CD40 CD40 molecule [Homo sapiens (human)] - Gene

Summary

Official Symbol: CD40provided by HGNC
Official Full Name: CD40 moleculeprovided by HGNC
Primary source: HGNC:HGNC:11919
See related: Ensembl:ENSG00000101017 MIM:109535; AllianceGenome:HGNC:11919
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: p50; Bp50; CDW40; TNFRSF5
Summary: 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]
Expression: Broad expression in lymph node (RPKM 19.2), appendix (RPKM 13.7) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.12

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (46118314..46129858)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (47854355..47865910)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (44746953..44758497)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Frequency of CD40-1C>T polymorphism (rs1883832) and association with response to treatment in children with primary immune thrombocytopenia.
Title: Frequency of CD40-1C>T polymorphism (rs1883832) and association with response to treatment in children with primary immune thrombocytopenia.
ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer.
Title: ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer.
A call for clinical trials in glioblastoma multiforme for interleukin 4, interleukin 6, interleukin 13 and CD40.
Title: A call for clinical trials in glioblastoma multiforme for interleukin 4, interleukin 6, interleukin 13 and CD40.
CD40 is expressed in the subsets of endothelial cells undergoing partial endothelial-mesenchymal transition in tumor microenvironment.
Title: CD40 is expressed in the subsets of endothelial cells undergoing partial endothelial-mesenchymal transition in tumor microenvironment.
CD68 Antigen and Cerebral Aneurysms: A Case-Control Study.
Title: CD68 Antigen and Cerebral Aneurysms: A Case-Control Study.
A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population.
Title: A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population.
Allele-specific protein binding within the CD40 locus in human synovial fibroblasts and immune cells.
Title: Allele-specific protein binding within the CD40 locus in human synovial fibroblasts and immune cells.
Platelet factor 4 (PF4) induces cluster of differentiation 40 (CD40) expression in human aortic endothelial cells (HAECs) through the SIRT1/NF-kappaB/p65 signaling pathway.
Title: Platelet factor 4 (PF4) induces cluster of differentiation 40 (CD40) expression in human aortic endothelial cells (HAECs) through the SIRT1/NF-κB/p65 signaling pathway.
Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study.
Title: Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study.
CD40 Upregulation in the Retina of Patients With Diabetic Retinopathy: Association With TRAF2/TRAF6 Upregulation and Inflammatory Molecule Expression.
Title: CD40 Upregulation in the Retina of Patients With Diabetic Retinopathy: Association With TRAF2/TRAF6 Upregulation and Inflammatory Molecule Expression.

Submit: New GeneRIF Correction See all GeneRIFs (462)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hyper-IgM syndrome type 3 MedGen: C1720957 OMIM: 606843 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies three new risk loci for Kawasaki disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at CD40 and other loci confer risk of rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The low mannose-level gp120 induces higher activation of plasmacytoid dendritic cells by upregulation of IFN-alpha, PD-L1, CD40, CCR7, CD80, and CD86 than the high mannose-level gp120 does	PubMed
	env	Inhibition of CpG-B-induced maturation of plasmacytoid dendritic cells by HIV-1 gp120 results in downregulation of CD40, CD83, CCR7, and HLA-DR expression	PubMed
	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
	env	HIV-1 gp120-induced reduction of IL-12 parallels IL-10 induction and inhibits translocation of CD40 to the surface of monocytes	PubMed
	env	Upregulation of apoptosis genes such as NCK-associated protein 1, PTB domain adaptor protein CED-6, and TNF receptor superfamily 5 are induced by HIV-1 gp120 in human neurons	PubMed
Pr55(Gag)	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
Tat	tat	Depletion of ARMS abrogates HIV-1 Tat-induced upregulation of CD40 expression in primary human microglia	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
	tat	HIV-1 Tat upregulates the expression of MHC and co-stimulatory molecules CD40, CD80, CD83 and CD86 in monocyte-derived dendritic cells, thereby driving T cell-mediated immune responses	PubMed
Vpr	vpr	HIV-1 Vpr downregulates the expression of several immunologically important molecules including CD40, CD80, CD83, and CD86 co-stimulatory molecules on monocyte-derived macrophage (MDM) and monocyte-derived dendritic cells (MDDC)	PubMed
Vpu	vpu	HIV-1 Vpu upregulates CD40 expression, which enhances efficient expression of VCAM-1 in endothelial cells	PubMed
matrix	gag	Treatment of human PBMCs with HIV-1 MA upregulates the expression of MCP-1, ICAM-1, CD40, CD86 and CD36 and downregulates the expression of nuclear receptors FXR and PPARgamma	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93708 (e-PCR)
- UniSTS:91489

