Browse TNFRSF14

Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Membrane Single-pass type I membrane protein
Domain PF00020 TNFR/NGFR cysteine-rich region
Function

Receptor for BTLA. Receptor for TNFSF14/LIGHT and homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte activation. Plays an important role in HSV pathogenesis because it enhanced the entry of several wild-type HSV strains of both serotypes into CHO cells, and mediated HSV entry into activated human T-cells. ; FUNCTION: (Microbial infection) Acts as a receptor for Herpes simplex virus 1/HHV-1. ; FUNCTION: (Microbial infection) Acts as a receptor for Herpes simplex virus 2/HHV-2.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0002237 response to molecule of bacterial origin
GO:0002367 cytokine production involved in immune response
GO:0002374 cytokine secretion involved in immune response
GO:0002440 production of molecular mediator of immune response
GO:0002683 negative regulation of immune system process
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0002694 regulation of leukocyte activation
GO:0002695 negative regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002718 regulation of cytokine production involved in immune response
GO:0002720 positive regulation of cytokine production involved in immune response
GO:0002739 regulation of cytokine secretion involved in immune response
GO:0002741 positive regulation of cytokine secretion involved in immune response
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0009306 protein secretion
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019058 viral life cycle
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030260 entry into host cell
GO:0030335 positive regulation of cell migration
GO:0031294 lymphocyte costimulation
GO:0031295 T cell costimulation
GO:0032496 response to lipopolysaccharide
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032945 negative regulation of mononuclear cell proliferation
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034612 response to tumor necrosis factor
GO:0040017 positive regulation of locomotion
GO:0042098 T cell proliferation
GO:0042110 T cell activation
GO:0042129 regulation of T cell proliferation
GO:0042130 negative regulation of T cell proliferation
GO:0042742 defense response to bacterium
GO:0043410 positive regulation of MAPK cascade
GO:0044409 entry into host
GO:0045785 positive regulation of cell adhesion
GO:0046631 alpha-beta T cell activation
GO:0046633 alpha-beta T cell proliferation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046636 negative regulation of alpha-beta T cell activation
GO:0046640 regulation of alpha-beta T cell proliferation
GO:0046642 negative regulation of alpha-beta T cell proliferation
GO:0046651 lymphocyte proliferation
GO:0046718 viral entry into host cell
GO:0050663 cytokine secretion
GO:0050670 regulation of lymphocyte proliferation
GO:0050672 negative regulation of lymphocyte proliferation
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050829 defense response to Gram-negative bacterium
GO:0050830 defense response to Gram-positive bacterium
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050866 negative regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050868 negative regulation of T cell activation
GO:0050870 positive regulation of T cell activation
GO:0050900 leukocyte migration
GO:0051047 positive regulation of secretion
GO:0051222 positive regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051272 positive regulation of cellular component movement
GO:0051701 interaction with host
GO:0051806 entry into cell of other organism involved in symbiotic interaction
GO:0051828 entry into other organism involved in symbiotic interaction
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070664 negative regulation of leukocyte proliferation
GO:0071356 cellular response to tumor necrosis factor
GO:0071593 lymphocyte aggregation
GO:0072676 lymphocyte migration
GO:0072678 T cell migration
GO:0098542 defense response to other organism
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903038 negative regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903532 positive regulation of secretion by cell
GO:1904951 positive regulation of establishment of protein localization
GO:2000147 positive regulation of cell motility
GO:2000401 regulation of lymphocyte migration
GO:2000403 positive regulation of lymphocyte migration
GO:2000404 regulation of T cell migration
GO:2000406 positive regulation of T cell migration
Molecular Function GO:0001618 virus receptor activity
GO:0005031 tumor necrosis factor-activated receptor activity
GO:0005035 death receptor activity
GO:0031625 ubiquitin protein ligase binding
GO:0044389 ubiquitin-like protein ligase binding
Cellular Component GO:0009897 external side of plasma membrane
GO:0098552 side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-388841: Costimulation by the CD28 family
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-5669034: TNFs bind their physiological receptors
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TNFRSF14 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TNFRSF14 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25468715Hepatocellular CarcinomaInhibit immunity (infiltration)Furthermore, HVEM status was inversely correlated with tumour-infiltrating CD4(+), CD8(+) and CD45RO(+) lymphocytes. In addition, it was also associated with reduced expression of perforin, granzyme B and interferon-γ (IFN-γ). Taken together, tumour-expressing HVEM plays a functionally important role in HCC.
