The protein encoded by this gene is a secretory protein that contains a hyaluronan-binding domain, and thus is a member of the hyaluronan-binding protein family. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable complex with inter-alpha-inhibitor (I alpha I), and thus enhance ... See more...

Aliases for TNFAIP6 Gene

Aliases for TNFAIP6 Gene

  • TNF Alpha Induced Protein 6 2 3 5
  • TSG-6 2 3 4
  • TSG6 2 3 4
  • Tumor Necrosis Factor-Inducible Gene 6 Protein 3 4
  • TNF-Stimulated Gene 6 Protein 3 4
  • Hyaluronate-Binding Protein 3 4
  • Tumor Necrosis Factor Alpha-Inducible Protein 6 3
  • Tumor Necrosis Factor-Stimulated Gene-6 Protein 3
  • Tumor Necrosis Factor, Alpha-Induced Protein 6 2
  • Tumor Necrosis Factor, Alpha Induced Protein 6 3
  • Tumor Necrosis Factor Alpha-Induced Protein 6 4
  • TNF Alpha-Induced Protein 6 4
  • TNFAIP6 5

External Ids for TNFAIP6 Gene

Previous GeneCards Identifiers for TNFAIP6 Gene

  • GC02P149908
  • GC02P150743
  • GC02P152178
  • GC02P152416
  • GC02P152039
  • GC02P151922
  • GC02P144110

Summaries for TNFAIP6 Gene

Entrez Gene Summary for TNFAIP6 Gene

  • The protein encoded by this gene is a secretory protein that contains a hyaluronan-binding domain, and thus is a member of the hyaluronan-binding protein family. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable complex with inter-alpha-inhibitor (I alpha I), and thus enhance the serine protease inhibitory activity of I alpha I, which is important in the protease network associated with inflammation. This gene can be induced by proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-1. Enhanced levels of this protein are found in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis.[provided by RefSeq, Dec 2010]

GeneCards Summary for TNFAIP6 Gene

TNFAIP6 (TNF Alpha Induced Protein 6) is a Protein Coding gene. Diseases associated with TNFAIP6 include Arthritis and Rheumatoid Arthritis. Among its related pathways are Akt Signaling and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include hyaluronic acid binding. An important paralog of this gene is STAB1.

UniProtKB/Swiss-Prot Summary for TNFAIP6 Gene

  • Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis.

Gene Wiki entry for TNFAIP6 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFAIP6 Gene

Genomics for TNFAIP6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TNFAIP6 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
GH02J151356 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE CraniofacialAtlas 260.8 +0.9 919 3.4 CEBPB EP300 MAFF RFX5 ZNF316 TBP MAFK ZNF384 POLR2A ATF3 TNFAIP6 RBM43 piR-43106-125 LOC101929319 RIF1
GH02J151288 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 42.7 -68.0 -68048 3.9 BCLAF1 ZNF207 MYC IKZF1 ZNF592 POLR2A ATF3 NFIC ZIC2 YY1 NMI RBM43 HSALNG0019606 lnc-RBM43-3 TNFAIP6 RIF1 STAM2 RPL30P2
GH02J151260 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 39.7 -96.1 -96075 3 ZNF207 MYC ZNF600 IKZF1 ZNF592 KLF9 POLR2A CEBPA ZNF223 YY1 RBM43 HSALNG0019604 TNFAIP6 NMI lnc-RBM43-2 RND3
GH02J151355 Enhancer 0.2 Ensembl 260.4 -1.8 -1791 0.8 TNFAIP6 LOC101929319 piR-48950-096 NMI
GH02J151339 Promoter/Enhancer 0.7 EPDnew ENCODE 48.4 -18.1 -18052 0.8 IKZF1 ZSCAN4 POLR2A NMI TNFAIP6 piR-48950-096 LOC101929319
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNFAIP6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNFAIP6

Top Transcription factor binding sites by QIAGEN in the TNFAIP6 gene promoter:
  • Hlf
  • NF-kappaB
  • NF-kappaB1
  • NF-kappaB2
  • STAT1
  • STAT1alpha
  • STAT1beta
  • STAT2
  • STAT3
  • STAT4

Genomic Locations for TNFAIP6 Gene

Latest Assembly
chr2:151,357,592-151,380,046
(GRCh38/hg38)
Size:
22,455 bases
Orientation:
Plus strand

Previous Assembly
chr2:152,214,106-152,236,560
(GRCh37/hg19 by Entrez Gene)
Size:
22,455 bases
Orientation:
Plus strand

chr2:152,214,106-152,236,560
(GRCh37/hg19 by Ensembl)
Size:
22,455 bases
Orientation:
Plus strand

Genomic View for TNFAIP6 Gene

Genes around TNFAIP6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFAIP6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFAIP6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFAIP6 Gene

Proteins for TNFAIP6 Gene

  • Protein details for TNFAIP6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P98066-TSG6_HUMAN
    Recommended name:
    Tumor necrosis factor-inducible gene 6 protein
    Protein Accession:
    P98066
    Secondary Accessions:
    • Q53TI7
    • Q8WWI9

    Protein attributes for TNFAIP6 Gene

    Size:
    277 amino acids
    Molecular mass:
    31203 Da
    Quaternary structure:
    • Interacts with inter-alpha-inhibitor (I-alpha-I). Chondroitin sulfate may be required for the stability of the complex.

