TNFSF15 Gene

HGNC Family Tumor necrosis factor (ligand) superfamily (TNFSF)
Name tumor necrosis factor (ligand) superfamily, member 15
Description The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
Summary
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Genetic association studies in diverse populations have implicated variations in TNFSF15 in susceptibility to inflammatory bowel disease (IBD)—including Crohn’s disease and ulcerative colitis—as well as in other immune‐mediated conditions such as primary biliary cirrhosis and even leprosy, underscoring its central role in modulating host–pathogen interactions and autoimmunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUpon receptor engagement, TNFSF15 triggers intracellular signaling cascades—most notably activation of NF‐κB and MAP kinase pathways—that balance cell survival and apoptosis. This signaling underlies its capacity to enhance T‐cell proliferation, cytokine secretion, and the differentiation of specialized effector subsets. Upregulation of TNFSF15 and its receptor components in inflamed tissues (for example, in the synovium of rheumatoid arthritis patients) further supports its role in amplifying chronic inflammatory responses and mediating immune cell activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its immune‐modulatory effects, TNFSF15 influences vascular homeostasis and atherogenesis. Certain isoforms (such as VEGI‐192) display potent antiangiogenic activity, thereby impeding endothelial cell proliferation and neovascularization; this property has been linked with reduced tumor growth and progression. Moreover, TNFSF15 modulates macrophage functions by enhancing lipoprotein uptake and altering cholesterol efflux, processes that contribute to foam cell formation and plaque instability in atherosclerosis. Its induction downstream of microbial products further implicates TNFSF15 in bridging innate immune recognition with vascular inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have further expanded the spectrum of TNFSF15’s functions to include regulation of innate lymphoid cell activity and modulation of responses in extraintestinal tissues. Its expression is altered in a range of inflammatory settings—including psoriasis, renal injury, and other autoimmune conditions—whereby it contributes not only to local cytokine networks but also to tissue remodeling and apoptosis. 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Synonyms TL1A, TL1, VEGI, VEGI192A, TNLG1B
Proteins TNF15_HUMAN
NCBI Gene ID 9966
API
Download Associations
Predicted Functions View TNFSF15's ARCHS4 Predicted Functions.
Co-expressed Genes View TNFSF15's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View TNFSF15's ARCHS4 Predicted Functions.

Functional Associations

TNFSF15 has 6,314 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 106 datasets.

Click the + buttons to view associations for TNFSF15 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Achilles Cell Line Gene Essentiality Profiles cell lines with fitness changed by TNFSF15 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of TNFSF15 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of TNFSF15 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of TNFSF15 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of TNFSF15 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of TNFSF15 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TNFSF15 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TNFSF15 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of TNFSF15 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of TNFSF15 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of TNFSF15 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with TNFSF15 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of TNFSF15 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of TNFSF15 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of TNFSF15 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of TNFSF15 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing TNFSF15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing TNFSF15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with TNFSF15 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with TNFSF15 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of TNFSF15 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with TNFSF15 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with TNFSF15 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with TNFSF15 gene/protein from the curated CTD Gene-Disease Associations dataset.
dbGAP Gene-Trait Associations traits associated with TNFSF15 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by TNFSF15 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores diseases associated with TNFSF15 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with TNFSF15 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with TNFSF15 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with TNFSF15 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with TNFSF15 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with TNFSF15 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at TNFSF15 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of TNFSF15 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of TNFSF15 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing TNFSF15 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with TNFSF15 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with TNFSF15 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of TNFSF15 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with TNFSF15 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing TNFSF15 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of TNFSF15 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of TNFSF15 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of TNFSF15 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of TNFSF15 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of TNFSF15 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of TNFSF15 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving TNFSF15 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving TNFSF15 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving TNFSF15 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing TNFSF15 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by TNFSF15 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by TNFSF15 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of TNFSF15 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of TNFSF15 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of TNFSF15 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with TNFSF15 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with TNFSF15 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Disease Associations diseases associated with TNFSF15 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with TNFSF15 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of TNFSF15 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of TNFSF15 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of TNFSF15 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of TNFSF15 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of TNFSF15 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with TNFSF15 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for TNFSF15 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of TNFSF15 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of TNFSF15 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of TNFSF15 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEGG Pathways pathways involving TNFSF15 protein from the KEGG Pathways dataset.
KEGG Pathways 2026 pathways involving TNFSF15 protein from the KEGG Pathways 2026 dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of TNFSF15 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with TNFSF15 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of TNFSF15 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of TNFSF15 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of TNFSF15 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain TNFSF15 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by TNFSF15 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting TNFSF15 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of TNFSF15 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by TNFSF15 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of TNFSF15 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of TNFSF15 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for TNFSF15 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of TNFSF15 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of TNFSF15 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving TNFSF15 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving TNFSF15 protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving TNFSF15 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at TNFSF15 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of TNFSF15 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of TNFSF15 gene from the RummaGEO Gene Perturbation Signatures dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of TNFSF15 gene from the Sci-Plex Drug Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of TNFSF15 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of TNFSF15 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of TNFSF15 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of TNFSF15 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of TNFSF15 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of TNFSF15 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of TNFSF15 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of TNFSF15 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with TNFSF15 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with TNFSF15 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving TNFSF15 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving TNFSF15 protein from the WikiPathways Pathways 2024 dataset.