TNFAIP6 (TNF alpha induced protein 6)

Gene

• Entrez ID: 7130
• Gene name: TNF alpha induced protein 6
• Gene symbol: TNFAIP6
• Synonyms (NCBI Gene): TSG-6, TSG6
• Chromosome: 2
• Chromosome location: 2q23.3
• 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 c

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT573255	hsa-miR-2052	PAR-CLIP	20371350
MIRT573256	hsa-miR-19a-5p	PAR-CLIP	20371350
MIRT573254	hsa-miR-19b-1-5p	PAR-CLIP	20371350
MIRT573253	hsa-miR-19b-2-5p	PAR-CLIP	20371350
MIRT573255	hsa-miR-2052	PAR-CLIP	20371350
MIRT573256	hsa-miR-19a-5p	PAR-CLIP	20371350
MIRT573254	hsa-miR-19b-1-5p	PAR-CLIP	20371350
MIRT573253	hsa-miR-19b-2-5p	PAR-CLIP	20371350
MIRT2647470	hsa-miR-137	CLIP-seq
MIRT2647471	hsa-miR-23a	CLIP-seq
MIRT2647472	hsa-miR-23b	CLIP-seq
MIRT2647473	hsa-miR-23c	CLIP-seq
MIRT2647474	hsa-miR-3160-5p	CLIP-seq
MIRT2647475	hsa-miR-337-3p	CLIP-seq
MIRT2647476	hsa-miR-3647-3p	CLIP-seq
MIRT2647477	hsa-miR-3685	CLIP-seq
MIRT2647478	hsa-miR-384	CLIP-seq
MIRT2647479	hsa-miR-3924	CLIP-seq
MIRT2647480	hsa-miR-4446-5p	CLIP-seq
MIRT2647481	hsa-miR-4517	CLIP-seq
MIRT2647482	hsa-miR-4654	CLIP-seq
MIRT2647483	hsa-miR-4712-3p	CLIP-seq
MIRT2647484	hsa-miR-4755-5p	CLIP-seq
MIRT2647485	hsa-miR-4769-5p	CLIP-seq
MIRT2647486	hsa-miR-561	CLIP-seq
MIRT2647487	hsa-miR-579	CLIP-seq
MIRT2647470	hsa-miR-137	CLIP-seq
MIRT2647471	hsa-miR-23a	CLIP-seq
MIRT2647472	hsa-miR-23b	CLIP-seq
MIRT2647473	hsa-miR-23c	CLIP-seq
MIRT2647474	hsa-miR-3160-5p	CLIP-seq
MIRT2647475	hsa-miR-337-3p	CLIP-seq
MIRT2647476	hsa-miR-3647-3p	CLIP-seq
MIRT2647477	hsa-miR-3685	CLIP-seq
MIRT2647478	hsa-miR-384	CLIP-seq
MIRT2647479	hsa-miR-3924	CLIP-seq
MIRT2647480	hsa-miR-4446-5p	CLIP-seq
MIRT2647481	hsa-miR-4517	CLIP-seq
MIRT2647482	hsa-miR-4654	CLIP-seq
MIRT2647483	hsa-miR-4712-3p	CLIP-seq
MIRT2647484	hsa-miR-4755-5p	CLIP-seq
MIRT2647485	hsa-miR-4769-5p	CLIP-seq
MIRT2647486	hsa-miR-561	CLIP-seq
MIRT2647487	hsa-miR-579	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CEBPB	Activation	7876106
CEBPB	Unknown	7935377
CEBPD	Activation	23028973

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001550	Process	Ovarian cumulus expansion	IEA
GO:0001550	Process	Ovarian cumulus expansion	ISS
GO:0001968	Function	Fibronectin binding	IDA	18042364
GO:0005509	Function	Calcium ion binding	IDA	26468290
GO:0005515	Function	Protein binding	IPI	16771708, 18042364, 18586671, 22267482, 24501198, 26468290, 27044744
GO:0005540	Function	Hyaluronic acid binding	IDA	26468290, 26823460
GO:0005540	Function	Hyaluronic acid binding	IEA
GO:0005540	Function	Hyaluronic acid binding	TAS	1730767
GO:0005576	Component	Extracellular region	IDA	1730767
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0006954	Process	Inflammatory response	TAS	1730767
GO:0007155	Process	Cell adhesion	IEA
GO:0007165	Process	Signal transduction	TAS	1730767
GO:0007267	Process	Cell-cell signaling	TAS	1730767
GO:0016787	Function	Hydrolase activity	IEA
GO:0030212	Process	Hyaluronan metabolic process	IDA	20463016, 26468290
GO:0030335	Process	Positive regulation of cell migration	IEA
GO:0030514	Process	Negative regulation of BMP signaling pathway	IDA	16771708
GO:0045668	Process	Negative regulation of osteoblast differentiation	IDA	16771708, 18586671
GO:0045671	Process	Negative regulation of osteoclast differentiation	IDA	18586671
GO:0046872	Function	Metal ion binding	IEA
GO:0050728	Process	Negative regulation of inflammatory response	IBA
GO:0050728	Process	Negative regulation of inflammatory response	IDA	21569482
GO:0090024	Process	Negative regulation of neutrophil chemotaxis	IDA	24501198
GO:0106435	Function	Carboxylesterase activity	IDA	16873769, 20463016
GO:1903911	Process	Positive regulation of receptor clustering	IDA	26823460
GO:1904724	Component	Tertiary granule lumen	TAS
GO:1904813	Component	Ficolin-1-rich granule lumen	TAS
GO:1905590	Process	Fibronectin fibril organization	IDA	18042364

