Property Summary

NCBI Gene PubMed Count 95
Grant Count 256
R01 Count 123
Funding $24,618,798.1
PubMed Score 264.59
PubTator Score 160.49

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma -1.410 0.000
medulloblastoma, large-cell -1.200 0.000
pancreatic ductal adenocarcinoma liver m... 1.210 0.013

Synonym

Accession Q92956 B3KW30 B9DI89 Q6IB95 Q8N634 Q8WXR1 Q96J31 Q9UM65
Symbols TR2
ATAR
HVEA
HVEM
CD270
LIGHTR

Gene

PDB

4RSU   1JMA   2AW2   4FHQ  

Gene RIF (66)

PMID Text
26650888 In eight cases (42%) we observed recurrent copy number loss of chr1:2,352,236-4,574,271, a region containing the candidate tumor suppressor TNFRSF14.
26202493 Study report the crystal structure of unbound HVEM, which further contributes to the understanding of the molecular mechanisms controlling recognition between HVEM and its ligands.
25750286 HVEM may play a critical role in tumor progression and immune evasion
25468715 Data indicate that tumour-expressing herpes virus entry mediator (HVEMplays a critical role in hepatocellular carcinoma (HCC), suggesting targeting HVEM may be a promising therapeutic strategy for HCC.
24980868 Relative expression of HVEM and LTbetaR modulates canonical NF-kappaB and pro-apoptotic signals stimulated by LIGHT.
24314649 The conformation of the N-terminus of herpes simplex virus gD is induced by direct binding to HVEM and nectin-1.
24249528 HVEM plays a critical role in both tumor progression and the evasion of host antitumor immune responses, possibly through direct and indirect mechanisms.
24162774 HIV-1 gp120 upregulates the expression of tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) in human B cells
23976978 HVEM gene polymorphisms are associated with sporadic breast cancer in Chinese women.
23761635 HVEM functions as a regulator of immune function that activates NK cells via CD160 and limits lymphocyte-induced inflammation via association with B and T lymphocyte attenuator
23470321 Studies indicate co-stimulatory and co-inhibitory receptors B7-1, B7-2, CD28 and TNFRSF14 have a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signalling.
23445872 Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in pediatric follicular lymphoma.
23375291 BTLA and HVEM may have roles in graft rejection after kidney transplantation
23333304 HIV-1 gp120 upregulates the expression of tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) in human B cells
22634623 HVEM-B and T lymphocyte attenuator (BTLA) interactions impair minor histocompatibility antigen (MiHA)-specific T cell functionality, providing a rationale for interfering with BTLA signaling in post-stem cell transplantation.
22459947 These findings support role for BTLA and/or HVEM as potential, novel diagnostic markers of innate immune response/status and as therapeutic targets of sepsis.
22239829 These results suggest that the C-terminal portion of the soluble HVEM ectodomain inhibits herpes simplex virus type 1 gD activation and that this effect is neutralized in the full-length form of HVEM in normal infection.
22179929 study described the expression and spatial distribution of HVEM and BTLA in rheumatoid arthritis synovial tissues, and results indicated that HVEM/BTLA may be involved in regulating the progress of joint inflammation
22113134 Results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of gastric cancer.
21959263 The results of a mutagenesis study of HVEM suggest that the CD160 binding region on HVEM was slightly different from, but overlapped with, the BTLA binding site.
21941365 TNFRSF14 appears to be a serious candidate gene that might contribute to follicular lymphoma development.
21920726 HVEM-BTLA cis complex provides intrinsic regulation in T cells serving as an interference mechanism silencing signals coming from the microenvironment.
21533159 data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells
20962851 Polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replication-TNFRSF6B-rs4809330(*)A: P=0.028, OR=1.13; TNFRSF14-rs6684865(*)A: overall P=0.0008, OR=1.2.
20962851 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20884631 Findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes.
20884631 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20568250 Observational study of gene-disease association. (HuGE Navigator)
20439292 Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
20233754 Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator)
