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

    Gene ID: 27242, updated on 11-Apr-2024

    Summary

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    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

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    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_000006.12Genomic Context describing neighboring genes Neighboring gene adhesion G protein-coupled receptor F1 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:47011981-47013180 Neighboring gene MPRA-validated peak5829 silencer Neighboring gene Sharpr-MPRA regulatory region 10363 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_92032 Neighboring gene uncharacterized LOC105375081 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24655 Neighboring gene MPRA-validated peak5831 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24656 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24657 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:47252971-47254170 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24658 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:47276592-47277314 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24659 Neighboring gene Sharpr-MPRA regulatory region 4111 Neighboring gene NANOG hESC enhancer GRCh37_chr6:47306925-47307426 Neighboring gene uncharacterized LOC105375082 Neighboring gene B3GNTL1 pseudogene 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Death Receptor 6 as a Prognostic Marker in Low-grade Glioma. Stegmann SK, et al. Anticancer Res, 2022 Mar. PMID 35220214
    2. circTNFRSF21, a newly identified circular RNA promotes endometrial carcinoma pathogenesis through regulating miR-1227-MAPK13/ATF2 axis. Liu Y, et al. Aging (Albany NY), 2020 Apr 16. PMID 32299063, Free PMC Article
    3. TNFRSF21 mutations cause high myopia. Pan H, et al. J Med Genet, 2019 Oct. PMID 31189563
    4. Upregulated miR‑20a‑5p expression promotes proliferation and invasion of head and neck squamous cell carcinoma cells by targeting of TNFRSF21. Wu H, et al. Oncol Rep, 2018 Aug. PMID 29901115
    5. Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation. Luong TTD, et al. Sci Rep, 2017 Jul 25. PMID 28743875, Free PMC Article

    See all (53) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. Death Receptor 6 as a Prognostic Marker in Low-grade Glioma.
      Title: Death Receptor 6 as a Prognostic Marker in Low-grade Glioma.
    4. 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.
    5. 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.
    6. Variants in TNFRSF21 cause non-syndromic high myopia in Chinese population.
      Title: TNFRSF21 mutations cause high myopia.
    7. 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.
    8. 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.
    9. 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.
    10. 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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC31965

    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)

    1. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      47231532..47309905 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      47068690..47147063 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75509.1 GenPept UniProtKB/Swiss-Prot:O75509

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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