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

Gene ID: 8718, updated on 5-Mar-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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Location:
1p36.31
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (6460786..6466173, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (5986428..5991815, complement)
105.20220307 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. Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation. Li J, et al. Nat Commun, 2019 Jul 29. PMID 31358760, Free PMC Article
  2. 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
  3. Death receptor 3 mediates necroptotic cell death. Bittner S, et al. Cell Mol Life Sci, 2017 Feb. PMID 27592300
  4. Expression of death receptor 3 on peripheral blood mononuclear cells differes in adult IBD patients and children with newly diagnosed IBD. Slebioda TJ, et al. Cytometry B Clin Cytom, 2017 Mar. PMID 27001939
  5. [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

See all (76) 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)

Genotypes

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_2023_10

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

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