CD40_s5 (e-PCR)
- UniSTS:510346

PMC259134P3 (e-PCR)
- UniSTS:272293

STS-R49884 (e-PCR)
- UniSTS:33205

PMC60102P1 (e-PCR)
- UniSTS:273387

PMC60102P10 (e-PCR)
- UniSTS:273388

PMC60102P11 (e-PCR)
- UniSTS:273389

PMC60102P2 (e-PCR)
- UniSTS:273390

PMC60102P3 (e-PCR)
- UniSTS:273391

PMC60102P4 (e-PCR)
- UniSTS:273392

PMC60102P5 (e-PCR)
- UniSTS:273393

PMC60102P6 (e-PCR)
- UniSTS:273394

PMC60102P7 (e-PCR)
- UniSTS:273395

PMC60102P9 (e-PCR)
- UniSTS:273396

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables antigen binding	IEA Inferred from Electronic Annotation more info
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor activity	IEA Inferred from Electronic Annotation more info
enables signaling receptor activity	TAS Traceable Author Statement more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell activation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within B cell activation	IEA Inferred from Electronic Annotation more info
involved_in B cell activation	IEA Inferred from Electronic Annotation more info
involved_in B cell mediated immunity	IEA Inferred from Electronic Annotation more info
acts_upstream_of B cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in B cell proliferation	NAS Non-traceable Author Statement more info	PubMed
involved_in CD40 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in CD40 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in CD40 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to erythropoietin	IEA Inferred from Electronic Annotation more info
involved_in cellular response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within defense response to protozoan	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in immune response-regulating cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within immune response-regulating cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in immune system process	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in intracellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in intracellular calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within positive regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endothelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of interleukin-12 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-4-mediated signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of isotype switching to IgG isotypes	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein kinase C signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within regulation of immune response	IEA Inferred from Electronic Annotation more info
involved_in regulation of immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in response to cobalamin	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient levels	IEA Inferred from Electronic Annotation more info
involved_in response to peptide	IEA Inferred from Electronic Annotation more info
involved_in response to type II interferon	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of CD40 receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CD40 receptor complex	IEA Inferred from Electronic Annotation more info
part_of CD40 receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	HDA more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in varicosity	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: tumor necrosis factor receptor superfamily member 5

Names: B cell surface antigen CD40; B cell-associated molecule; CD40 molecule, TNF receptor superfamily member 5; CD40L receptor

NCBI Reference Sequences (RefSeq)

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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

NG_007279.1 RefSeqGene

Range

4988..16479

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_40

mRNA and Protein(s)

NM_001250.6 → NP_001241.1 tumor necrosis factor receptor superfamily member 5 isoform 1 precursor

See identical proteins and their annotated locations for NP_001241.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AL035662, BC012419, BC064518, BM761221, BX364284

Consensus CDS

CCDS13393.1

UniProtKB/Swiss-Prot

E1P5S9, P25942, Q53GN5, Q5JY15, Q5U007, Q7M4Q8, Q86YK5, Q9BYU0

UniProtKB/TrEMBL

A0A0S2Z3C7

Related

ENSP00000361359.3, ENST00000372285.8

Conserved Domains (1) summary

cd13407
Location:26 → 186

TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
NM_001302753.2 → NP_001289682.1 tumor necrosis factor receptor superfamily member 5 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL035662, BC012419, BC064518, BM761221, BX364284, BX364285

