (3D)

Secondary accessions: E1P5S9 Q53GN5 Q5JY15 Q5U007 Q7M4Q8 Q86YK5 Q9BYU0

Alternative splicing: 2 isoforms: P25942-1 P25942-2

Explore the universe of human proteins at neXtProt for CD40: NX_P25942

Explore proteomics data for CD40 at MOPED

Post-translational modifications:

Glycosylation² at Asn153, Asn180

Modification sites at PhosphoSitePlus

See CD40 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (2 alternative transcripts):

NP_001241.1 NP_690593.1

ENSEMBL proteins:

ENSP00000361359 ENSP00000361350 ENSP00000434825

Reactome Protein details: P25942

CD40 Human Recombinant Protein Products:

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	R&D Systems Recombinant & Natural Proteins for CD40 (CD40/TNFRSF5)
	Enzo Life Sciences proteins for CD40
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate for CD40 OriGene Custom MassSpec OriGene Custom Protein Services for CD40
	GenScript Purified and Recombinant Proteins for CD40
	Novus Biologicals CD40 Proteins Novus Biologicals CD40 Lysates
	Sino Biological Recombinant Protein for CD40 Sino Biological Cell Lysate for CD40
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Cloud-Clone Corp.
	Search eBioscience for Proteins for CD40
	antibodies-online proteins for CD40 (25 products)
	antibodies-online peptides for CD40

CD40 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	R&D Systems Antibodies for CD40 (CD40/TNFRSF5)
	OriGene Antibodies for CD40 OriGene Custom Antibody Services for CD40
	Novus Biologicals CD40 Antibodies
	Abcam antibodies for CD40
	Browse Antibodies at Cloud-Clone Corp.
	ThermoFisher Antibodies for CD40
	antibodies-online antibodies for CD40 (452 products)

CD40 Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for CD40
	R&D Systems ELISAs for CD40 (CD40/TNFRSF5) (see all)
	GenScript Custom Assay Services for CD40
	Enzo Life Sciences assays for CD40
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.
	eBioscience ELISAs for CD40: Human sCD40 Platinum ELISA 10 x 96 tests
	antibodies-online kits for CD40 (41 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

CD: CD molecules

TNFRSF: Tumor necrosis factor receptor superfamily

IUPHAR Guide to PHARMACOLOGY protein family classification: CD40

Tumour necrosis factor (TNF) receptor family

2 InterPro protein domains:

IPR020435 TNFR_5

IPR001368 TNFR/NGFR_Cys_rich_reg

Graphical View of Domain Structure for InterPro Entry P25942

ProtoNet protein and cluster: P25942

2 Blocks protein domains:

IPB001368 TNFR/CD27/30/40/95 cysteine-rich region

IPB008063 FAS/CD95 receptor family signature

UniProtKB/Swiss-Prot: TNR5_HUMAN, P25942

Similarity: Contains 4 TNFR-Cys repeats

Find genes that share domains with CD40 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: TNR5_HUMAN, P25942

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

Gene Ontology (GO): Selected molecular function terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003823	antigen binding	IEA	--
GO:0004871	signal transducer activity	TAS	9671306
GO:0004872	receptor activity	TAS	10092834
GO:0005515	protein binding	IPI	12140561
GO:0019899	enzyme binding	IPI	12223522

Find genes that share ontologies with CD40 About GenesLikeMe

Phenotypes:
7 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Cd40):

hematopoietic system	homeostasis/metabolism	immune system	nervous system	normal
renal/urinary system	skeleton

Find genes that share phenotypes with CD40 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for CD40: Cd40^tm1Geha Cd40^tm1Kik Cd40^tm1Arah

genOway: Develop your customized and physiologically relevant rodent model for CD40

miRNA Products:		miRTarBase miRNAs that target CD40: hsa-mir-486-5p (MIRT004620), hsa-mir-224-5p (MIRT003393)

		Block miRNA regulation of human, mouse, rat CD40 using miScript Target Protectors
		8 qRT-PCR Assays for microRNAs that regulate CD40:
		hsa-miR-30c-2* hsa-miR-30c-1* hsa-miR-575 hsa-miR-145 hsa-miR-3165 hsa-miR-3155 hsa-miR-3155b hsa-miR-484

