The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This transmembrane cytokine is a bidirectional signal transducer that acts as a ligand for TNFRSF9/4-1BB, which is a costimulatory receptor molecule in T lymphocytes. This cytokine and its receptor are involved in the antigen presentation process and in the generation o... See more...

Aliases for TNFSF9 Gene

Aliases for TNFSF9 Gene

  • TNF Superfamily Member 9 2 3 5
  • Tumor Necrosis Factor (Ligand) Superfamily, Member 9 2 3
  • Tumor Necrosis Factor Ligand Superfamily Member 9 3 4
  • Homolog Of Mouse 4-1BB-L 2 3
  • Receptor 4-1BB Ligand 2 3
  • 4-1BB Ligand 3 4
  • 4-1BBL 3 4
  • Tumor Necrosis Factor Superfamily Member 9 3
  • Tumor Necrosis Factor Ligand 5A 3
  • 4-1BB-L 3
  • CD137L 3
  • TNLG5A 3

External Ids for TNFSF9 Gene

Previous GeneCards Identifiers for TNFSF9 Gene

  • GC19P006625
  • GC19P006471
  • GC19P006482
  • GC19P006293

Summaries for TNFSF9 Gene

Entrez Gene Summary for TNFSF9 Gene

  • The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This transmembrane cytokine is a bidirectional signal transducer that acts as a ligand for TNFRSF9/4-1BB, which is a costimulatory receptor molecule in T lymphocytes. This cytokine and its receptor are involved in the antigen presentation process and in the generation of cytotoxic T cells. The receptor TNFRSF9/4-1BB is absent from resting T lymphocytes but rapidly expressed upon antigenic stimulation. The ligand encoded by this gene, TNFSF9/4-1BBL, has been shown to reactivate anergic T lymphocytes in addition to promoting T lymphocyte proliferation. This cytokine has also been shown to be required for the optimal CD8 responses in CD8 T cells. This cytokine is expressed in carcinoma cell lines, and is thought to be involved in T cell-tumor cell interaction.[provided by RefSeq, Oct 2008]

GeneCards Summary for TNFSF9 Gene

TNFSF9 (TNF Superfamily Member 9) is a Protein Coding gene. Diseases associated with TNFSF9 include Mouth Disease and Cone-Rod Dystrophy 2. Among its related pathways are ERK Signaling and Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and tumor necrosis factor receptor binding.

UniProtKB/Swiss-Prot Summary for TNFSF9 Gene

  • Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages.

Additional gene information for TNFSF9 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFSF9 Gene

Genomics for TNFSF9 Gene

GeneHancer (GH) Regulatory Elements for TNFSF9 Gene

Promoters and enhancers for TNFSF9 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
GH19J006527 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +2.6 2572 7.1 ZBTB40 EP300 NRF1 ZNF300 USF1 POLR2G SP1 BCLAF1 RBAK GTF2E2 TNFSF9 lnc-TUBB4A-2 SAFB2 ZNF557 KHSRP DUS3L SNRPEP4 ENSG00000267571 VMAC RANBP3
GH19J006575 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 8.3 +49.9 49885 5.5 RXRA ZBTB40 TCF12 SP1 JUND EP300 TRIM28 RELA MEF2C TRIM22 TNFSF14 TNFSF9 CD70 DENND1C ZNF557 piR-38129-054 piR-61945-242
GH19J006587 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 4.8 +59.2 59207 1.5 NRF1 SP1 EP300 ZBTB26 TRIM28 TRIM22 POLR2A TRIM25 MCM3 HDAC2 DUS3L ZNF557 VMAC DENND1C ARHGEF18 TRIP10 GPR108 CD70 TNFSF9 RPL7P50
GH19J006592 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 4.1 +64.0 64007 0.7 RELA MEF2C ATF2 ZNF384 ARNT MEF2B NBN IRF1 ZNF335 IKZF1 RPL7P50 lnc-TNFSF9-3 CD70 TNFSF9 DENND1C ZNF557 piR-61101-322
GH19J006517 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 3.7 -10.3 -10286 1.1 SP1 EP300 RELA RCOR1 TRIM22 POLR2A BCL11A ZNF316 MAFF SMC3 CD70 TNFSF9 RFX2 piR-46662-319
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNFSF9 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNFSF9