    Three dimensional structures from OCA and Proteopedia for TNFAIP6 Gene

neXtProt entry for TNFAIP6 Gene

Post-translational modifications for TNFAIP6 Gene

  • Glycosylation at Asn118 and Asn258
  • Modification sites at PhosphoSitePlus

Other Protein References for TNFAIP6 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TNFAIP6 Gene

Domains & Families for TNFAIP6 Gene

Gene Families for TNFAIP6 Gene

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

Protein Domains for TNFAIP6 Gene

InterPro:
Blocks:
  • CUB domain
  • Link domain

Suggested Antigen Peptide Sequences for TNFAIP6 Gene

GenScript: Design optimal peptide antigens:
  • Tumor necrosis factor alpha-induced protein 6 (TSG6_HUMAN)
genes like me logo Genes that share domains with TNFAIP6: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TNFAIP6 Gene

Function for TNFAIP6 Gene

Molecular function for TNFAIP6 Gene

UniProtKB/Swiss-Prot Function:
Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis.
UniProtKB/Swiss-Prot Induction:
By TNF.
GENATLAS Biochemistry:
tumor necrosis factor,alpha-induced protein 6

Phenotypes From GWAS Catalog for TNFAIP6 Gene

Gene Ontology (GO) - Molecular Function for TNFAIP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 18042364
GO:0005540 hyaluronic acid binding TAS,IEA --
genes like me logo Genes that share ontologies with TNFAIP6: view
genes like me logo Genes that share phenotypes with TNFAIP6: view

Animal Models for TNFAIP6 Gene

MGI Knock Outs for TNFAIP6:

Animal Models for research

  • Taconic Biosciences Mouse Models for TNFAIP6

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFAIP6

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TNFAIP6 Gene

Localization for TNFAIP6 Gene

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 TNFAIP6 gene
Compartment Confidence
extracellular 5
plasma membrane 3
nucleus 3
cytosol 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TNFAIP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA,IBA 21873635
GO:1904724 tertiary granule lumen TAS --
GO:1904813 ficolin-1-rich granule lumen TAS --
genes like me logo Genes that share ontologies with TNFAIP6: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Subcellular locations from the Human Protein Atlas (HPA) for TNFAIP6 Gene

Pathways & Interactions for TNFAIP6 Gene

PathCards logo

SuperPathways for TNFAIP6 Gene

SuperPathway Contained pathways
1 Akt Signaling
.60
.60
.55
2 Innate Immune System
3 PAK Pathway
.56
4 ERK Signaling
.51
5 PEDF Induced Signaling
.47
genes like me logo Genes that share pathways with TNFAIP6: view

Pathways by source for TNFAIP6 Gene

3 Reactome pathways for TNFAIP6 Gene
6 Qiagen pathways for TNFAIP6 Gene
  • Akt Signaling
  • Antioxidant Action of Vitamin-C
  • Molecular Mechanisms of Cancer
  • p38 Signaling
  • STAT3 Pathway

SIGNOR curated interactions for TNFAIP6 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for TNFAIP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006954 inflammatory response TAS 1730767
GO:0007155 cell adhesion IEA --
GO:0007165 signal transduction TAS 1730767
GO:0007267 cell-cell signaling TAS 1730767
GO:0030335 positive regulation of cell migration IEA --
genes like me logo Genes that share ontologies with TNFAIP6: view

Drugs & Compounds for TNFAIP6 Gene

(9) Drugs for TNFAIP6 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hyaluronic acid Approved, Vet_approved Pharma Target, binder 827
Aspirin Approved, Vet_approved Pharma Target, inhibitor, downregulator 1600
Donepezil Approved Pharma Target, inhibitor 327

(2) Additional Compounds for TNFAIP6 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TNFAIP6: view

Transcripts for TNFAIP6 Gene

mRNA/cDNA for TNFAIP6 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFAIP6

Alternative Splicing Database (ASD) splice patterns (SP) for TNFAIP6 Gene

No ASD Table

Relevant External Links for TNFAIP6 Gene

GeneLoc Exon Structure for
TNFAIP6

Expression for TNFAIP6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNFAIP6 Gene

mRNA differential expression in normal tissues according to GTEx for TNFAIP6 Gene

This gene is overexpressed in Whole Blood (x17.7).