22547582Chronic Lymphocytic LeukemiaInhibit immunityIn the present study, we show via functional screening assays that CD200, CD270, CD274, and CD276 are coopted by CLL cells to induce impaired actin synapse formation in both allogeneic and autologous T cells.
27693350Diffuse Large B-Cell Lymphoma Germinal Center B-Cell TypePromote immunityLoss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas.
27418644Plasma cell myelomaInhibit immunity (T cell function)The immune checkpoint molecules programmed death ligand 1 (PD-L1), Galectin-9, herpesvirus entry mediator (HVEM), and CD200, as well as T-cell metabolism regulators indoleamine 2, 3-dioxygenase (IDO), and CD38 are significantly upregulated during osteoclastogenesis.
27418644Plasma cell myelomaInhibit immunityWhen targeted by an anti-CD38 mAb, suppressive T-cell function by OCs is alleviated, associated with downregulation of HVEM and IDO.
28470686Pancreatic Carcinoma; Ampulla of Vater CarcinomaInhibit immunity (T cell function)Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p?=?0.002), Gal-9 (p?=?0.003), HVEM (p?=?0.001), IDO (p?=?0.049), HLA-G (p?=?0.004) and high CD8/FoxP3 TIL ratio (p?=?0.006) were associated with improved cancer-specific survival.
19701890LeukemiaPromote immunityThe TNF member LIGHT also known as TL4 or TNFSF14) can play a major role in cancer control via its two receptors; it induces tumor cell death through lymphotoxin-beta receptor (LT-betaR) and ligation to the herpes virus entry mediator (HVEM) amplifies the immune response. By studying the effect of LIGHT in the transcriptional profile of a lymphoid malignancy, we found that HVEM, but not LT-betaR, stimulation induces a significant increase in the expression of chemokine genes such as IL-8, and an unexpected upregulation of apoptotic genes. This had functional consequences, since LIGHT, or HVEM mAb, thus far known to costimulate T- and B-cell activation, induced chronic lymphocytic leukemia cell death. Many of the mediators involved were identified here, with an apoptotic pathway as demonstrated by caspases activation, decrease in mitochondrial membrane potential, upregulation of the pro-apoptotic protein Bax, but also a role of TRAIL. HVEM Moreover, HVEM induced endogenous TNF-alpha production and TNF-alpha enhanced HVEM-mediated cell death.
23692853LymphomaInhibit immunity (T cell function); immunotherapy targetBTLA was strongly expressed at the surface of resting Vγ9Vδ2 T cells and inversely correlated with T-cell differentiation. BTLA-HVEM blockade by monoclonal antibodies resulted in the enhancement of Vγ9Vδ2 T-cell receptor-mediated signaling, whereas BTLA-HVEM interaction led to a decrease in phosphoantigen-mediated proliferation by inducing a partial S-phase arrest. These data suggest that HVEM interaction with BTLA may play a role in lymphomagenesis by interfering with Vγ9Vδ2 T-cell proliferation.
24249528Esophageal Squamous Cell CarcinomaInhibit immunityHVEM expression was found to be significantly correlated with depth of tumor invasion and lymph node metastasis. Furthermore, it was found to be inversely correlated with tumor-infiltrating CD4(+) , CD8(+) , and CD45RO(+) lymphocytes.
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TNFRSF14 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TNFRSF14 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1330.811
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1550.96
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3470.882
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4410.375
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0860.972
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.8960.784
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.150.74
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0060.997
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3860.862
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.0560.627
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2110.709
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3020.00231
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TNFRSF14 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.74.1-0.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.75.1-1.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNFRSF14. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNFRSF14. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNFRSF14.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNFRSF14. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TNFRSF14 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TNFRSF14 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTNFRSF14
Nametumor necrosis factor receptor superfamily, member 14
Aliases HVEM; ATAR; LIGHTR; HVEA; CD270; herpesvirus entry mediator; tumor necrosis factor receptor superfamily, mem ......
Chromosomal Location1p36.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TNFRSF14 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.