Top Transcription factor binding sites by QIAGEN in the TNFSF9 gene promoter:
  • NF-kappaB
  • NF-kappaB1
  • Sp1
  • TBP
  • TFIID

Genomic Locations for TNFSF9 Gene

Genomic Locations for TNFSF9 Gene
chr19:6,528,562-6,535,928
(GRCh38/hg38)
Size:
7,367 bases
Orientation:
Plus strand
chr19:6,531,010-6,535,939
(GRCh37/hg19)
Size:
4,930 bases
Orientation:
Plus strand

Genomic View for TNFSF9 Gene

Genes around TNFSF9 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFSF9 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFSF9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFSF9 Gene

Proteins for TNFSF9 Gene

  • Protein details for TNFSF9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P41273-TNFL9_HUMAN
    Recommended name:
    Tumor necrosis factor ligand superfamily member 9
    Protein Accession:
    P41273
    Secondary Accessions:
    • Q2M3S2

    Protein attributes for TNFSF9 Gene

    Size:
    254 amino acids
    Molecular mass:
    26625 Da
    Quaternary structure:
    • Homotrimer.

    Three dimensional structures from OCA and Proteopedia for TNFSF9 Gene

neXtProt entry for TNFSF9 Gene

Post-translational modifications for TNFSF9 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TNFSF9 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Boster Bio Antibodies for TNFSF9

Protein Products

  • Abcam proteins for TNFSF9

No data available for DME Specific Peptides for TNFSF9 Gene

Domains & Families for TNFSF9 Gene

Gene Families for TNFSF9 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for TNFSF9 Gene

Blocks:
  • Tumor Necrosis Factor
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TNFSF9 Gene

GenScript: Design optimal peptide antigens:
  • 4-1BB ligand (TNFL9_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P41273

UniProtKB/Swiss-Prot:

TNFL9_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 TNFSF9: view

Function for TNFSF9 Gene

Molecular function for TNFSF9 Gene

UniProtKB/Swiss-Prot Function:
Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages.
GENATLAS Biochemistry:
,tumor necrosis factor (ligand) superfamily,member 9,inducible T cell antigen 4-1BB ligand

Phenotypes From GWAS Catalog for TNFSF9 Gene

Gene Ontology (GO) - Molecular Function for TNFSF9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS 8088337
GO:0005125 cytokine activity IEA --
GO:0005164 tumor necrosis factor receptor binding IEA --
GO:0005515 protein binding IEA --
GO:0032813 tumor necrosis factor receptor superfamily binding IBA 21873635
genes like me logo Genes that share ontologies with TNFSF9: view
genes like me logo Genes that share phenotypes with TNFSF9: view

Animal Model Products

CRISPR Products

miRNA for TNFSF9 Gene

miRTarBase miRNAs that target TNFSF9

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for TNFSF9 Gene

Localization for TNFSF9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFSF9 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 TNFSF9 gene
Compartment Confidence
plasma membrane 4
extracellular 4
nucleus 2
cytosol 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TNFSF9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IEA --
GO:0005886 plasma membrane TAS,IBA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TNFSF9: view

Pathways & Interactions for TNFSF9 Gene

PathCards logo

SuperPathways for TNFSF9 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.47
.46
2 ERK Signaling
.61
.61
.51
3 Akt Signaling
.60
.60
4 PAK Pathway
.56
.56
5 T Cell Co-Signaling Pathway: Ligand-Receptor Interactions
genes like me logo Genes that share pathways with TNFSF9: view

Pathways by source for TNFSF9 Gene

1 R&D Systems pathway for TNFSF9 Gene
17 Qiagen pathways for TNFSF9 Gene
  • 4-1BB Pathway
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Endothelin-1 Signaling Pathway

Gene Ontology (GO) - Biological Process for TNFSF9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006955 immune response IEA --
GO:0007165 signal transduction IEA --
GO:0007267 cell-cell signaling TAS 8088337
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS --
GO:0042104 positive regulation of activated T cell proliferation IBA 21873635
genes like me logo Genes that share ontologies with TNFSF9: view

