The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to in... See more...

Aliases for TNFSF14 Gene

Aliases for TNFSF14 Gene

  • TNF Superfamily Member 14 2 3 5
  • LIGHT 2 3 4
  • Tumor Necrosis Factor (Ligand) Superfamily, Member 14 2 3
  • Tumor Necrosis Factor Ligand Superfamily Member 14 3 4
  • Herpesvirus Entry Mediator Ligand 3 4
  • HVEM-L 2 4
  • CD258 2 3
  • HVEML 3 4
  • LTg 2 3
  • Tumor Necrosis Factor Superfamily Member 14 3
  • Herpes Virus Entry Mediator Ligand 4
  • Tumor Necrosis Factor Ligand 1D 3
  • CD258 Antigen 4
  • TNFSF14 5

External Ids for TNFSF14 Gene

Previous GeneCards Identifiers for TNFSF14 Gene

  • GC19M006759
  • GC19M006604
  • GC19M006615
  • GC19M006425

Summaries for TNFSF14 Gene

Entrez Gene Summary for TNFSF14 Gene

  • The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

GeneCards Summary for TNFSF14 Gene

TNFSF14 (TNF Superfamily Member 14) is a Protein Coding gene. Diseases associated with TNFSF14 include Herpes Simplex and Cone-Rod Dystrophy 2. Among its related pathways are PEDF Induced Signaling and LT-BetaR Pathway. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and tumor necrosis factor receptor binding. An important paralog of this gene is FASLG.

UniProtKB/Swiss-Prot Summary for TNFSF14 Gene

  • Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Acts as a ligand for TNFRSF14/HVEM (PubMed:9462508, PubMed:10754304). Upon binding to TNFRSF14/HVEM, delivers costimulatory signals to T cells, leading to T cell proliferation and IFNG production (PubMed:10754304).

Gene Wiki entry for TNFSF14 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFSF14 Gene

Genomics for TNFSF14 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TNFSF14 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J006667 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 607.1 +1.6 1594 4 HNRNPL POLR2A BACH1 LARP7 ZNF143 RELA RBFOX2 SMAD5 NR2C1 ZNF24 TNFSF14 piR-57460-334 ZNF557 XAB2 DUS3L KHSRP ACSBG2 ENSG00000267571 VMAC GTF2F1
GH19J006674 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 51.4 -4.5 -4512 1.1 SP1 ZNF512 BACH1 JUND LARP7 MTA2 ZNF143 RELA RBFOX2 PKNOX1 piR-57460-335 TNFSF14 DENND1C C3 TRIP10 GPR108 XAB2 ZNF557 DUS3L KHSRP
GH19J006639 Enhancer 1.1 FANTOM5 ENCODE dbSUPER 21.9 +31.0 31037 0.7 ZNF629 JUND PKNOX1 HDAC1 EED MGA RUNX3 NFE2 HDAC2 ZNF316 lnc-TRIP10-5 TNFSF14 GTF2F1 TNFSF9 piR-57460-333 CD70
GH19J006717 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 12.9 -50.6 -50587 6.4 HNRNPL GATAD2A PRDM10 REST TFE3 SOX13 IKZF1 NFKBIZ RCOR2 BACH1 HSALNG0123587 C3 DUS3L ZNF557 GPR108 XAB2 ENSG00000267571 VMAC TNFSF14 KHSRP
GH19J006575 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 12.2 +92.1 92148 5.5 SP1 ZNF512 IKZF1 KDM1A POLR2A BACH1 JUND RELA PKNOX1 TCF12 TNFSF14 TNFSF9 CD70 DENND1C ZNF557 piR-38129-054 piR-61945-242
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNFSF14 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNFSF14

Top Transcription factor binding sites by QIAGEN in the TNFSF14 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • STAT3

Genomic Locations for TNFSF14 Gene

Genomic Locations for TNFSF14 Gene
chr19:6,658,126-6,670,595
(GRCh38/hg38)
Size:
12,470 bases
Orientation:
Minus strand
chr19:6,663,148-6,670,599
(GRCh37/hg19)
Size:
7,452 bases
Orientation:
Minus strand

Genomic View for TNFSF14 Gene

Genes around TNFSF14 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFSF14 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFSF14 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFSF14 Gene

Proteins for TNFSF14 Gene

  • Protein details for TNFSF14 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43557-TNF14_HUMAN
    Recommended name:
    Tumor necrosis factor ligand superfamily member 14
    Protein Accession:
    O43557
    Secondary Accessions:
    • A8K7M2
    • C9J5H4
    • O75476
    • Q6FHA1
    • Q8WVF8
    • Q96LD2

    Protein attributes for TNFSF14 Gene

    Size:
    240 amino acids
    Molecular mass:
    26350 Da
    Quaternary structure:
    • Homotrimer. Interacts with TNFRSF14.