		SwitchGear 3'UTR luciferase reporter plasmid: CD40 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for CD40
		Predesigned siRNA for gene silencing in human, mouse, rat CD40

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for CD40

Clone Products:		OriGene clones in human, mouse for CD40 (see all 14) OriGene ORF clones in mouse, rat for CD40 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): CD40 (NM_152854)
		Sino Biological Human cDNA Clone for CD40
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CD40
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CD40
		Addgene plasmids for CD40

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for CD40
		Browse ESI BIO Cell Lines and PureStem Progenitors for CD40

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CD40

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

TNR5_HUMAN, P25942: Isoform I: Cell membrane; Single-pass type I membrane protein

TNR5_HUMAN, P25942: Isoform II: Secreted

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
extracellular	5
plasma membrane	5
nucleus	3
endosome	2
lysosome	2
vacuole	2
cytoskeleton	1
cytosol	1
mitochondrion	1
peroxisome	1

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Gene Ontology (GO): Selected cellular component terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	--	--
GO:0005615	extracellular space	IEA	--
GO:0005737	cytoplasm	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	TAS	10748139

Find genes that share ontologies with CD40 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for CD40 About (see all 21)

See pathways by source

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SuperPath

Contained pathways About

Allograft rejection

Allograft rejection	0.86	Asthma	0.46
Allograft Rejection	0.86	Intestinal immune network for IgA production	0.41
Autoimmune thyroid disease	0.61	Viral myocarditis	0.40

TNF Signaling

	TNF Signaling	0.50			TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions	0.49
	Death Receptor Signaling	0.50			NF-kB (NFkB) Pathway	0.46

Toll-like receptor signaling pathway

	Toll-like receptor signaling pathway	0.94			Regulation of toll-like receptor signaling pathway	0.93
	Toll-like receptor signaling pathway	0.94

Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway

Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway

0.46

PEDF Induced Signaling

Cytokine-cytokine receptor interaction

0.43

Find genes that share SuperPaths with CD40 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

2 R&D Systems Pathways for CD40

	TNF Superfamily - Human Ligand-Receptor Interactions & their Associated Functions
	A-beta Uptake & Degradation

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CD40 (see all 15)

	THC Differentiation Pathway
	STAT3 Pathway
	TRAF Pathway
	Molecular Mechanisms of Cancer
	Antioxidant Action of Vitamin-C

1 GeneGo (Thomson Reuters) Pathway for CD40

Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway

Selected BioSystems Pathways for CD40 (see all 7)

	NLR proteins
	Allograft Rejection
	Toll-like receptor signaling pathway
	IL-6 Signaling Pathway
	CD40/CD40L signaling

3 Sino Biological Pathways for CD40

	TNF Signaling
	Death Receptor Signaling
	NF-kB (NFkB) Pathway

1 Reactome Pathway for CD40

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Selected Kegg Pathways (Kegg details for CD40) (see all 16):

	Cytokine-cytokine receptor interaction
	NF-kappa B signaling pathway
	Cell adhesion molecules (CAMs)
	Toll-like receptor signaling pathway
	Intestinal immune network for IgA production

Pathway & Disease-focused RT² Profiler PCR Arrays including CD40 (see all 21):

Cell Surface Markers in human mouse rat

Antiviral Response in human mouse rat

Multiple Sclerosis in human mouse rat

Lymphoma in human mouse rat

T-cell & B-cell Activation in human mouse rat

Interactions:

GeneGlobe Interaction Network for CD40

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for CD40 (P25942^{1, 3} ENSP00000361359⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 91)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
TRAF6	Q9Y4K3¹^,³	EBI-525714,EBI-359276 I2D: score=7
ENSG00000229802	Q92504³, ENSP00000391735⁴	I2D: score=2 STRING: ENSP00000391735
SLC39A7	Q92504³, ENSP00000363807⁴	I2D: score=2 STRING: ENSP00000363807
ENSG00000206288	Q92504³	I2D: score=2
ENSG00000224399	Q92504³	I2D: score=2

