The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pat... See more...

Aliases for TNFSF12 Gene

Aliases for TNFSF12 Gene

  • TNF Superfamily Member 12 2 3 5
  • Tumor Necrosis Factor (Ligand) Superfamily, Member 12 2 3
  • Tumor Necrosis Factor Ligand Superfamily Member 12 3 4
  • APO3 Ligand 3 4
  • APO3L 3 4
  • DR3LG 3 4
  • TWEAK 3 4
  • Tumor Necrosis Factor Superfamily Member 12 3
  • TNF-Related WEAK Inducer Of Apoptosis 3
  • TNF-Related Weak Inducer Of Apoptosis 4
  • Tumor Necrosis Factor Ligand 4A 3
  • APO3/DR3 Ligand 3
  • TNLG4A 3

External Ids for TNFSF12 Gene

Previous GeneCards Identifiers for TNFSF12 Gene

  • GC17P007866
  • GC17P008192
  • GC17P007395
  • GC17P007652
  • GC17P007394
  • GC17P007401
  • GC17P007452
  • GC17P007346
  • GC17P007550
  • GC17P007553
  • GC17P007796
  • GC17P007829
  • GC17P007863
  • GC17P007560
  • GC17P007618
  • GC17P007675
  • GC17P007711
  • GC17P007740
  • GC17P007773

Summaries for TNFSF12 Gene

Entrez Gene Summary for TNFSF12 Gene

  • The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

GeneCards Summary for TNFSF12 Gene

TNFSF12 (TNF Superfamily Member 12) is a Protein Coding gene. Diseases associated with TNFSF12 include Common Variable Immunodeficiency and Peripheral Artery Disease. Among its related pathways are ERK Signaling and CDK-mediated phosphorylation and removal of Cdc6. 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 TNFSF12-TNFSF13.

UniProtKB/Swiss-Prot Summary for TNFSF12 Gene

  • Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines. Promotes IL8 secretion.

Gene Wiki entry for TNFSF12 Gene

Additional gene information for TNFSF12 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFSF12 Gene

Genomics for TNFSF12 Gene

GeneHancer (GH) Regulatory Elements for TNFSF12 Gene

Promoters and enhancers for TNFSF12 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 TNFSF12 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNFSF12

Top Transcription factor binding sites by QIAGEN in the TNFSF12 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • FOXO1a
  • MyoD
  • NF-kappaB
  • NF-kappaB1

Genomic Locations for TNFSF12 Gene

Genomic Locations for TNFSF12 Gene
chr17:7,549,058-7,557,890
(GRCh38/hg38)
Size:
8,833 bases
Orientation:
Plus strand
chr17:7,452,208-7,464,925
(GRCh37/hg19)
Size:
12,718 bases
Orientation:
Plus strand

Genomic View for TNFSF12 Gene

Genes around TNFSF12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFSF12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFSF12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFSF12 Gene

Proteins for TNFSF12 Gene

  • Protein details for TNFSF12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43508-TNF12_HUMAN
    Recommended name:
    Tumor necrosis factor ligand superfamily member 12
    Protein Accession:
    O43508
    Secondary Accessions:
    • Q8IZK7
    • Q8WUZ7

    Protein attributes for TNFSF12 Gene

    Size:
    249 amino acids
    Molecular mass:
    27216 Da
    Quaternary structure:
    • Homotrimer (Probable). Interacts with the angiogenic factor AGGF1/VG5Q.
    Miscellaneous:
    • [Isoform TWE-PRIL]: Based on a readthrough transcript which may produce a TWE-PRIL (TNFSF12-TNFSF13) fusion protein. Expressed at protein level in primary T-lymphocytes and monocytic cell lines.
    SequenceCaution:
    • Sequence=AAH19047.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TNFSF12 Gene

    Alternative splice isoforms for TNFSF12 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TNFSF12 Gene

Post-translational modifications for TNFSF12 Gene

  • The soluble form derives from the membrane form by proteolytic processing.
  • Glycosylation at Asn139
  • Modification sites at PhosphoSitePlus

Other Protein References for TNFSF12 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for TNFSF12
  • Santa Cruz Biotechnology (SCBT) Antibodies for TNFSF12

No data available for DME Specific Peptides for TNFSF12 Gene

Domains & Families for TNFSF12 Gene

Gene Families for TNFSF12 Gene

Protein Domains for TNFSF12 Gene

Blocks:
  • Tumor Necrosis Factor
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TNFSF12 Gene