20187130 We have identified and replicated a novel gene-gene interaction between 2 polymorphisms of TNFRSF members in Spanish patients with RA, based on the hypothesis of shared pathogenic pathways in complex diseases.
20187130 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20066438 Observational study of gene-disease association. (HuGE Navigator)
19915044 the HVEM-BTLA cis-complex competitively inhibits HVEM activation by ligands expressed in the surrounding microenvironment, thus helping maintain T cells in the naive state.
19773279 Observational study of gene-disease association. (HuGE Navigator)
19762537 results suggest that down-regulation of the BTLA-HVEM pathway may be involved in germinal center B-cell activation.
19701890 unknown killing effect of LIGHT through HVEM on a lymphoid malignancy is described.
19680232 Results provide evidence of an existing relationship between HVEM and obesity, which suggest that this TNF superfamily receptor could be involved in the pathogenesis of obesity and inflammation-related activity.
19573080 Observational study of gene-disease association. (HuGE Navigator)
19473566 tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) and signal regulatory protein, gamma (SIRPG) appear to contribute to gender difference in incidence of systemic lupus erythematosus.
19332782 HVEM-B and T lymphocyte attenuator bidirectional signaling may serve as a critical cell-survival system for lymphoid and epithelial cells
19110536 Observational study of gene-disease association. (HuGE Navigator)
19023130 LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways.
18987746 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
18794853 Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator)
18671825 These results establish that HVEM is involved in NF-kappaB activation by herpes simplex virus 1 glycoprotein D.
18502984 Expression of entry receptors nectin-1 and HVEM prevent entry of HSV-1 into human conjunctival epithelium.
18193050 CD160 serves as a negative regulator of CD4+ T cell activation through its interaction with HVEM.
17947707 Ca(2+)is a downstream mediator of the LIGHT/HVEM interaction in monocytes
17405920 HSV-1-gD-HveA interaction initiates a signal transduction pathway leading to NF-kappaB activation
17010447 HVEM, a membrane-bound receptor that protects against apoptosis, was expressed only on syncytiotrophoblast
16797773 Real-time RT-PCR confirmed up-regulation of IL-8, osteopontin, and TNFRSF14 and down-regulation of SAMeS and CD209 in AH.
16169851 2.8-A crystal structure of the BTLA-HVEM complex shows that BTLA binds the N-terminal cysteine-rich domain of HVEM and employs a unique binding surface
16131544 distinct herpesviruses target the HVEM-BTLA cosignaling pathway, suggesting the importance of this pathway in regulating T cell activation during host defenses.
15917993 both LTbetaR and HVEM can discriminatively mediate the expression of different genes in cultured human umbilical vein endothelial cells, including LIGHT, a proinflammatory cytokine
15767456 in cells a complex forms through physical associations of HVEM, HSV-1 gD, and at least gH
15647361 Binding of HVEM to BTLA attenuates T cell activation, identifying HVEM/BTLA as a coinhibitory receptor pair.
15568026 HVEM binds to B T lymphocyte attenuator (BTLA), an Ig family member, which inhibits T cell proliferation.
15301860 Observational study of genotype prevalence. (HuGE Navigator)
15110526 both nectin 1 and HVEM receptors play a role during HSV infection in vivo and both are highly efficient even at low levels of expression
14749527 sHVEM levels were elevated in sera of patients with allergic asthma, atopic dermatitis and rheumatoid arthritis
12915568 association of HVEM and nectin-1 with lipid rafts during herpes simplex virus entry
12466117 Data show that mRNA encoding LIGHT and its receptors [HVEM, LTbetaR, and TR6 (DcR3)] are present in placentas and cytotrophoblast cells at term.
11976496 Crystallization and preliminary diffraction studies of the ectodomain of the envelope glycoprotein D from herpes simplex virus 1 alone and in complex with the ectodomain of the human receptor HveA
11742858 Data suggest involvement of TNF superfamily receptor members and ligands in human atherosclerosis. TNFRSF14 (HVEM, TR2, LIGHTR)analysis, found this receptor in regions rich in CD68-positive macrophage-derived foam cells and HLA-DR-positive cells.