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Gene Ontology (GO): Selected biological process terms (see all 25): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001934	positive regulation of protein phosphorylation	IMP	--
GO:0002768	immune response-regulating cell surface receptor signaling pathway	IEA	--
GO:0006461	protein complex assembly	TAS	10748139
GO:0006874	cellular calcium ion homeostasis	IMP	--
GO:0006954	inflammatory response	IEA	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for CD40 (TNR5)

1 HMDB Compound for CD40 About this table

Compound	Synonyms	CAS #	PubMed Ids
Simvastatin	(+)-Simvastatin (see all 28)	79902-63-9	--

1 IUPHAR Ligand for CD40 (CD40) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
CD40 ligand	None	None		--

Selected Novoseek inferred chemical compound relationships for CD40 gene (see all 116) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
lfa703	69.8	4	15618295 (3), 17482516 (1)
rantes	59.7	36	16864989 (8), 11274230 (5), 12122011 (3), 11754818 (1) (see all 18)
blys	55.5	12	19421221 (3), 17567982 (2), 11015437 (1), 12154359 (1) (see all 6)
ionomycin	48.9	9	1708162 (1), 16223731 (1), 9727564 (1), 7699321 (1) (see all 9)
pdtc	47.1	3	20037166 (1), 12901869 (1), 16141529 (1)
triazolopyrimidine	43.2	7	10600333 (5)
sb 203580	43	5	16356505 (1), 11708812 (1), 12209089 (1), 17911635 (1)
n-tosyl-l-phenylalanine chloromethyl ketone	37	1	10995749 (1)
pd 98,059	36	5	16272352 (1), 16904975 (1), 19288477 (1), 10586056 (1)
ly294002	35.9	2	15888255 (1), 18174238 (1)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for CD40 gene (2 alternative transcripts):

NM_001250.4 NM_152854.2

Unigene Cluster for CD40:

CD40 molecule, TNF receptor superfamily member 5

Hs.472860 [show with all ESTs]

Unigene Representative Sequence: AB209660

6 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000372285(uc002xrf.1 uc002xrg.1 uc002xrh.1 uc002xrj.1 uc002xrk.1)

ENST00000372276 ENST00000466205 ENST00000489304 ENST00000477696 ENST00000461171

miRNA Products:		Block miRNA regulation of human, mouse, rat CD40 using miScript Target Protectors
		8 qRT-PCR Assays for microRNAs that regulate CD40:
		hsa-miR-30c-2* hsa-miR-30c-1* hsa-miR-575 hsa-miR-145 hsa-miR-3165 hsa-miR-3155 hsa-miR-3155b hsa-miR-484

		SwitchGear 3'UTR luciferase reporter plasmid: CD40 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for CD40
		Predesigned siRNA for gene silencing in human, mouse, rat CD40

Clone Products:		OriGene clones in human, mouse for CD40 (see all 14) OriGene ORF clones in mouse, rat for CD40 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): CD40 (NM_152854)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CD40
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CD40
		Addgene plasmids for CD40

Primer Products:		OriGene qPCR primer pairs and template standards for CD40 OriGene qSTAR qPCR primer pairs in human, mouse for CD40
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat CD40
		QuantiTect SYBR Green Assays in human, mouse, rat CD40
		QuantiFast Probe-based Assays in human, mouse, rat CD40

Additional mRNA sequence:

AB209660.1 AJ300189.1 AK222896.1 AY225405.1 BC012419.1 BC064518.1 BT019901.1

9 DOTS entries:

DT.451574 DT.100791759 DT.86853137 DT.100791764 DT.92423397 DT.102104 DT.95170181 DT.40204598

DT.95170183

Selected AceView cDNA sequences (see all 119):

BM456032 AI620202 AA934395 BM708033 AA749024 AA876065 AY225405 AA913214

AI791563 AI733071 BI759406 H50599 BQ548631 AA806068 AI356484 CK826276

BM707407 NM_001250 CA944736 AA767182 AA886208 CA305932 CR608994 NM_152854

GeneLoc Exon Structure

4 Alternative Splicing Database (ASD) splice patterns (SP) for CD40 About this scheme

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

ECgene alternative splicing isoforms for CD40

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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CD40 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: --