    Three dimensional structures from OCA and Proteopedia for TNFSF14 Gene

    Alternative splice isoforms for TNFSF14 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TNFSF14 Gene

Post-translational modifications for TNFSF14 Gene

Other Protein References for TNFSF14 Gene

Antibody Products

  • Abcam antibodies for TNFSF14
  • Santa Cruz Biotechnology (SCBT) Antibodies for TNFSF14

No data available for DME Specific Peptides for TNFSF14 Gene

Domains & Families for TNFSF14 Gene

Gene Families for TNFSF14 Gene

HGNC:
Human Protein Atlas (HPA):
  • CD markers
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for TNFSF14 Gene

InterPro:
Blocks:
  • Tumor Necrosis Factor
  • Tumour necrosis factor family signature
ProtoNet:

Suggested Antigen Peptide Sequences for TNFSF14 Gene

GenScript: Design optimal peptide antigens:
  • Herpes virus entry mediator ligand (TNF14_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43557

UniProtKB/Swiss-Prot:

TNF14_HUMAN :
  • Belongs to the tumor necrosis factor family.
Family:
  • Belongs to the tumor necrosis factor family.
genes like me logo Genes that share domains with TNFSF14: view

Function for TNFSF14 Gene

Molecular function for TNFSF14 Gene

UniProtKB/Swiss-Prot Function:
Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Acts as a ligand for TNFRSF14/HVEM (PubMed:9462508, PubMed:10754304). Upon binding to TNFRSF14/HVEM, delivers costimulatory signals to T cells, leading to T cell proliferation and IFNG production (PubMed:10754304).
UniProtKB/Swiss-Prot Induction:
Up-regulated after T-cell activation.
GENATLAS Biochemistry:
tumor necrosis factor (ligand) superfamily,member 14,highly expressed in splenocytes,activated PBL,CD8+ tumor infiltrating lymphocytes,granulocytes,monocytes,inducing apoptosis

Phenotypes From GWAS Catalog for TNFSF14 Gene

Gene Ontology (GO) - Molecular Function for TNFSF14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS,IPI 12393901
GO:0005125 cytokine activity IEA --
GO:0005164 tumor necrosis factor receptor binding IEA --
GO:0005515 protein binding IPI 9462508
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process IDA 12393901
genes like me logo Genes that share ontologies with TNFSF14: view
genes like me logo Genes that share phenotypes with TNFSF14: view

Animal Models for TNFSF14 Gene

MGI Knock Outs for TNFSF14:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFSF14

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TNFSF14 Gene

Localization for TNFSF14 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFSF14 Gene

[Tumor necrosis factor ligand superfamily member 14, membrane form]: Cell membrane. Single-pass type II membrane protein.
[Tumor necrosis factor ligand superfamily member 14, soluble form]: Secreted.
[Isoform 2]: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TNFSF14 gene
Compartment Confidence
plasma membrane 5
extracellular 5
mitochondrion 2
nucleus 2
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TNFSF14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA --
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with TNFSF14: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TNFSF14 Gene

Pathways & Interactions for TNFSF14 Gene

PathCards logo

SuperPathways for TNFSF14 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.47
.46
2 ERK Signaling
.61
.61
.51
3 TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions
4 Akt Signaling
.60
.60
5 PAK Pathway
.56
.56
genes like me logo Genes that share pathways with TNFSF14: view

Pathways by source for TNFSF14 Gene

2 GeneGo (Thomson Reuters) pathways for TNFSF14 Gene
  • Apoptosis and survival Apoptotic TNF-family pathways
  • Apoptosis and survival Lymphotoxin-beta receptor signaling
17 Qiagen pathways for TNFSF14 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Endothelin-1 Signaling Pathway
  • ERK Signaling

SIGNOR curated interactions for TNFSF14 Gene

Activates:

Gene Ontology (GO) - Biological Process for TNFSF14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process TAS 10799510
GO:0006955 immune response IEA --
GO:0007165 signal transduction TAS,NAS 12393901
GO:0010820 positive regulation of T cell chemotaxis IEA --
GO:0031295 T cell costimulation IDA 10754304
genes like me logo Genes that share ontologies with TNFSF14: view

Drugs & Compounds for TNFSF14 Gene

(1) Drugs for TNFSF14 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Baminercept Investigational Pharma 0

(1) Additional Compounds for TNFSF14 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TNFSF14: view

Transcripts for TNFSF14 Gene

mRNA/cDNA for TNFSF14 Gene

3 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFSF14

Alternative Splicing Database (ASD) splice patterns (SP) for TNFSF14 Gene

No ASD Table

Relevant External Links for TNFSF14 Gene

GeneLoc Exon Structure for
TNFSF14

Expression for TNFSF14 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNFSF14 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TNFSF14 Gene

This gene is overexpressed in Liver (x19.4) and Whole Blood (x11.9).

