This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transc... See more...

Aliases for TNFSF4 Gene

Aliases for TNFSF4 Gene

  • TNF Superfamily Member 4 2 3 5
  • Tumor Necrosis Factor Ligand Superfamily Member 4 3 4
  • Glycoprotein Gp34 3 4
  • OX-40L 2 3
  • CD252 2 3
  • TXGP1 3 4
  • Tax-Transcriptionally Activated Glycoprotein 1 (34kD) 3
  • Tax-Transcriptionally Activated Glycoprotein 1, 34kD 2
  • Tumor Necrosis Factor (Ligand) Superfamily, Member 4 2
  • Tumor Necrosis Factor (Ligand) Superfamily Member 4 3
  • TAX Transcriptionally-Activated Glycoprotein 1 4
  • Tumor Necrosis Factor Superfamily Member 4 3
  • Tumor Necrosis Factor Ligand 2B 3
  • OX40 Antigen Ligand 3
  • CD252 Antigen 4
  • CD134 Ligand 3
  • OX40 Ligand 4
  • CD134L 3
  • TNLG2B 3
  • TNFSF4 5
  • OX4OL 3
  • OX40L 4
  • GP34 3
  • Gp34 2

External Ids for TNFSF4 Gene

Previous HGNC Symbols for TNFSF4 Gene

  • TXGP1

Previous GeneCards Identifiers for TNFSF4 Gene

  • GC01M170716
  • GC01M168781
  • GC01M169733
  • GC01M170392
  • GC01M169884
  • GC01M171419
  • GC01M173152
  • GC01M144377

Summaries for TNFSF4 Gene

Entrez Gene Summary for TNFSF4 Gene

  • This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneCards Summary for TNFSF4 Gene

TNFSF4 (TNF Superfamily Member 4) is a Protein Coding gene. Diseases associated with TNFSF4 include Myocardial Infarction and Systemic Lupus Erythematosus. Among its related pathways are PEDF Induced Signaling and TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and tumor necrosis factor receptor binding.

UniProtKB/Swiss-Prot Summary for TNFSF4 Gene

  • Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFSF4 Gene

Genomics for TNFSF4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TNFSF4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNFSF4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNFSF4

Top Transcription factor binding sites by QIAGEN in the TNFSF4 gene promoter:
  • aMEF-2
  • AML1a
  • AP-1
  • ATF-2
  • c-Jun
  • C/EBPalpha
  • MEF-2
  • MEF-2A
  • POU3F2
  • POU6F1 (c2)

Genomic Locations for TNFSF4 Gene

Genomic Locations for TNFSF4 Gene
chr1:173,183,729-173,462,208
(GRCh38/hg38)
Size:
278,480 bases
Orientation:
Minus strand
chr1:173,152,870-173,176,471
(GRCh37/hg19)
Size:
23,602 bases
Orientation:
Minus strand

Genomic View for TNFSF4 Gene

Genes around TNFSF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFSF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFSF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFSF4 Gene

Proteins for TNFSF4 Gene

  • Protein details for TNFSF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P23510-TNFL4_HUMAN
    Recommended name:
    Tumor necrosis factor ligand superfamily member 4
    Protein Accession:
    P23510
    Secondary Accessions:
    • Q5JZA5
    • Q8IV74
    • Q9HCN9

    Protein attributes for TNFSF4 Gene

    Size:
    183 amino acids
    Molecular mass:
    21050 Da
    Quaternary structure:
    • Homotrimer.

    Three dimensional structures from OCA and Proteopedia for TNFSF4 Gene

    Alternative splice isoforms for TNFSF4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TNFSF4 Gene

Post-translational modifications for TNFSF4 Gene

  • Glycosylation at Asn90, Asn114, Asn152, and Asn157
  • Modification sites at PhosphoSitePlus

Other Protein References for TNFSF4 Gene

Antibody Products

  • Abcam antibodies for TNFSF4

No data available for DME Specific Peptides for TNFSF4 Gene

Domains & Families for TNFSF4 Gene

Gene Families for TNFSF4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • CD markers
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for TNFSF4 Gene

InterPro:
Blocks:
  • Tumor Necrosis Factor
ProtoNet:

Suggested Antigen Peptide Sequences for TNFSF4 Gene

GenScript: Design optimal peptide antigens:
  • TNFSF4 protein (Q6FGS4_HUMAN)
  • cDNA FLJ50815, highly similar to Tumor necrosis factor ligand superfamilymember 4 (Q8IV74_HUMAN)
  • TAX transcriptionally-activated glycoprotein 1 (TNFL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P23510

UniProtKB/Swiss-Prot:

TNFL4_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 TNFSF4: view

Function for TNFSF4 Gene

Molecular function for TNFSF4 Gene

UniProtKB/Swiss-Prot Function:
Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.
UniProtKB/Swiss-Prot Induction:
By HTLV-1 transactivator p40-Tax.
GENATLAS Biochemistry:
tumor necrosis factor (ligand) superfamily,member 4,tax-transcriptionally activated glycoprotein1,human OX-40 ligand,expressed in T cell infected by HTLV1

Phenotypes From GWAS Catalog for TNFSF4 Gene

Gene Ontology (GO) - Molecular Function for TNFSF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS 7913952
GO:0005125 cytokine activity IEA --
GO:0005164 tumor necrosis factor receptor binding IEA --
GO:0005515 protein binding IPI 16905106
GO:0032813 tumor necrosis factor receptor superfamily binding IBA,ISS --
genes like me logo Genes that share ontologies with TNFSF4: view
genes like me logo Genes that share phenotypes with TNFSF4: view

Human Phenotype Ontology for TNFSF4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TNFSF4 Gene

MGI Knock Outs for TNFSF4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFSF4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TNFSF4 Gene

Localization for TNFSF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFSF4 Gene

Membrane. Single-pass type II membrane protein.