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CD40 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 7) fully expand


Blood (Hematopoietic System) fully expand to see all 9 entries
Monocytes Peripheral Blood
Immunosuppressive dendritic cells

Fibroblasts
Dermal Fibroblasts Dorsal Dermis

Dermis (Integumentary System) fully expand to see all 3 entries
Dermal Fibroblasts Dorsal Dermis

Bone (Muscoskeletal System) fully expand to see all 3 entries
Zeugopod Periosteum
Bone marrow-derived mesenchymal stem cells

Heart (Cardiovascular System)
Atrioventricular Canal Cells Atrioventricular Canal

CD40 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

CD40 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.472860

UniProtKB/Swiss-Prot: TNR5_HUMAN, P25942

Tissue specificity: B-cells and in primary carcinomas

Pathway & Disease-focused RT² Profiler PCR Arrays including CD40 (see all 21):

Cell Surface Markers in human mouse rat

Antiviral Response in human mouse rat

Multiple Sclerosis in human mouse rat

Lymphoma in human mouse rat

T-cell & B-cell Activation in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for CD40 OriGene qSTAR qPCR primer pairs in human, mouse for CD40
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat CD40
		QuantiTect SYBR Green Assays in human, mouse, rat CD40
		QuantiFast Probe-based Assays in human, mouse, rat CD40

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CD40

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for CD40 gene from Selected species (see all 10) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Cd40^{1 , 5}	CD40 antigen^{1, 5}	71.29(n)¹ 62.77(a)¹		2 (85.38 cM)⁵ 21939¹ NM_011611.2¹ NP_035741.2¹ 165055627⁵
chicken (Gallus gallus)	Aves	CD40¹	CD40 molecule, TNF receptor superfamily member 5	52.58(n) 42.64(a)		395385 NM_204665.2 NP_989996.1
lizard (Anolis carolinensis)	Reptilia	CD40⁶	CD40 molecule, TNF receptor superfamily member 5	37(a)	1 ↔ 1	GL343871.1(80493-94195)
tropical clawed frog (Xenopus tropicalis)	Amphibia	cd40¹	CD40 molecule, TNF receptor superfamily member 5	47.77(n) 39.46(a)		100270675 NM_001145216.1 NP_001138688.1
zebrafish (Danio rerio)	Actinopterygii	cd40⁶	CD40 antigen	25(a)	many ↔ many	23(37916785-37929019) ENSDARG00000054968

ENSEMBL Gene Tree for CD40 (if available)
TreeFam Gene Tree for CD40 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for CD40 gene

TNFRSF21² TNFRSF11A² TNFRSF6B² LTBR² TNFRSF11B² TNFRSF14² TNFRSF1B²

3 SIMAP similar genes for CD40 using alignment to 3 protein entries: TNR5_HUMAN (see all proteins):

TNFRSF11A TNFRSF1B TNFR1B

Find genes that share paralogs with CD40 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 20 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28931586^1,2,,4	C	Immunodeficiency with hyper-IgM 3 (HIGM3)⁴ pathogenic¹	44721508(+)	`AATACC/TGCGAC`	4	R C	mis¹ ese³		0	--	--	--	--
VAR_039302⁴		Bladder carcinoma cell line Hu549⁴	--	see VAR_039302	2	S G	mis⁴		0	--	--	--	--
VAR_039301⁴		Bladder carcinoma cell line Hu549⁴	--	see VAR_039301	2	C Q	mis⁴		0	--	--	--	--
VAR_039303⁴		Bladder carcinoma cell line Hu549⁴	--	see VAR_039303	2	S T	mis⁴		0	--	--	--	--
rs117155325^1,2	F	--	44715482(+)	`GTGAGG/ATCTGG`	2	--	us2k¹		1		NA	120
rs146463701^1,2		--	44715658(+)	`GAGTGC/TTAACA`	2	--	us2k¹		0	--	--	--	--
rs184137874^1,2		--	44715916(+)	`GAGCCG/TAGATC`	2	--	us2k¹		0	--	--	--	--
rs114809260^1,2	F	--	44715976(+)	`AACCCA/CAAAAC`	2	--	us2k¹		1		WA	118
rs189900939^1,2		--	44716005(+)	`CCAAAA/GAACAA`	2	--	us2k¹		0	--	--	--	--
rs73115005^1,2	C,F	--	44716413(+)	`CTCAAG/CCAATC`	2	--	us2k¹		1		WA	118

