TNFRSF21 TNF receptor superfamily member 21 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNFRSF21provided by HGNC
Official Full Name: TNF receptor superfamily member 21provided by HGNC
Primary source: HGNC:HGNC:13469
See related: Ensembl:ENSG00000146072 MIM:605732; AllianceGenome:HGNC:13469
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: DR6; CD358; BM-018
Summary: This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013]
Expression: Broad expression in urinary bladder (RPKM 50.6), fat (RPKM 36.4) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p12.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (47231532..47309905, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (47068690..47147063, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (47199268..47277641, complement)

Chromosome 6 - NC_000006.12 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.
Title: Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.
Long Noncoding RNAs Testis Development Related Gene 1 Aggravates Transforming Growth Factor-beta1-Induced Fibrogenesis and Inflammatory Response of Cardiac Fibroblasts Via miR-605-3p/Tumor Necrosis Factor Receptor Superfamily-21 Axis.
Title: Long Noncoding RNAs Testis Development Related Gene 1 Aggravates Transforming Growth Factor-β1-Induced Fibrogenesis and Inflammatory Response of Cardiac Fibroblasts Via miR-605-3p/Tumor Necrosis Factor Receptor Superfamily-21 Axis.
Death Receptor 6 as a Prognostic Marker in Low-grade Glioma.
Title: Death Receptor 6 as a Prognostic Marker in Low-grade Glioma.
Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates Death Receptor 6 Induced Apoptosis.
Title: Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates Death Receptor 6 Induced Apoptosis.
circTNFRSF21, a newly identified circular RNA promotes endometrial carcinoma pathogenesis through regulating miR-1227-MAPK13/ATF2 axis.
Title: circTNFRSF21, a newly identified circular RNA promotes endometrial carcinoma pathogenesis through regulating miR-1227-MAPK13/ATF2 axis.
Variants in TNFRSF21 cause non-syndromic high myopia in Chinese population.
Title: TNFRSF21 mutations cause high myopia.
Hepatitis C virus modulates DR6 signaling pathway for viral propagation.DR6 is not involved in the entry, replication, and translation steps of the HCV life cycle.Hepatitis C virus NS5A protein specifically interacts with DR6.
Title: Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation.
MiR20a5p functioned as an oncogene in HNSCC by downregulating TNFRSF21.
Title: Upregulated miR‑20a‑5p expression promotes proliferation and invasion of head and neck squamous cell carcinoma cells by targeting of TNFRSF21.
Knockdown death receptor 6 by shRNA in human pDCs cell line GEN2.2 significantly diminished the CpG-ODN induced IFN-regulatory factor 7 nuclear localization and IFN-I production.
Title: Death receptor 6 is a novel plasmacytoid dendritic cell-specific receptor and modulates type I interferon production.
data identify a new mechanism underlying tumour cell extravasation and metastasis, and suggest endothelial DR6-mediated necroptotic signalling pathways as targets for anti-metastatic therapies
Title: Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis.

Submit: New GeneRIF Correction See all GeneRIFs (29)

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

EBI GWAS Catalog

Description
Genome-wide association study of panic disorder in the Japanese population. 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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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of TNFRSF21	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

AL035172 (e-PCR)
- UniSTS:94725

TNFRSF21 (e-PCR)
- UniSTS:505650

AFM280vg9 (e-PCR)
- UniSTS:563

TNFRSF21_1271 (e-PCR)
- UniSTS:277830

TNFRSF21_v368 (e-PCR)
- UniSTS:277830

GDB:595836 (e-PCR)
- UniSTS:158031

SHGC-143324 (e-PCR)
- UniSTS:171856

RH123646 (e-PCR)
- UniSTS:136067

SHGC-106092 (e-PCR)
- UniSTS:169621

RH11030 (e-PCR)
- UniSTS:26803

RH78244 (e-PCR)
- UniSTS:21194

AL035169 (e-PCR)
- UniSTS:94705

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in adaptive immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in adaptive immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axonal fasciculation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
involved_in humoral immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in humoral immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in myelination	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of B cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of B cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-10 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-13 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-5 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of myelination	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of myelination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in oligodendrocyte apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in oligodendrocyte apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of oligodendrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tumor necrosis factor receptor superfamily member 21

Names: TNFR-related death receptor 6; death receptor 6

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.

mRNA and Protein(s)

NM_014452.5 → NP_055267.1 tumor necrosis factor receptor superfamily member 21 precursor

See identical proteins and their annotated locations for NP_055267.1

Status: REVIEWED

Source sequence(s)

AY358304, HY007775

Consensus CDS

CCDS4921.1

UniProtKB/Swiss-Prot

B2RDI9, O75509, Q0D2P5, Q96D86

UniProtKB/TrEMBL

B3KMB6

Related

ENSP00000296861.2, ENST00000296861.2

Conserved Domains (3) summary

cd08778
Location:414 → 497

Death_TNFRSF21; Death domain of tumor necrosis factor receptor superfamily member 21

cd10583
Location:53 → 211

TNFRSF21; Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor (DR6)

cl14633
Location:594 → 654

DD; Death Domain Superfamily of protein-protein interaction domains