AA Sequence

MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGEL      1 - 70
TGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRA     71 - 140
YATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWVWWFLSGSL    141 - 210
VIVIVCSTVGLIICVKRRKPRGDVVKVIVSVQRKRQEAEGEATVIEALQAPPDVTTVAVEETIPSFTGRS    211 - 280
PNH                                                                       281 - 283
//

Text Mined References (98)

PMID Year Title
26977880 2016 Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.
26650888 2016 Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma.
26202493 2015 Increased Heterologous Protein Expression in Drosophila S2 Cells for Massive Production of Immune Ligands/Receptors and Structural Analysis of Human HVEM.
25750286 2015 HVEM expression contributes to tumor progression and prognosis in human colorectal cancer.
25468715 2015 Clinical impact of herpesvirus entry mediator expression in human hepatocellular carcinoma.
24980868 2014 Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin ? receptor (LT?R) in human cells stimulated by the shared ligand LIGHT.
24449572 2014 Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.
24314649 2014 Induction of conformational changes at the N-terminus of herpes simplex virus glycoprotein D upon binding to HVEM and nectin-1.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24249528 2014 Significant involvement of herpesvirus entry mediator in human esophageal squamous cell carcinoma.
23976978 2013 HVEM gene polymorphisms are associated with sporadic breast cancer in Chinese women.
23761635 2013 CD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cytolytic function by NK cells.
23470321 2013 Molecular mechanisms of T cell co-stimulation and co-inhibition.
23445872 2013 Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas.
23375291 B- and T-lymphocyte attenuator/herpes virus entry mediator as early indicators for acute rejection following kidney transplantation.
23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
22801499 2012 HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria.
22634623 2012 B and T lymphocyte attenuator mediates inhibition of tumor-reactive CD8+ T cells in patients after allogeneic stem cell transplantation.
22459947 2012 BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction.
22239829 2012 The soluble amino-terminal region of HVEM mediates efficient herpes simplex virus type 1 infection of gD receptor-negative cells.
22179929 2012 The expression and anatomical distribution of BTLA and its ligand HVEM in rheumatoid synovium.
22113134 2012 The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients.
22017438 2011 The signaling networks of the herpesvirus entry mediator (TNFRSF14) in immune regulation.
21959263 2011 Molecular basis for herpesvirus entry mediator recognition by the human immune inhibitory receptor CD160 and its relationship to the cosignaling molecules BTLA and LIGHT.
21941365 2012 High rate of TNFRSF14 gene alterations related to 1p36 region in de novo follicular lymphoma and impact on prognosis.
21920726 2011 TNF Superfamily Networks: bidirectional and interference pathways of the herpesvirus entry mediator (TNFSF14).
21533159 2011 HVEM signalling promotes colitis.
21297633 2011 Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
20962851 2011 Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition.
20884631 2010 Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis.
20568250 2010 Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut.
20453842 2010 Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
20439292 2010 Genetic variants in the prediction of rheumatoid arthritis.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20233754 2010 Cumulative association of 22 genetic variants with seropositive rheumatoid arthritis risk.
20190752 2010 Multiple common variants for celiac disease influencing immune gene expression.
20187130 2010 Evidence of epistasis between TNFRSF14 and TNFRSF6B polymorphisms in patients with rheumatoid arthritis.
20066438 2010 PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis.
19915044 2009 T cell intrinsic heterodimeric complexes between HVEM and BTLA determine receptivity to the surrounding microenvironment.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19762537 2009 High expression of the inhibitory receptor BTLA in T-follicular helper cells and in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.
19701890 2009 A role for HVEM, but not lymphotoxin-beta receptor, in LIGHT-induced tumor cell death and chemokine production.
19680232 2010 Characterization of herpes virus entry mediator as a factor linked to obesity.
19573080 2009 Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