GenScript: Design optimal peptide antigens:
  • Tumor necrosis factor (Ligand) superfamily, member 12 (Q4ACW9_HUMAN)
  • TNF-related weak inducer of apoptosis (TNF12_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43508

UniProtKB/Swiss-Prot:

TNF12_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 TNFSF12: view

Function for TNFSF12 Gene

Molecular function for TNFSF12 Gene

UniProtKB/Swiss-Prot Function:
Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines. Promotes IL8 secretion.
GENATLAS Biochemistry:
tumor necrosis factor (ligand) superfamily,member 12,abundantly expressed in many tissues,inducing IL8,weakly inducer of apoptosis

Phenotypes From GWAS Catalog for TNFSF12 Gene

Gene Ontology (GO) - Molecular Function for TNFSF12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS 9560343
GO:0005125 cytokine activity IEA --
GO:0005164 tumor necrosis factor receptor binding IEA --
GO:0005515 protein binding IPI,IEA 14961121
genes like me logo Genes that share ontologies with TNFSF12: view
genes like me logo Genes that share phenotypes with TNFSF12: view

Human Phenotype Ontology for TNFSF12 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TNFSF12 Gene

MGI Knock Outs for TNFSF12:

Animal Model Products

  • Taconic Biosciences Mouse Models for TNFSF12

CRISPR Products

miRNA for TNFSF12 Gene

miRTarBase miRNAs that target TNFSF12

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFSF12

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TNFSF12 Gene

Localization for TNFSF12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFSF12 Gene

Cell membrane; Single-pass type II membrane protein.
[Tumor necrosis factor ligand superfamily member 12, secreted form]: Secreted.
[Isoform TWE-PRIL]: Cell membrane; Single-pass 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 TNFSF12 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 2
mitochondrion 2
nucleus 2
cytosol 2
lysosome 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TNFSF12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 9560343
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with TNFSF12: view

Pathways & Interactions for TNFSF12 Gene

PathCards logo

SuperPathways for TNFSF12 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.47
.46
2 TNFR1 Pathway
.87
.87
.42
3 Apoptosis Modulation and Signaling
.35
4 Akt Signaling
.60
.60
.55
5 ERK Signaling
.61
.61
.51
genes like me logo Genes that share pathways with TNFSF12: view

Pathways by source for TNFSF12 Gene

2 GeneGo (Thomson Reuters) pathways for TNFSF12 Gene
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway
  • Apoptosis and survival Apoptotic TNF-family pathways
1 R&D Systems pathway for TNFSF12 Gene
21 Qiagen pathways for TNFSF12 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Apoptosis through Death Receptors
  • Cellular Apoptosis Pathway
2 Cell Signaling Technology pathways for TNFSF12 Gene

Gene Ontology (GO) - Biological Process for TNFSF12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0001938 positive regulation of endothelial cell proliferation TAS 14961121
GO:0006915 apoptotic process TAS 9560343
GO:0006955 immune response IEA --
GO:0007165 signal transduction TAS 9560343
genes like me logo Genes that share ontologies with TNFSF12: view

No data available for SIGNOR curated interactions for TNFSF12 Gene

Drugs & Compounds for TNFSF12 Gene

No Compound Related Data Available

Transcripts for TNFSF12 Gene

mRNA/cDNA for TNFSF12 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
5 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 TNFSF12

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TNFSF12 Gene

No ASD Table

Relevant External Links for TNFSF12 Gene

GeneLoc Exon Structure for
TNFSF12

Expression for TNFSF12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNFSF12 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNFSF12

mRNA Expression by UniProt/SwissProt for TNFSF12 Gene:

O43508-TNF12_HUMAN
Tissue specificity: Highly expressed in adult heart, pancreas, skeletal muscle, brain, colon, small intestine, lung, ovary, prostate, spleen, lymph node, appendix and peripheral blood lymphocytes. Low expression in kidney, testis, liver, placenta, thymus and bone marrow. Also detected in fetal kidney, liver, lung and brain.

