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    TNFRSF14 TNF receptor superfamily member 14 [ Homo sapiens (human) ]

    Gene ID: 8764, updated on 3-Apr-2024

    Summary

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    Official Symbol
    TNFRSF14provided by HGNC
    Official Full Name
    TNF receptor superfamily member 14provided by HGNC
    Primary source
    HGNC:HGNC:11912
    See related
    Ensembl:ENSG00000157873 MIM:602746; AllianceGenome:HGNC:11912
    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
    TR2; ATAR; HVEA; HVEM; CD270; LIGHTR
    Summary
    This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
    Expression
    Ubiquitous expression in spleen (RPKM 22.9), duodenum (RPKM 21.7) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    1p36.32
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (2554234..2563829)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (1997007..2005473)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (2487810..2495268)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene pantothenate kinase 4 (inactive) Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2454755-2455542 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2458062-2458782 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2459504-2460224 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr1:2460225-2460944 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:2461459-2461962 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2463669-2464169 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2465753-2466256 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:2466257-2466760 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:2466761-2467264 Neighboring gene hes family bHLH transcription factor 5 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:2474412-2475282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2476154-2477024 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:2479637-2480506 Neighboring gene TNFRSF14 antisense RNA 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:2481723-2482922 Neighboring gene uncharacterized LOC100996583 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2498904-2499776 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2508969-2509605 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:2519024-2519656 Neighboring gene peroxiredoxin like 2B Neighboring gene membrane metalloendopeptidase like 1

    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. HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions. Duan L, et al. J Ovarian Res, 2020 Apr 20. PMID 32312328, Free PMC Article
    2. Herpes Virus Entry Mediator (HVEM): A Novel Potential Mediator of Trauma-Induced Immunosuppression. Wakeley ME, et al. J Surg Res, 2020 Jan. PMID 31522034, Free PMC Article
    3. Significance of Herpesvirus Entry Mediator Expression in Human Colorectal Liver Metastasis. Sasaki Y, et al. Ann Surg Oncol, 2019 Nov. PMID 31313042
    4. Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma. Han MZ, et al. EBioMedicine, 2019 May. PMID 30987862, Free PMC Article
    5. Soluble Fc-Disabled Herpes Virus Entry Mediator Augments Activation and Cytotoxicity of NK Cells by Promoting Cross-Talk between NK Cells and Monocytes. Meng Q, et al. J Immunol, 2019 Apr 1. PMID 30770415, Free PMC Article

    See all (146) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.
      Title: Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.
    2. MIF promotes Th17 cell differentiation in Hashimoto's thyroiditis by binding HVEM and activating NF-kappaB signaling pathway.
      Title: MIF promotes Th17 cell differentiation in Hashimoto's thyroiditis by binding HVEM and activating NF-κB signaling pathway.
    3. Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1[-] stem cell-like T cells over PD-1[+] T cells curbing tumor progression.
      Title: Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression.
    4. Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2.
      Title: Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2.
    5. BTLA inhibition has a dominant role in the cis-complex of BTLA and HVEM.
      Title: BTLA inhibition has a dominant role in the cis-complex of BTLA and HVEM.
    6. The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases.
      Title: The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases.
    7. Clinical Significance of BTLA and HVEM Expression on Circulating CD4(+) T and CD8(+) T Cells in Chronic Hepatitis B Virus Infection.
      Title: Clinical Significance of BTLA and HVEM Expression on Circulating CD4(+) T and CD8(+) T Cells in Chronic Hepatitis B Virus Infection.
    8. HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.
      Title: HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.
    9. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.
      Title: Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.
    10. Redesigning HVEM Interface for Selective Binding to LIGHT, BTLA, and CD160.
      Title: Redesigning HVEM Interface for Selective Binding to LIGHT, BTLA, and CD160.
    Submit: New GeneRIF Correction See all GeneRIFs (96)

    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
    Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
    EBI GWAS Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
    EBI GWAS Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    EBI GWAS Catalog
    Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.
    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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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) in human B cells PubMed
    Vif vif HIV-1 Vif downregulates the expression of tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) in Vif-expression T cells 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

    • FLJ26662

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables tumor necrosis factor receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables virus receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell costimulation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in defense response to Gram-negative bacterium IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in defense response to Gram-positive bacterium IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of adaptive immune memory response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of alpha-beta T cell proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of T cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of cytokine production involved in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of peptidyl-tyrosine phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in symbiont entry into host cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tumor necrosis factor-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in external side of 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 14
    Names
    CD40-like protein
    herpes virus entry mediator A
    tumor necrosis factor receptor superfamily, member 14 (herpesvirus entry mediator)
    tumor necrosis factor receptor-like gene2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_047096.1 RefSeqGene

      Range
      5007..12465
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001297605.2 → NP_001284534.1  tumor necrosis factor receptor superfamily member 14 isoform 2 precursor

      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 encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      BX343044, CD366981, DC383433
      UniProtKB/TrEMBL
      F6UPZ7
      Conserved Domains (1) summary
      cd10582
      Location:42 → 142
      TNFRSF14; Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM)