19473566 Changes in the gene expression of peripheral blood mononuclear cells during the menstrual cycle of females is associated with a gender bias in the incidence of systemic lupus erythematosus.
19342625 2009 IL-22-dependent attenuation of T cell-dependent (ConA) hepatitis in herpes virus entry mediator deficiency.
19332782 2009 Unconventional ligand activation of herpesvirus entry mediator signals cell survival.
19110536 2009 Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus.
19023130 2009 Inflammatory interaction between LIGHT and proteinase-activated receptor-2 in endothelial cells: potential role in atherogenesis.
18987746 2008 Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.
18794853 2008 Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
18671825 2008 Involvement of HVEM receptor in activation of nuclear factor kappaB by herpes simplex virus 1 glycoprotein D.
18519647 2008 A crucial role for HVEM and BTLA in preventing intestinal inflammation.
18502984 2008 HVEM and nectin-1 are the major mediators of herpes simplex virus 1 (HSV-1) entry into human conjunctival epithelium.
18193050 2008 CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17947707 2007 HVEM signaling in monocytes is mediated by intracellular calcium mobilization.
17474147 2007 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
17405920 2007 Signaling pathway used by HSV-1 to induce NF-kappaB activation: possible role of herpes virus entry receptor A.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17192395 2007 Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins.
17010447 2007 Differential cellular expression of LIGHT and its receptors in early gestation human placentas.
16932752 2006 Balancing co-stimulation and inhibition with BTLA and HVEM.
16797773 2006 Intrahepatic gene expression in human alcoholic hepatitis.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16169851 2005 Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex.
16131544 2005 Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway.
15917993 2005 Proinflammatory effects of LIGHT through HVEM and LTbetaR interactions in cultured human umbilical vein endothelial cells.
15767456 2005 Herpes simplex virus entry mediator associates in infected cells in a complex with viral proteins gD and at least gH.
15647361 2005 A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator.
15568026 2005 B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15340161 2004 Signal peptide prediction based on analysis of experimentally verified cleavage sites.
15301860 2004 Identification of single nucleotide polymorphisms in the tumor necrosis factor (TNF) and TNF receptor superfamily in the Korean population.
15110526 2004 Comparative usage of herpesvirus entry mediator A and nectin-1 by laboratory strains and clinical isolates of herpes simplex virus.
14749527 2003 High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12975309 2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.
12915568 2003 Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12466117 2002 Differential expression of LIGHT and its receptors in human placental villi and amniochorion membranes.
12093804 2002 Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor.
11976496 2002 Crystallization and preliminary diffraction studies of the ectodomain of the envelope glycoprotein D from herpes simplex virus 1 alone and in complex with the ectodomain of the human receptor HveA.
11756979 2002 Search for polymorphisms in the genes for herpesvirus entry mediator, nectin-1, and nectin-2 in immune seronegative individuals.
11742858 2001 Tumor necrosis factor receptor and ligand superfamily family members TNFRSF14 and LIGHT: new players in human atherogenesis.
11511370 2001 Herpes simplex virus glycoprotein D bound to the human receptor HveA.
11463856 2001 The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases.
11390428 2001 Modulation of T-cell responses to alloantigens by TR6/DcR3.
11279055 2001 A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains.
11035077 2000 Reciprocal expression of the TNF family receptor herpes virus entry mediator and its ligand LIGHT on activated T cells: LIGHT down-regulates its own receptor.
10706119 2000 APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death.
10318773 1999 A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis.
9696799 1998 Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry.
9462508 1998 LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator.
9162061 1997 A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation.
9162022 1997 Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1.
9153189 1997 ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.
8898196 1996 Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family.