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    TNFRSF25 TNF receptor superfamily member 25 [ Homo sapiens (human) ]

    Gene ID: 8718, updated on 9-Dec-2024

    Summary

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    Official Symbol
    TNFRSF25provided by HGNC
    Official Full Name
    TNF receptor superfamily member 25provided by HGNC
    Primary source
    HGNC:HGNC:11910
    See related
    Ensembl:ENSG00000215788 MIM:603366; AllianceGenome:HGNC:11910
    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
    DR3; TR3; DDR3; LARD; APO-3; TRAMP; WSL-1; GEF720; WSL-LR; PLEKHG5; TNFRSF12
    Summary
    The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed preferentially in the tissues enriched in lymphocytes, and it may play a role in regulating lymphocyte homeostasis. This receptor has been shown to stimulate NF-kappa B activity and regulate cell apoptosis. The signal transduction of this receptor is mediated by various death domain containing adaptor proteins. Knockout studies in mice suggested the role of this gene in the removal of self-reactive T cells in the thymus. Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported, most of which are potentially secreted molecules. The alternative splicing of this gene in B and T cells encounters a programmed change upon T-cell activation, which predominantly produces full-length, membrane bound isoforms, and is thought to be involved in controlling lymphocyte proliferation induced by T-cell activation. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in skin (RPKM 23.6), spleen (RPKM 13.2) and 19 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TNFRSF25 in Genome Data Viewer
    Location:
    1p36.31
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (6460786..6466173, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (5986428..5991815, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (6520846..6526233, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6483551-6484165 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6484166-6484779 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 153 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 154 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 82 Neighboring gene hes family bHLH transcription factor 2 Neighboring gene microRNA 4252 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6499737-6500250 Neighboring gene espin Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 155 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6501479-6501980 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6501981-6502480 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6503341-6503883 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 156 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6506945-6507603 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6507628-6508502 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6509377-6510250 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6512972-6513929 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:6518900-6519106 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 157 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6526054-6527002 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6534424-6534945 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6534946-6535466 Neighboring gene pleckstrin homology and RhoGEF domain containing G5 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:6536823-6538022 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 158 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 159 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 160 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr1:6555381-6556136 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 161 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6562565-6563294 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6566857-6567357 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6571620-6572434 Neighboring gene MPRA-validated peak31 silencer Neighboring gene Sharpr-MPRA regulatory region 8211 Neighboring gene Sharpr-MPRA regulatory region 5048 Neighboring gene nucleolar protein 9 Neighboring gene RNA, U6 small nuclear 731, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis. Filatova EN, et al. Acta Microbiol Immunol Hung, 2016 Sep. PMID 27682848
    2. Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene duplication is more prevalent in rheumatoid arthritis. Osawa K, et al. Genes Immun, 2004 Sep. PMID 15241467
    3. [DR3/LARD mRNA spliced variants' frequency at colorectal cancer]. Utkin OV, et al. Mol Biol (Mosk), 2013 Sep-Oct. PMID 25509355
    4. [Frequency of the occurrence of spliced variants of the messenger RNA DR3/LARD in herpesviral infection]. Utkin OV, et al. Vopr Virusol, 2014. PMID 25929035
    5. The role of death receptor 3 in the biological behavior of hepatocellular carcinoma cells. Zhang YC, et al. Mol Med Rep, 2015 Feb. PMID 25370568, Free PMC Article