Other IDs

• MIM: 600410
• HGNC: 11898
• e!Ensembl: ENSG00000123610

Protein

• UniProt ID: P98066
• Protein name: Tumor necrosis factor-inducible gene 6 protein (EC 3.1.1.-) (Hyaluronate-binding protein) (TNF-stimulated gene 6 protein) (TSG-6) (Tumor necrosis factor alpha-induced protein 6) (TNF alpha-induced protein 6)
• Protein function: Major regulator of extracellular matrix organization during tissue remodeling (PubMed:15917224, PubMed:18042364, PubMed:26823460). Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves
• PDB: 1O7B, 1O7C, 2N40, 2PF5, 2WNO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00193	Xlink	36 → 128	Extracellular link domain	Domain
  PF00431	CUB	135 → 244	CUB domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in airway epithelium and submucosal gland (at protein level). Colocalizes with bikunin at the ciliary border. Present in bronchoalveolar lavage fluid (at protein level) (PubMed:16873769). Expressed in mesenchymal stem cells (
• Sequence:

  MIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAVCEF
  EGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRS
  ERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQRIHLSFLDF
  DLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLKFLSDASVTAGGF
  QIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHL

• Sequence length: 277

Pathways

Reactome:

Neutrophil degranulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ARTHRITIS, JUVENILE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORNEAL NEOVASCULARIZATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATITIS, ALLERGIC CONTACT	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATOLOGIC DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC MACULOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE CHRONIC POLYARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MONOARTICULAR JUVENILE RHEUMATOID ARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PAUCIARTICULAR JUVENILE RHEUMATOID ARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES, GENETIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute pancreatitis	Pancreatitis	BEFREE	30257717		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	30507579	Stimulate	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm Abdominal	Aortic aneurysm	Pubtator	29180197	Stimulate	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm, Abdominal	Aortic Aneurysm	BEFREE	29180197		★☆☆☆☆ Found in Text Mining only
Aortic valve disorder	Aortic Valve Disease	BEFREE	27856308		★☆☆☆☆ Found in Text Mining only
Arsenic Encephalopathy	Arsenic Encephalopathy	CTD_human_DG	16835338		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	29401724		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	12209527, 29868252		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	26685054, 37958918, 9237673	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Psoriatic	Psoriatic arthritis	Pubtator	11178946	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	11178946, 12823853, 15549486, 21162099, 33897688, 34177888, 35353944	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	37958839	Stimulate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	16873769	Associate	★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	29401724		★☆☆☆☆ Found in Text Mining only
Bloom Syndrome	Bloom syndrome	Pubtator	32073752	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31044513		★☆☆☆☆ Found in Text Mining only
Bronchopulmonary Dysplasia	Bronchopulmonary Dysplasia	BEFREE	29941022, 30538263		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	1730767	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	30595463		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	26831905, 28004769	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	29401724		★☆☆☆☆ Found in Text Mining only
Cerebral Amyloid Angiopathy	Cerebral amyloid angiopathy	Pubtator	32993718	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	29401724		★☆☆☆☆ Found in Text Mining only
Cholangitis Sclerosing	Sclerosing cholangitis	Pubtator	17162367	Stimulate	★☆☆☆☆ Found in Text Mining only
Chronic interstitial cystitis	Interstitial Cystitis	BEFREE	29299202		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	28701721, 29625582		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	19383344, 20846378, 25516661, 34294834	Associate	★☆☆☆☆ Found in Text Mining only
Contracture	Contracture	Pubtator	21239672	Inhibit	★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	27739342		★☆☆☆☆ Found in Text Mining only
Corneal Injuries	Corneal injury	Pubtator	24501198	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	29401724		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn disease	Pubtator	26339133	Associate	★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	27088253		★☆☆☆☆ Found in Text Mining only
Cutaneous Mastocytosis	Cutaneous mastocytosis	BEFREE	25890163		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	11854277, 16139532, 29129649, 29564448, 29868252		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	LHGDN	11854277		★☆☆☆☆ Found in Text Mining only