Protein differential expression in normal tissues from HIPED for TNFSF14 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (51.0), CD8 Tcells (7.3), and NK cells (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TNFSF14 Gene



Protein tissue co-expression partners for TNFSF14 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNFSF14

SOURCE GeneReport for Unigene cluster for TNFSF14 Gene:

Hs.129708

mRNA Expression by UniProt/SwissProt for TNFSF14 Gene:

O43557-TNF14_HUMAN
Tissue specificity: Predominantly expressed in the spleen but also found in the brain. Weakly expressed in peripheral lymphoid tissues and in heart, placenta, liver, lung, appendix, and kidney, and no expression seen in fetal tissues, endocrine glands, or nonhematopoietic tumor lines.

Evidence on tissue expression from TISSUES for TNFSF14 Gene

  • Spleen(4.5)
  • Liver(4.4)
  • Blood(2.6)
  • Intestine(2.4)
  • Bone marrow(2.3)
  • Lymph node(2.3)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with TNFSF14: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFSF14 Gene

Orthologs for TNFSF14 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNFSF14 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TNFSF14 30 31
  • 98.61 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TNFSF14 30 31
  • 82.91 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TNFSF14 30 31
  • 78.86 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tnfsf14 30
  • 77.54 (n)
Mouse
(Mus musculus)
Mammalia Tnfsf14 30 17 31
  • 76.98 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TNFSF14 31
  • 66 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TNFSF14 31
  • 52 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TNFSF14 31
  • 42 (a)
OneToOne
Species where no ortholog for TNFSF14 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for TNFSF14 Gene

ENSEMBL:
Gene Tree for TNFSF14 (if available)
TreeFam:
Gene Tree for TNFSF14 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFSF14: view image

Paralogs for TNFSF14 Gene

Paralogs for TNFSF14 Gene

genes like me logo Genes that share paralogs with TNFSF14: view

Variants for TNFSF14 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNFSF14 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
740464 Benign: not provided 6,665,046(-) G/A SYNONYMOUS_VARIANT
746620 Benign: not provided 6,670,013(-) G/A SYNONYMOUS_VARIANT
777388 Benign: not provided 6,664,944(-) G/A SYNONYMOUS_VARIANT
rs17851606 - p.Leu120Val
rs2291667 - p.Ser32Leu

Additional dbSNP identifiers (rs#s) for TNFSF14 Gene

Structural Variations from Database of Genomic Variants (DGV) for TNFSF14 Gene

Variant ID Type Subtype PubMed ID
nsv1134749 CNV deletion 24896259
nsv833728 CNV loss 17160897

Variation tolerance for TNFSF14 Gene

Residual Variation Intolerance Score: 61.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.56; 12.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFSF14 Gene

Human Gene Mutation Database (HGMD)
TNFSF14
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFSF14

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFSF14 Gene

Disorders for TNFSF14 Gene

MalaCards: The human disease database

(2) MalaCards diseases for TNFSF14 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
herpes simplex
  • herpesvirus hominis disease
cone-rod dystrophy 2
  • cord2
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TNFSF14

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TNFSF14: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFSF14 Gene

Publications for TNFSF14 Gene

  1. Genomic characterization of LIGHT reveals linkage to an immune response locus on chromosome 19p13.3 and distinct isoforms generated by alternate splicing or proteolysis. (PMID: 11673523) Granger SW … Ware CF (Journal of immunology (Baltimore, Md. : 1950) 2001) 3 4 23
  2. LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. (PMID: 9462508) Mauri DN … Ware CF (Immunity 1998) 2 3 4
  3. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. (PMID: 21833088) International Multiple Sclerosis Genetics Consortium … Compston A (Nature 2011) 3 41
  4. CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis. (PMID: 20096889) Ogawa T … Nishizawa O (The Journal of urology 2010) 3 23
  5. An approach based on a genome-wide association study reveals candidate loci for narcolepsy. (PMID: 20677014) Shimada M … Tokunaga K (Human genetics 2010) 3 41

Products for TNFSF14 Gene

Sources for TNFSF14 Gene