Evidence on tissue expression from TISSUES for TNFSF12 Gene

  • Kidney(2.5)
  • Muscle(2.5)
  • Heart(2.3)
  • Nervous system(2.1)
  • Intestine(2)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFSF12 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • head
  • hypothalamus
  • meninges
  • middle ear
  • neck
  • pituitary gland
  • sinus
  • skull
  • thyroid
Thorax:
  • bronchus
  • heart
  • lung
Abdomen:
  • adrenal gland
  • intestine
  • large intestine
  • liver
  • small intestine
  • spleen
  • stomach
Pelvis:
  • anus
  • rectum
  • uterus
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • lymph node
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with TNFSF12: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for TNFSF12 Gene

Orthologs for TNFSF12 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNFSF12 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TNFSF12 31 30
  • 100 (n)
ManyToMany
cow
(Bos Taurus)
Mammalia TNFSF12 30
  • 88.94 (n)
TNFSF13B 31
  • 10 (a)
ManyToMany
dog
(Canis familiaris)
Mammalia TNFSF12 31 30
  • 88.46 (n)
OneToMany
mouse
(Mus musculus)
Mammalia Tnfsf12 17 31 30
  • 88.35 (n)
BC096441 31
  • 68 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Tnfsf12 30
  • 88.22 (n)
oppossum
(Monodelphis domestica)
Mammalia TNFSF13 31
  • 48 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 23 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 33 (a)
OneToMany
zebrafish
(Danio rerio)
Actinopterygii tnfsf12 30
  • 49.34 (n)
tnfsf13 31
  • 33 (a)
OneToMany
Species where no ortholog for TNFSF12 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)
  • 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 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)

Evolution for TNFSF12 Gene

ENSEMBL:
Gene Tree for TNFSF12 (if available)
TreeFam:
Gene Tree for TNFSF12 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFSF12: view image

Paralogs for TNFSF12 Gene

Paralogs for TNFSF12 Gene

(1) SIMAP similar genes for TNFSF12 Gene using alignment to 2 proteins:

  • TNF12_HUMAN
  • C0H5Y4_HUMAN
genes like me logo Genes that share paralogs with TNFSF12: view

Variants for TNFSF12 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNFSF12 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
567668 Uncertain Significance: Common variable immunodeficiency 7,549,491(+) G/C MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
638913 Uncertain Significance: Common variable immunodeficiency 7,557,316(+) T/C MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT
640807 Uncertain Significance: Common variable immunodeficiency 7,556,847(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
649356 Uncertain Significance: Common variable immunodeficiency 7,557,273(+) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT
654786 Uncertain Significance: Common variable immunodeficiency 7,550,181(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT

Additional dbSNP identifiers (rs#s) for TNFSF12 Gene

Structural Variations from Database of Genomic Variants (DGV) for TNFSF12 Gene

Variant ID Type Subtype PubMed ID
esv2422288 CNV deletion 17116639
nsv457659 CNV loss 19166990
nsv523672 CNV loss 19592680
nsv574322 CNV loss 21841781

Variation tolerance for TNFSF12 Gene

Residual Variation Intolerance Score: 26% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFSF12 Gene

Human Gene Mutation Database (HGMD)
TNFSF12
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFSF12

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFSF12 Gene

Disorders for TNFSF12 Gene

MalaCards: The human disease database

(7) MalaCards diseases for TNFSF12 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
common variable immunodeficiency
  • acquired agammaglobulinemia
peripheral artery disease
  • peripheral arterial disease
amnestic disorder
  • amnesia
systemic lupus erythematosus
  • sle
fetal alcohol spectrum disorder
  • fetal alcohol syndrome
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TNFSF12

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 TNFSF12: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFSF12 Gene

Publications for TNFSF12 Gene

  1. Identification of a ligand for the death-domain-containing receptor Apo3. (PMID: 9560343) Marsters SA … Ashkenazi A (Current biology : CB 1998) 2 3 4 54
  2. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. (PMID: 9405449) Chicheportiche Y … Browning JL (The Journal of biological chemistry 1997) 2 3 4 54
  3. Full-length, membrane-anchored TWEAK can function as a juxtacrine signaling molecule and activate the NF-kappaB pathway. (PMID: 20385556) Brown SA … Winkles JA (The Journal of biological chemistry 2010) 3 23 54
  4. Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity. (PMID: 19773279) Hosgood HD … Lan Q (Occupational and environmental medicine 2009) 3 41 54
  5. Considering TWEAK as a target for therapy in renal and vascular injury. (PMID: 19482507) Ortiz A … Blanco-Colio LM (Cytokine & growth factor reviews 2009) 3 23 54

Products for TNFSF12 Gene

Sources for TNFSF12 Gene