    See all (77) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma.
      Title: Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma.
    2. Syndecan 4, galectin 2, and death receptor 3 (DR3) as novel proteins in pathophysiology of preeclampsia.
      Title: Syndecan 4, galectin 2, and death receptor 3 (DR3) as novel proteins in pathophysiology of preeclampsia.
    3. TL1A-DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1-Specific T Cell Responses.
      Title: TL1A-DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1-Specific T Cell Responses.
    4. The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens.
      Title: The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens.
    5. Pathologic up-regulation of TNFSF15-TNFRSF25 axis sustains endothelial dysfunction in unprovoked venous thromboembolism.
      Title: Pathologic up-regulation of TNFSF15-TNFRSF25 axis sustains endothelial dysfunction in unprovoked venous thromboembolism.
    6. The identifies a new inflammatory mechanism in Mucosal-associated invariant T cells linking the DR3/TL1A axis with amplification of TCR-dependent and -independent effector functions, particularly inducing excessive innate TNF-alpha production.
      Title: The TL1A-DR3 Axis Selectively Drives Effector Functions in Human MAIT Cells.
    7. In contrast to pre-menopausal females, post-menopausal serum levels of TL1A are not significantly elevated and that DR3 expression is not induced on CD14+ monocytes. Murine ovariectomy (OVX) model of estrogen-deficiency revealed that early post-OVX expression of DR3 on CD4+ T cells is significantly elevated suggesting that DR3 and TL1A could play a potentially indirect role in early post-menopausal bone loss.
      Title: Oestrogen-deficiency induces bone loss by modulating CD14(+) monocyte and CD4(+) T cell DR3 expression and serum TL1A levels.
    8. Findings clarify the process and consequences of death receptor 3 (DR3) signaling-induced intestinal inflammation through regulation of group 3 innate lymphoid cells (ILC3s).
      Title: Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation.
    9. Hypermethylation of the proapoptotic genes BCL2 L11 and TNFRSF25 is observed in pleomorphic adenoma of the salivary glands. However, this phenomenon did not impact mRNA transcription.
      Title: DNA methylation polymerase chain reaction (PCR) array of apoptosis-related genes in pleomorphic adenomas of the salivary glands.
    10. the DR3/TL1A pathway directly enhances human OC formation and resorptive activity, controlling expression and activation of CCL3 and MMP-9.
      Title: CCL3 and MMP-9 are induced by TL1A during death receptor 3 (TNFRSF25)-dependent osteoclast function and systemic bone loss.
    Submit: New GeneRIF Correction See all GeneRIFs (48)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables signaling receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables tumor necrosis factor receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in tumor necrosis factor-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular region 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 TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    tumor necrosis factor receptor superfamily member 25
    Names
    Guanine nucleotide exchange factor 720
    PH domain-containing family G member 5
    Pleckstrin homology domain-containing family G member 5
    apoptosis inducing receptor
    apoptosis-inducing receptor AIR
    apoptosis-mediating receptor DR3
    apoptosis-mediating receptor TRAMP
    death domain receptor 3 soluble form
    death receptor beta
    lymphocyte-associated receptor of death
    protein WSL-1
    tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein)

    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

    1. NG_029910.1 RefSeqGene

      Range
      5023..10410
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001039664.2 → NP_001034753.1  tumor necrosis factor receptor superfamily member 25 isoform 12 precursor

      See identical proteins and their annotated locations for NP_001034753.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (12) lacks several 3' exons and has an alternate 3' end, when compared to variant 1. The resulting isoform (12) has a distinct and shorter C-terminus, as compared to isoform 1.
      Source sequence(s)
      AY358309, U83598
      UniProtKB/TrEMBL
      A5LIN1
      Related
      ENST00000453341.1
      Conserved Domains (1) summary
      cd13420
      Location:32 → 145
      TNFRSF25; tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3)

    2. NM_003790.3 → NP_003781.1  tumor necrosis factor receptor superfamily member 25 isoform 2 precursor

      See identical proteins and their annotated locations for NP_003781.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two coding segments, both of which result in a frameshift, when compared to variant 1. The resulting isoform (2) has a shorter and distinct internal region, as compared to isoform 1.
      Source sequence(s)
      AL158217, BM666370, U74611
      Consensus CDS
      CCDS71.1
      UniProtKB/Swiss-Prot
      B1ALX2, B1ALX3, B7ZLL7, O00275, O00276, O00277, O00278, O00279, O00280, O14865, O14866, P78507, P78515, Q17RU4, Q92983, Q93036, Q93037, Q93038, Q99722, Q99830, Q99831, Q9BY86, Q9UME0, Q9UME1, Q9UME5
      UniProtKB/TrEMBL
      A0A3B3ISD9
      Related
      ENSP00000349341.3, ENST00000356876.8
      Conserved Domains (2) summary
      cd08815
      Location:334 → 410
      Death_TNFRSF25_DR3; Death domain of Tumor Necrosis Factor Receptor superfamily 25
      cd13420
      Location:32 → 145
      TNFRSF25; tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3)