Consensus CDS

CCDS93053.1

UniProtKB/TrEMBL

A0A8Q3SI60

Related

ENSP00000512093.1, ENST00000695671.1

Conserved Domains (1) summary

cd13407
Location:26 → 186

TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
NM_001322421.2 → NP_001309350.1 tumor necrosis factor receptor superfamily member 5 isoform 4 precursor

Status: REVIEWED

Source sequence(s)

AL035662, BX364284, HY063089

Conserved Domains (1) summary

cd13407
Location:26 → 186

TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
NM_001322422.2 → NP_001309351.1 tumor necrosis factor receptor superfamily member 5 isoform 5 precursor

Status: REVIEWED

Source sequence(s)

AK222896, AL035662, BX364284, HY063089

UniProtKB/TrEMBL

A0A0S2Z349

Conserved Domains (2) summary

cd00185
Location:62 → 103

TNFRSF; CRD2 [structural motif]

cl22855
Location:26 → 135

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
NM_001362758.2 → NP_001349687.1 tumor necrosis factor receptor superfamily member 5 isoform 6 precursor

Status: REVIEWED

Source sequence(s)

AL035662

UniProtKB/TrEMBL

A0A8Q3WKP3

Related

ENSP00000512096.1, ENST00000489304.6

Conserved Domains (1) summary

cd13407
Location:26 → 186

TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40
NM_001424339.1 → NP_001411268.1 tumor necrosis factor receptor superfamily member 5 isoform 7 precursor

Status: REVIEWED

Source sequence(s)

AL035662
NM_152854.4 → NP_690593.1 tumor necrosis factor receptor superfamily member 5 isoform 2 precursor

See identical proteins and their annotated locations for NP_690593.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The resulting isoform (2) contains a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL035662, BC012419, BC064518, BM761221, BX364284

Consensus CDS

CCDS13394.1

UniProtKB/TrEMBL

A0A8Q3WKP3

Related

ENSP00000361350.3, ENST00000372276.7

Conserved Domains (1) summary

cd13407
Location:26 → 166

TNFRSF5; Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40

RNA

NR_126502.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two internal exons and uses an alternate splice site in the 3' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK222896, AL035662, BC012419, BC064518, BX364284

Related

ENST00000620709.4
NR_136327.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL035662, BX364284, HY063089

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000020.11 Reference GRCh38.p14 Primary Assembly

Range

46118314..46129858

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017028135.2 → XP_016883624.1 tumor necrosis factor receptor superfamily member 5 isoform X1
XM_017028136.2 → XP_016883625.1 tumor necrosis factor receptor superfamily member 5 isoform X2
XM_011529109.3 → XP_011527411.1 tumor necrosis factor receptor superfamily member 5 isoform X5

See identical proteins and their annotated locations for XP_011527411.1

UniProtKB/TrEMBL

H0YE23

Related

ENSP00000434825.1, ENST00000466205.5

Conserved Domains (2) summary

cd00185
Location:62 → 103

TNFRSF; CRD2 [structural motif]

cl22855
Location:26 → 135

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
XM_047440601.1 → XP_047296557.1 tumor necrosis factor receptor superfamily member 5 isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060944.1 Alternate T2T-CHM13v2.0

Range

47854355..47865910

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054324242.1 → XP_054180217.1 tumor necrosis factor receptor superfamily member 5 isoform X1
XM_054324243.1 → XP_054180218.1 tumor necrosis factor receptor superfamily member 5 isoform X2
XM_054324246.1 → XP_054180221.1 tumor necrosis factor receptor superfamily member 5 isoform X5

UniProtKB/TrEMBL

H0YE23
XM_054324245.1 → XP_054180220.1 tumor necrosis factor receptor superfamily member 5 isoform X4