TNFAIP6 TNF alpha induced protein 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNFAIP6provided by HGNC
Official Full Name: TNF alpha induced protein 6provided by HGNC
Primary source: HGNC:HGNC:11898
See related: Ensembl:ENSG00000123610 MIM:600410; AllianceGenome:HGNC:11898
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TSG6; TSG-6
Summary: 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]
Expression: Biased expression in appendix (RPKM 17.8), gall bladder (RPKM 12.0) and 11 other tissues See more
Orthologs: all
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Genomic context

Location:: 2q23.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (151357592..151381340)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (151809346..151833086)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (152214106..152236560)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Endogenous TSG-6 modulates corneal inflammation following chemical injury.
Title: Endogenous TSG-6 modulates corneal inflammation following chemical injury.
DKC1 aggravates gastric cancer cell migration and invasion through up-regulating the expression of TNFAIP6.
Title: DKC1 aggravates gastric cancer cell migration and invasion through up-regulating the expression of TNFAIP6.
Human Synovial Mesenchymal Stem Cells Expressed Immunoregulatory Factors IDO and TSG6 in a Context of Arthritis Mediated by Alphaviruses.
Title: Human Synovial Mesenchymal Stem Cells Expressed Immunoregulatory Factors IDO and TSG6 in a Context of Arthritis Mediated by Alphaviruses.
TWIST1 and TSG6 are coordinately regulated and function as potency biomarkers in human MSCs.
Title: TWIST1 and TSG6 are coordinately regulated and function as potency biomarkers in human MSCs.
Hsa_circ_0002019 promotes cell proliferation, migration, and invasion by regulating TNFAIP6/NF-kappaB signaling in gastric cancer.
Title: Hsa_circ_0002019 promotes cell proliferation, migration, and invasion by regulating TNFAIP6/NF-κB signaling in gastric cancer.
Tumour necrosis factor stimulated gene 6 intrinsically regulates PD-L1 expressions in breast cancer cells, leading to modulation of tumour microenvironment.
Title: Tumour necrosis factor stimulated gene 6 intrinsically regulates PD-L1 expressions in breast cancer cells, leading to modulation of tumour microenvironment.
TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1alpha/TRAF2/NF-kappaB signalling.
Title: TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF-κB signalling.
TSG-6 inhibits IL-1beta-induced inflammatory responses and extracellular matrix degradation in nucleus pulposus cells by activating the PI3K/Akt signaling pathway.
Title: TSG-6 inhibits IL-1β-induced inflammatory responses and extracellular matrix degradation in nucleus pulposus cells by activating the PI3K/Akt signaling pathway.
An update on the role of tumor necrosis factor alpha stimulating gene-6 in inflammatory diseases.
Title: An update on the role of tumor necrosis factor alpha stimulating gene-6 in inflammatory diseases.
[Expression of TNFAIP6 in oral verrucous carcinoma and oral squamous cell carcinoma and its relationship with clinicopathology].
Title: [Expression of TNFAIP6 in oral verrucous carcinoma and oral squamous cell carcinoma and its relationship with clinicopathology].

Submit: New GeneRIF Correction See all GeneRIFs (89)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) in human B cells	PubMed
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) in primary human brain microvascular endothelial cells	PubMed
	tat	HIV-1 and the viral protein Tat modulate the expression of tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) in immature dendritic cells and monocyte-derived macrophages	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TNFAIP6_1246 (e-PCR)
- UniSTS:277826

SHGC-85360 (e-PCR)
- UniSTS:104887

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables carboxylesterase activity	IDA Inferred from Direct Assay more info	PubMed
enables fibronectin binding	IDA Inferred from Direct Assay more info	PubMed
enables hyaluronic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables hyaluronic acid binding	IEA Inferred from Electronic Annotation more info
enables hyaluronic acid binding	TAS Traceable Author Statement more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in fibronectin fibril organization	IDA Inferred from Direct Assay more info	PubMed
involved_in hyaluronan metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of osteoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of osteoclast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in ovarian cumulus expansion	IEA Inferred from Electronic Annotation more info
involved_in ovarian cumulus expansion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of receptor clustering	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tumor necrosis factor-inducible gene 6 protein

Names: TNF-stimulated gene 6 protein; hyaluronate-binding protein; tumor necrosis factor alpha-inducible protein 6; tumor necrosis factor, alpha induced protein 6; tumor necrosis factor-stimulated gene-6 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_007115.4 → NP_009046.2 tumor necrosis factor-inducible gene 6 protein precursor

See identical proteins and their annotated locations for NP_009046.2

Status: REVIEWED

Source sequence(s)

AC009311, AU102580, BC030205

Consensus CDS

CCDS2193.1

UniProtKB/Swiss-Prot

P98066, Q53TI7, Q8WWI9

Related

ENSP00000243347.3, ENST00000243347.5

Conserved Domains (2) summary

cd03515
Location:36 → 128

Link_domain_TSG_6_like; This is the extracellular link domain of the type found in human TSG-6. The link domain is a hyaluronan (HA)-binding domain. TSG-6 is the protein product of tumor necrosis factor-stimulated gene-6. TSG-6 is up-regulated in inflammatory lesions and in the ...

pfam00431
Location:135 → 244

CUB; CUB domain