No data available for SIGNOR curated interactions for TNFSF9 Gene

Transcripts for TNFSF9 Gene

mRNA/cDNA for TNFSF9 Gene

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

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TNFSF9 Gene

No ASD Table

Relevant External Links for TNFSF9 Gene

GeneLoc Exon Structure for
TNFSF9

Expression for TNFSF9 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNFSF9 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TNFSF9 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNFSF9

SOURCE GeneReport for Unigene cluster for TNFSF9 Gene:

Hs.1524

mRNA Expression by UniProt/SwissProt for TNFSF9 Gene:

P41273-TNFL9_HUMAN
Tissue specificity: Expressed in brain, placenta, lung, skeletal muscle and kidney.

Evidence on tissue expression from TISSUES for TNFSF9 Gene

  • Lung(4.2)
  • Blood(2.5)
  • Spleen(2.2)
  • Lymph node(2.1)
genes like me logo Genes that share expression patterns with TNFSF9: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFSF9 Gene

Orthologs for TNFSF9 Gene

This gene was present in the common ancestor of mammals.

Orthologs for TNFSF9 Gene

Organism Taxonomy Gene Similarity Type Details
dog
(Canis familiaris)
Mammalia TNFSF9 31 30
  • 69.92 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TNFSF9 31 30
  • 63.62 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TNFSF9 31
  • 35 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TNFSF9 31
  • 34 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tnfsf9 31
  • 27 (a)
OneToOne
Species where no ortholog for TNFSF9 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • chimpanzee (Pan troglodytes)
  • 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)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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 TNFSF9 Gene

ENSEMBL:
Gene Tree for TNFSF9 (if available)
TreeFam:
Gene Tree for TNFSF9 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFSF9: view image

Paralogs for TNFSF9 Gene

No data available for Paralogs for TNFSF9 Gene

Variants for TNFSF9 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNFSF9 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
716716 Likely Benign: not provided 6,534,717(+) G/C MISSENSE_VARIANT
rs442511 - p.Pro17Ala

Additional dbSNP identifiers (rs#s) for TNFSF9 Gene

Structural Variations from Database of Genomic Variants (DGV) for TNFSF9 Gene

Variant ID Type Subtype PubMed ID
dgv1700n106 CNV deletion 24896259
esv22875 CNV loss 19812545
esv2668569 CNV deletion 23128226
nsv1072314 CNV deletion 25765185
nsv138022 CNV insertion 16902084
nsv833727 CNV loss 17160897
nsv833728 CNV loss 17160897

Variation tolerance for TNFSF9 Gene

Residual Variation Intolerance Score: 71.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.31; 41.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFSF9 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFSF9

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFSF9 Gene

Disorders for TNFSF9 Gene

MalaCards: The human disease database

(3) MalaCards diseases for TNFSF9 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
mouth disease
  • mouth disorders
cone-rod dystrophy 2
  • cord2
mast cell neoplasm
  • mast cell proliferative disease
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TNFSF9

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TNFSF9: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFSF9 Gene

Publications for TNFSF9 Gene

  1. The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily. (PMID: 20032458) Won EY … Cho HS (The Journal of biological chemistry 2010) 3 4 23 54
  2. Molecular and biological characterization of human 4-1BB and its ligand. (PMID: 8088337) Alderson MR … Din WS (European journal of immunology 1994) 2 3 4 54
  3. Risk of meningioma and common variation in genes related to innate immunity. (PMID: 20406964) Rajaraman P … Inskip PD (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2010) 3 41 54
  4. Polymorphisms in innate immunity genes and risk of childhood leukemia. (PMID: 20438785) Han S … Kang D (Human immunology 2010) 3 41 54
  5. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot". (PMID: 20628624) Johnatty SE … Australian Cancer Study (Ovarian Cancer) (PLoS genetics 2010) 3 41 54

Products for TNFSF9 Gene

  • Boster Bio Antibodies for TNFSF9
  • Boster Bio ELISA Kits for TNFSF9

Sources for TNFSF9 Gene