    2. NM_003820.4 → NP_003811.2  tumor necrosis factor receptor superfamily member 14 isoform 1 precursor

      See identical proteins and their annotated locations for NP_003811.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      CD366981, DC383433, U70321
      Consensus CDS
      CCDS44046.1
      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65
      UniProtKB/TrEMBL
      F6Q0M4
      Related
      ENSP00000347948.4, ENST00000355716.5
      Conserved Domains (3) summary
      cd00185
      Location:138 → 186
      TNFRSF; CRD2 [structural motif]
      cd10582
      Location:42 → 142
      TNFRSF14; Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM)
      cl22855
      Location:98 → 196
      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
      2554234..2563829
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433419.1 → XP_047289375.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    2. XM_047433418.1 → XP_047289374.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    3. XM_047433414.1 → XP_047289370.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    4. XM_047433412.1 → XP_047289368.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65
      Related
      ENSP00000399292.2, ENST00000435221.6

    5. XM_047433416.1 → XP_047289372.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65
      Related
      ENSP00000399533.1, ENST00000451778.5

    6. XM_047433413.1 → XP_047289369.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65
      Related
      ENSP00000415254.1, ENST00000434817.5

    7. XM_047433422.1 → XP_047289378.1  tumor necrosis factor receptor superfamily member 14 isoform X4

      UniProtKB/TrEMBL
      B9A034
      Related
      ENSP00000386859.1, ENST00000409119.5

    8. XM_006711019.3 → XP_006711082.1  tumor necrosis factor receptor superfamily member 14 isoform X3

      See identical proteins and their annotated locations for XP_006711082.1

      UniProtKB/TrEMBL
      F6UPZ7
      Conserved Domains (1) summary
      cd10582
      Location:42 → 142
      TNFRSF14; Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM)

    9. XM_047433421.1 → XP_047289377.1  tumor necrosis factor receptor superfamily member 14 isoform X4

      UniProtKB/TrEMBL
      B9A034
      Related
      ENSP00000411854.1, ENST00000426449.5

    10. XM_047433423.1 → XP_047289379.1  tumor necrosis factor receptor superfamily member 14 isoform X5

    11. XM_011542383.3 → XP_011540685.1  tumor necrosis factor receptor superfamily member 14 isoform X2

      See identical proteins and their annotated locations for XP_011540685.1

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187515.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      106553..115019
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328613.1 → XP_054184588.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    2. XM_054328611.1 → XP_054184586.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    3. XM_054328610.1 → XP_054184585.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    4. XM_054328618.1 → XP_054184593.1  tumor necrosis factor receptor superfamily member 14 isoform X4

      UniProtKB/TrEMBL
      B9A034

    5. XM_054328612.1 → XP_054184587.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    6. XM_054328614.1 → XP_054184589.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    7. XM_054328616.1 → XP_054184591.1  tumor necrosis factor receptor superfamily member 14 isoform X3

    8. XM_054328617.1 → XP_054184592.1  tumor necrosis factor receptor superfamily member 14 isoform X4

      UniProtKB/TrEMBL
      B9A034

    9. XM_054328619.1 → XP_054184594.1  tumor necrosis factor receptor superfamily member 14 isoform X5

    10. XM_054328609.1 → XP_054184584.1  tumor necrosis factor receptor superfamily member 14 isoform X7

    11. XM_054328608.1 → XP_054184583.1  tumor necrosis factor receptor superfamily member 14 isoform X6

    12. XM_054328615.1 → XP_054184590.1  tumor necrosis factor receptor superfamily member 14 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      1997007..2005473
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339412.1 → XP_054195387.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    2. XM_054339410.1 → XP_054195385.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    3. XM_054339409.1 → XP_054195384.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    4. XM_054339417.1 → XP_054195392.1  tumor necrosis factor receptor superfamily member 14 isoform X4

      UniProtKB/TrEMBL
      B9A034

    5. XM_054339411.1 → XP_054195386.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    6. XM_054339413.1 → XP_054195388.1  tumor necrosis factor receptor superfamily member 14 isoform X1

      UniProtKB/Swiss-Prot
      B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

    7. XM_054339415.1 → XP_054195390.1  tumor necrosis factor receptor superfamily member 14 isoform X3

    8. XM_054339416.1 → XP_054195391.1  tumor necrosis factor receptor superfamily member 14 isoform X4

      UniProtKB/TrEMBL
      B9A034

    9. XM_054339418.1 → XP_054195393.1  tumor necrosis factor receptor superfamily member 14 isoform X5

    10. XM_054339408.1 → XP_054195383.1  tumor necrosis factor receptor superfamily member 14 isoform X9

    11. XM_054339407.1 → XP_054195382.1  tumor necrosis factor receptor superfamily member 14 isoform X8

    12. XM_054339414.1 → XP_054195389.1  tumor necrosis factor receptor superfamily member 14 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92956.3 GenPept UniProtKB/Swiss-Prot:Q92956

    Gene LinkOut

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

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