Protein differential expression in normal tissues from HIPED for TNFAIP6 Gene

This gene is overexpressed in Islet of Langerhans (47.8) and Vitreous humor (21.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TNFAIP6 Gene



Protein tissue co-expression partners for TNFAIP6 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNFAIP6

SOURCE GeneReport for Unigene cluster for TNFAIP6 Gene:

Hs.437322

mRNA Expression by UniProt/SwissProt for TNFAIP6 Gene:

P98066-TSG6_HUMAN
Tissue specificity: Found in the synovial fluid of patients with rheumatoid arthritis.

Evidence on tissue expression from TISSUES for TNFAIP6 Gene

  • Spleen(4.4)
  • Lung(4.4)
  • Blood(2.9)
  • Kidney(2.6)
  • Intestine(2.4)
  • Heart(2.4)
  • Bone marrow(2.3)
  • Nervous system(2.1)
  • Muscle(2.1)
genes like me logo Genes that share expression patterns with TNFAIP6: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFAIP6 Gene

Orthologs for TNFAIP6 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNFAIP6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TNFAIP6 29 30
  • 99.64 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TSG-6 30
  • 94 (a)
OneToOne
TNFAIP6 29
  • 93.74 (n)
Dog
(Canis familiaris)
Mammalia TNFAIP6 29 30
  • 89.77 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Tnfaip6 29 16 30
  • 88.26 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TNFAIP6 30
  • 87 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TNFAIP6 30
  • 87 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tnfaip6 29
  • 86.62 (n)
Chicken
(Gallus gallus)
Aves TNFIP6 30
  • 79 (a)
OneToOne
TNFAIP6 29
  • 77.52 (n)
Lizard
(Anolis carolinensis)
Reptilia TNFAIP6 30
  • 64 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tnfaip6 29
  • 69.46 (n)
Zebrafish
(Danio rerio)
Actinopterygii tnfaip6 29 30
  • 70.06 (n)
OneToOne
Dr.17738 29
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
OneToMany
Species where no ortholog for TNFAIP6 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)
  • 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 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)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TNFAIP6 Gene

ENSEMBL:
Gene Tree for TNFAIP6 (if available)
TreeFam:
Gene Tree for TNFAIP6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFAIP6: view image
Alliance of Genome Resources:
Additional Orthologs for TNFAIP6

Paralogs for TNFAIP6 Gene

Paralogs for TNFAIP6 Gene

genes like me logo Genes that share paralogs with TNFAIP6: view

Variants for TNFAIP6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNFAIP6 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs1046668 -- p.Gln144Arg

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TNFAIP6 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TNFAIP6 Gene

Variant ID Type Subtype PubMed ID
dgv4094n100 CNV gain 25217958
esv34659 CNV loss 17911159
nsv1012891 CNV gain 25217958
nsv2972 CNV insertion 18451855
nsv834418 CNV gain 17160897

Variation tolerance for TNFAIP6 Gene

Residual Variation Intolerance Score: 75.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.01; 80.11% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFAIP6 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFAIP6
Leiden Open Variation Database (LOVD)
TNFAIP6

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFAIP6 Gene

Disorders for TNFAIP6 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TNFAIP6 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
arthritis
  • inflammatory disorder of joint
rheumatoid arthritis
  • ra
osteoarthritis
  • degenerative arthritis
chronic active epstein-barr virus infection
  • caebv infection
lipoprotein quantitative trait locus
  • lpaqtl
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TNFAIP6

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TNFAIP6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFAIP6 Gene

Publications for TNFAIP6 Gene

  1. A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression. (PMID: 11854277) Nentwich HA … Day AJ (The Journal of biological chemistry 2002) 3 4 22 40
  2. A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44. (PMID: 1730767) Lee TH … Vilcek J (The Journal of cell biology 1992) 2 3 4 22
  3. TSG-6 modulates the interaction between hyaluronan and cell surface CD44. (PMID: 15060082) Lesley J … Mikecz K (The Journal of biological chemistry 2004) 2 3 22
  4. TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo. (PMID: 8568267) Wisniewski HG … Cronstein BN (Journal of immunology (Baltimore, Md. : 1950) 1996) 2 3 22
  5. TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor. (PMID: 7516184) Wisniewski HG … Vilcek J (Biochemistry 1994) 3 4 22

Products for TNFAIP6 Gene

Sources for TNFAIP6 Gene