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 TNFSF4 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 3
nucleus 2
endosome 2
lysosome 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TNFSF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IBA,IDA 17166734
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane NAS 18397322
GO:0009986 cell surface IDA 18397322
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with TNFSF4: view

Pathways & Interactions for TNFSF4 Gene

PathCards logo

SuperPathways for TNFSF4 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 TNFSF4: view

Pathways by source for TNFSF4 Gene

1 Sino Biological pathway for TNFSF4 Gene
1 BioSystems pathway for TNFSF4 Gene
1 KEGG pathway for TNFSF4 Gene
1 GeneGo (Thomson Reuters) pathway for TNFSF4 Gene
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway
17 Qiagen pathways for TNFSF4 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Endothelin-1 Signaling Pathway
  • ERK Signaling
1 Cell Signaling Technology pathway for TNFSF4 Gene

SIGNOR curated interactions for TNFSF4 Gene

Activates:

Gene Ontology (GO) - Biological Process for TNFSF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001819 positive regulation of cytokine production IBA 21873635
GO:0002215 defense response to nematode ISS --
GO:0002526 acute inflammatory response ISS --
GO:0002726 positive regulation of T cell cytokine production ISS --
GO:0002819 regulation of adaptive immune response ISS --
genes like me logo Genes that share ontologies with TNFSF4: view

Drugs & Compounds for TNFSF4 Gene

No Compound Related Data Available

Transcripts for TNFSF4 Gene

mRNA/cDNA for TNFSF4 Gene

2 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
3 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 TNFSF4

Alternative Splicing Database (ASD) splice patterns (SP) for TNFSF4 Gene

No ASD Table

Relevant External Links for TNFSF4 Gene

GeneLoc Exon Structure for
TNFSF4

Expression for TNFSF4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNFSF4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNFSF4

SOURCE GeneReport for Unigene cluster for TNFSF4 Gene:

Hs.181097

Evidence on tissue expression from TISSUES for TNFSF4 Gene

  • Intestine(3.6)
  • Liver(3.6)
  • Heart(3.5)
  • Nervous system(3.4)
  • Stomach(3.2)
  • Muscle(3.2)
  • Kidney(3.2)
  • Lymph node(3.1)
  • Spleen(3.1)
  • Blood(3)
  • Skin(2.7)
  • Bone marrow(2.5)
  • Lung(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFSF4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
  • mouth
  • pharynx
Thorax:
  • heart
General:
  • blood vessel
  • peripheral nervous system
genes like me logo Genes that share expression patterns with TNFSF4: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for TNFSF4 Gene

Orthologs for TNFSF4 Gene

This gene was present in the common ancestor of mammals.

Orthologs for TNFSF4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TNFSF4 30 31
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TNFSF4 30 31
  • 81.68 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TNFSF4 30 31
  • 81.4 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tnfsf4 30
  • 69.65 (n)
Mouse
(Mus musculus)
Mammalia Tnfsf4 30 17 31
  • 68.54 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TNFSF4 31
  • 36 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TNFSF4 31
  • 35 (a)
OneToOne
Species where no ortholog for TNFSF4 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)
  • Lizard (Anolis carolinensis)
  • 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 TNFSF4 Gene

ENSEMBL:
Gene Tree for TNFSF4 (if available)
TreeFam:
Gene Tree for TNFSF4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFSF4: view image

Paralogs for TNFSF4 Gene

No data available for Paralogs for TNFSF4 Gene

Variants for TNFSF4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNFSF4 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
747383 Likely Benign: not provided 173,186,590(-) G/A SYNONYMOUS_VARIANT
772822 Benign: not provided 173,188,537(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for TNFSF4 Gene

Variation tolerance for TNFSF4 Gene

Residual Variation Intolerance Score: 46.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.49; 10.75% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFSF4 Gene

Human Gene Mutation Database (HGMD)
TNFSF4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFSF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for TNFSF4 Gene

Disorders for TNFSF4 Gene

MalaCards: The human disease database

(12) MalaCards diseases for TNFSF4 Gene - From: OMIM, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
myocardial infarction
  • myocardial infarction, susceptibility to
systemic lupus erythematosus
  • sle
narcolepsy 1
  • nrclp1
lupus erythematosus
  • systemic lupus erythematosus
sjogren syndrome
  • sicca syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

TNFL4_HUMAN
  • Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269 PubMed:18059267}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The upstream region of TNFSF4 contains a single risk haplotype for SLE, which is correlated with increased expression of both cell-surface TNFSF4 and TNFSF4 transcripts. Increased levels of TNFSF4 are thought to augment T-cell-APC interaction and the functional consequences of T-cell activation, thereby destabilizing peripheral tolerance.

Additional Disease Information for TNFSF4

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 TNFSF4: view

No data available for Genatlas for TNFSF4 Gene

Publications for TNFSF4 Gene

  1. New variations in human OX40 ligand (CD134L) gene. (PMID: 11197696) Hikami K … Tokunaga K (Genes and immunity 2000) 3 4 23 41
  2. Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. (PMID: 8076595) Baum PR … Clifford KN (The EMBO journal 1994) 2 3 4 23
  3. Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. (PMID: 1996093) Miura S … Nakamura M (Molecular and cellular biology 1991) 2 3 4 23
  4. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. (PMID: 19778912) Gourh P … Agarwal SK (Annals of the rheumatic diseases 2010) 3 23 41
  5. Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus. (PMID: 19092840) Delgado-Vega AM … Alarcón-Riquelme ME (Genes and immunity 2009) 3 23 41

Products for TNFSF4 Gene

Sources for TNFSF4 Gene