Dermatitis, Allergic Contact	Dermatitis	CTD_human_DG	16033404, 17374397		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dermatologic disorders	Dermatologic Disorders	CTD_human_DG	16835338		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	37948519	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	24677718, 29483622		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASCAT_DG	31264924		★☆☆☆☆ Found in Text Mining only
Diabetic Foot	Diabetic foot	Pubtator	35013299	Associate	★☆☆☆☆ Found in Text Mining only
Dry Eye Syndromes	Dry eye syndrome	Pubtator	32829938	Inhibit	★☆☆☆☆ Found in Text Mining only
Eosinophilic Esophagitis	Eosinophilia	Pubtator	23503644, 37652141	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty liver	Pubtator	37657050	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	35766985	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	38225203	Associate	★☆☆☆☆ Found in Text Mining only
Glomerulonephritis IGA	Iga nephropathy	Pubtator	32938960	Associate	★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	34344926	Associate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	35457151	Stimulate	★☆☆☆☆ Found in Text Mining only
Infarction, Middle Cerebral Artery	Cerebral Infraction	CTD_human_DG	12374626		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	27088253, 28701721, 29625582, 31558705		★☆☆☆☆ Found in Text Mining only
Interstitial Cystitis	Interstitial Cystitis	BEFREE	29299202		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	29483622		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	33536009	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	36578051	Stimulate	★☆☆☆☆ Found in Text Mining only
Intervertebral disc disease	Intervertebral disc disease	Pubtator	15549486	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral disc disorder	Intervertebral Disc Disorder	BEFREE	29483622		★☆☆☆☆ Found in Text Mining only
Ischemic Stroke	Ischemic stroke	Pubtator	35222359	Associate	★☆☆☆☆ Found in Text Mining only
Juvenile arthritis	Arthritis	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Juvenile psoriatic arthritis	Juvenile arthritis	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Juvenile-Onset Still Disease	Still Disease	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	32938960	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure, Acute	Kidney Failure	BEFREE	30984789		★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	32317078	Associate	★☆☆☆☆ Found in Text Mining only
Liver Failure, Acute	Liver failure	BEFREE	25890163		★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	BEFREE	24242012		★☆☆☆☆ Found in Text Mining only
Maculopathy with diabetes mellitus	Diabetic maculopathy	GWASCAT_DG	31264924		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31044513		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	31044513		★☆☆☆☆ Found in Text Mining only
Middle Cerebral Artery Thrombosis	Cerebral Thrombosis	CTD_human_DG	12374626		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	30569148	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	32951330	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	20643923		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial infarction	Pubtator	24501198, 31772617	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	33564686	Stimulate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16467113, 31044513		★☆☆☆☆ Found in Text Mining only
Nevus comedonicus	Nevus comedonicus	BEFREE	25890163		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	11178946, 11854277, 24894724, 25054223, 25575966, 29129649	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	16139532	Inhibit	★☆☆☆☆ Found in Text Mining only
Osteoarthritis Knee	Osteoarthritis	Pubtator	16453284	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis of hip	Osteoarthritis Of Hip	BEFREE	15210948		★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	BEFREE	25575966		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	39972314	Stimulate	★☆☆☆☆ Found in Text Mining only
Polyarthritis, Juvenile, Rheumatoid Factor Negative	Seronegative polyarthritis	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Polyarthritis, Juvenile, Rheumatoid Factor Positive	Polyarthritis, Rheumatoid Factor Positive	CTD_human_DG	19565504		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	25393639, 28004769	Associate	★☆☆☆☆ Found in Text Mining only
Prion Diseases	Prion disease	Pubtator	36581683	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	16467113		★☆☆☆☆ Found in Text Mining only
Sepsis	Sepsis	Pubtator	31093495	Associate	★☆☆☆☆ Found in Text Mining only
Spondylitis Ankylosing	Ankylosing spondylitis	Pubtator	39185422	Inhibit	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	35854776, 37201873	Associate	★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	27088253, 31547322		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	40247223	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	40776873	Stimulate	★☆☆☆☆ Found in Text Mining only
Urothelial Carcinoma	Urothelial Carcinoma	BEFREE	30595463		★☆☆☆☆ Found in Text Mining only