HapMap Linkage Disequilibrium report for CD40 (44746906 - 44758502 bp)

Structural Variations
Database of Genomic Variants (DGV) 2 variations for CD40: About this table

Variant ID	Type	Subtype	PubMed ID
nsv833993	CNV	Gain	17160897
dgv1329e1	CNV	Complex	17122850

Human Gene Mutation Database (HGMD): CD40
Locus Specific Mutation Databases (LSDB): CD40

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing CD40

DNA2.0 Custom Variant and Variant Library Synthesis for CD40

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 109535
OMIM disorders: 606843
UniProtKB/Swiss-Prot: TNR5_HUMAN, P25942

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. Note=The disease is caused by mutations affecting the gene represented in this entry

Selected diseases for CD40 (see all 21):
About MalaCards

chromosome 20q deletion cd40 deficiency blood protein disease x-linked hyper igm syndrome

plasma cell leukemia frozen shoulder monocytic leukemia cervical squamous cell carcinoma

autoimmune thrombocytopenic purpura graves' disease alzheimer's disease primary immunodeficiency disease

biotin deficiency macroglobulinemia acute monocytic leukemia limb ischemia

critical limb ischemia waldenstrom macroglobulinemia plasmodium vivax malaria chronic lymphocytic leukemia

12 inferred disease relationships from the University of Copenhagen DISEASES database for CD40:

Lymphoma Hypersensitivity reaction type II disease Primary immunodeficiency disease Leukemia

Atherosclerosis Connective tissue disease Multiple sclerosis Multiple myeloma

Blood protein disease Rheumatoid arthritis Tetanus Hyperthyroidism

Find genes that share disorders with CD40 About GenesLikeMe

Selected Novoseek inferred disease relationships for CD40 gene (see all 93) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hyper-igm syndrome	80.7	23	9058789 (3), 14752331 (2), 11358428 (2), 10559240 (1) (see all 14)
higm3	77.3	3	15661021 (1), 14610488 (1), 12893749 (1)
necrosis	74.5	256	9511754 (3), 14517219 (2), 10096561 (2), 10318845 (2) (see all 99)
tumors	61.1	374	8623911 (6), 11304696 (6), 10980464 (5), 10473114 (4) (see all 99)
m syndrome	59	2	15661021 (1), 8914765 (1)
inflammation	56.9	68	11488834 (2), 19183933 (2), 12209092 (2), 19834879 (2) (see all 52)
autoimmune diseases	49.4	15	9617563 (1), 17114447 (1), 12223069 (1), 19421221 (1) (see all 12)
atherosclerosis	48	21	17967972 (2), 15921025 (1), 16904975 (1), 19896127 (1) (see all 19)
lymphocytic leukemia chronic b-cell	44.7	7	1281692 (2), 11313271 (1), 11426465 (1), 9531577 (1) (see all 6)
lymphoma	43.3	52	7530508 (3), 7541711 (3), 11825564 (3), 9137085 (2) (see all 30)

Genetic Association Database (GAD): CD40
Human Genome Epidemiology (HuGE) Navigator: CD40 (89 documents)

Export disorders for CD40 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for CD40 gene, integrated from 10 sources (see all 1602):
(articles sorted by number of sources associating them with CD40)