    3. NM_148965.2 → NP_683866.1  tumor necrosis factor receptor superfamily member 25 isoform 1 precursor

      See identical proteins and their annotated locations for NP_683866.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AF026070, AL158217, BC143886, BM666370
      Consensus CDS
      CCDS72.1
      UniProtKB/TrEMBL
      A0A3B3ISD9
      Related
      ENSP00000367013.3, ENST00000377782.7
      Conserved Domains (2) summary
      cd08815
      Location:343 → 419
      Death_TNFRSF25_DR3; Death domain of Tumor Necrosis Factor Receptor superfamily 25
      cd13420
      Location:32 → 145
      TNFRSF25; tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3)

    4. NM_148966.2 → NP_683867.1  tumor necrosis factor receptor superfamily member 25 isoform 3 precursor

      See identical proteins and their annotated locations for NP_683867.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two coding segments, both of which result in a frameshift, when compared to variant 1. The resulting isoform (3) contains a distinct and shorter internal segment, as compared to isoform 1.
      Source sequence(s)
      AL158217, BC143886, BM666370
      Consensus CDS
      CCDS73.1
      UniProtKB/TrEMBL
      A0A3B3ISD9
      Related
      ENSP00000337713.5, ENST00000351959.9
      Conserved Domains (2) summary
      cd08815
      Location:297 → 373
      Death_TNFRSF25_DR3; Death domain of Tumor Necrosis Factor Receptor superfamily 25
      cd13420
      Location:32 → 145
      TNFRSF25; tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3)

    5. NM_148967.2 → NP_683868.1  tumor necrosis factor receptor superfamily member 25 isoform 4 precursor

      See identical proteins and their annotated locations for NP_683868.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks three coding segments, two of which result in a frameshift, when compared to variant 1. The resulting isoform (4) lacks an internal region, and contains a distinct and shorter internal segment, as compared to isoform 1.
      Source sequence(s)
      AL158217, AY358309, BM666370, U94509
      Consensus CDS
      CCDS74.1
      UniProtKB/TrEMBL
      A0A3B3ISD9
      Related
      ENSP00000314451.3, ENST00000348333.7
      Conserved Domains (2) summary
      cl14633
      Location:289 → 365
      DD; Death Domain Superfamily of protein-protein interaction domains
      cl22855
      Location:32 → 100
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

    6. NM_148970.2 → NP_683871.1  tumor necrosis factor receptor superfamily member 25 isoform 7 precursor

      See identical proteins and their annotated locations for NP_683871.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) lacks an in-frame coding segment compared to variant 1. The resulting isoform (7) lacks an internal region, as compared to isoform 1.
      Source sequence(s)
      AL158217, AY358309, BM666370, U94508
      Consensus CDS
      CCDS75.1
      UniProtKB/Swiss-Prot
      Q93038
      Related
      ENSP00000326762.3, ENST00000351748.7
      Conserved Domains (2) summary
      cl14633
      Location:151 → 227
      DD; Death Domain Superfamily of protein-protein interaction domains
      cl22855
      Location:32 → 53
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

    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

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      6460786..6466173 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      5986428..5991815 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_148968.1: Suppressed sequence

      Description
      NM_148968.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    2. NM_148969.1: Suppressed sequence

      Description
      NM_148969.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    3. NM_148971.1: Suppressed sequence

      Description
      NM_148971.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.

    4. NM_148972.1: Suppressed sequence

      Description
      NM_148972.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.

    5. NM_148973.1: Suppressed sequence

      Description
      NM_148973.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.

    6. NM_148974.1: Suppressed sequence

      Description
      NM_148974.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q93038.2 GenPept UniProtKB/Swiss-Prot:Q93038

    Gene LinkOut

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

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