Utopia: connect your pdf to the dynamic
world of online information

CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization. (PubMed id 9718306)^{1, 2, 9} Pullen S.S....Kehry M.R. (Biochemistry 1998)
Association analysis of CD40 polymorphisms with asthma and the level of serum total IgE. (PubMed id 17255560)^{1, 4, 9} Park J.H....Shin H.D. (Am. J. Respir. Crit. Care Med. 2007)
Allelic variants of CD40 and CD40L genes interact to promote antibiotic-induced cutaneous allergic reactions. (PubMed id 19735272)^{1, 4, 9} Kim S.H....Park H.W. (Clin. Exp. Allergy 2009)
Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus. (PubMed id 19421221)^{1, 4, 9} Malheiros D. and Petzl-Erler M.L. (Genes Immun. 2009)
Downstream regulator TANK binds to the CD40 recognition site on TRAF3. (PubMed id 12005438)^{1, 2, 9} Li C.... Ely K.R. (Structure 2002)
Determination of carbohydrate structures N-linked to soluble CD154 and characterization of the interactions of CD40 with CD154 expressed in Pichia pastoris and Chinese hamster ovary cells. (PubMed id 11676606)^{1, 2, 9} Khandekar S.S....Fishman-Lobell J. (Protein Expr. Purif. 2001)
Molecular basis for CD40 signaling mediated by TRAF3. (PubMed id 10984535)^{1, 2, 9} Ni C.Z.... Ely K.R. (Proc. Natl. Acad. Sci. U.S.A. 2000)
The role of polar interactions in the molecular recognition of CD40L with its receptor CD40. (PubMed id 9605317)^{1, 2, 9} Singh J.... Thomas D. (Protein Sci. 1998)
Association of CD40 gene polymorphism (C-1T) with susceptibility and phenotype of Graves' disease. (PubMed id 16279844)^{1, 4, 9} Kurylowicz A....Bednarczuk T. (Thyroid 2005)
Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5). (PubMed id 9511754)^{1, 2, 9} Mizushima S.... Inoue J. (Gene 1998)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 958	HGNC: 11919	AceView: TNFRSF5	Ensembl:ENSG00000101017	euGenes: HUgn958
ECgene: CD40	Kegg: 958	H-InvDB: CD40

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for CD40	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for CD40	Genetics and Cytogenetics in Oncology and Haematology
CD40base	http://bioinf.uta.fi/CD40base/
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=CD40[genesymbol]
NIEHS-SNPs	http://egp.gs.washington.edu/data/tnfrsf5/
Wikipedia	http://en.wikipedia.org/wiki/CD40

Intellectual Property for CD40 gene
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Patent Information for CD40 gene:
Search GeneIP for patents involving CD40

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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CD40 Gene

CD40 Molecule, TNF Receptor Superfamily Member 5

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latent infection
Leukemia B-Cell
Leukemia T-Cell
HYPER-IgM SYNDROME
IMMUNE DISORDER
Herpes Simplex
Acute myocardial infarction
Waldenstrom Macroglobulinemia
Dermatitis Atopic
Lymphoma T-Cell
Cystic Fibrosis
Hypersensitivity Contact
LUNG CARCINOMA
Lymphoma Follicular
Atherosclerosis
Ischemia
Skin Diseases
Liver diseases
Breast Cancer
HIGM3
AIDS
M SYNDROME
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Hepatitis B Chronic
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Multiple Sclerosis
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carcinoma transitional cell bladder
cervical squamous cell carcinoma
Monocytic leukemia
Leukemia Hairy Cell
immunodeficiency
Psoriasis
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Cervical Cancer
MYELOMA
Rheumatoid Arthritis
Pneumonia
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Metastasis
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atherosclerotic plaque
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Heart Failure Congestive
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LANGERHANS CELL HISTIOCYTOSIS
Sjogrens Syndrome
Calcification
Arteriosclerosis
Carcinoma Renal Cell
Cancer Lung
Inflammatory Bowel Diseases
HEART FAILURE
Acute monocytic leukemia
Lymphoma B-Cell
Heart Diseases
Insulin Resistance
MALT Lymphoma
Immunological Diseases
OVARIAN CARCINOMA
Lymphoproliferative Disorders
Lymphocytic Leukemia Chronic B-Cell
autoimmune thyroid disease
SKIN LESION
STROKE
Graves Disease
Lupus Nephritis
EBV Infections
chronic liver disease
Lymphoma Non-Hodgkins
Hashimotos Thyroiditis
Plasmacytoma
Polymyositis
LEUKAEMIA LYMPHOCYTIC
Lupus Erythematosus Systemic

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CD40 Gene

CD40 Molecule, TNF Receptor Superfamily Member 5

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