ADAMTS12 (ADAM metallopeptidase with thrombospondin type 1 motif 12)

Gene

• Entrez ID: 81792
• Gene name: ADAM metallopeptidase with thrombospondin type 1 motif 12
• Gene symbol: ADAMTS12
• Synonyms (NCBI Gene): PRO4389
• Chromosome: 5
• Chromosome location: 5p13.3-p13.2
• Summary: This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegri

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018249	hsa-miR-335-5p	Microarray	18185580
MIRT029674	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001503	Process	Ossification	IEA
GO:0002062	Process	Chondrocyte differentiation	IEA
GO:0004222	Function	Metalloendopeptidase activity	IBA
GO:0004222	Function	Metalloendopeptidase activity	IDA	16611630, 17895370, 18485748
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	16611630, 18485748, 25416956, 31515488, 32296183
GO:0005576	Component	Extracellular region	IEA
GO:0006029	Process	Proteoglycan metabolic process	IEA
GO:0006508	Process	Proteolysis	IBA
GO:0006508	Process	Proteolysis	IEA
GO:0007160	Process	Cell-matrix adhesion	IMP	21494557
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0016477	Process	Cell migration	IMP	21494557
GO:0016787	Function	Hydrolase activity	IEA
GO:0030167	Process	Proteoglycan catabolic process	IDA	17895370
GO:0030198	Process	Extracellular matrix organization	IBA
GO:0030198	Process	Extracellular matrix organization	IEA
GO:0030199	Process	Collagen fibril organization	IEA
GO:0031012	Component	Extracellular matrix	IBA
GO:0032331	Process	Negative regulation of chondrocyte differentiation	IDA	22247065
GO:0032331	Process	Negative regulation of chondrocyte differentiation	IEA
GO:0043931	Process	Ossification involved in bone maturation	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050727	Process	Regulation of inflammatory response	IDA	23019333
GO:0051603	Process	Proteolysis involved in protein catabolic process	IDA	16611630
GO:0051603	Process	Proteolysis involved in protein catabolic process	IMP	18485748
GO:0071347	Process	Cellular response to interleukin-1	IEA
GO:0071347	Process	Cellular response to interleukin-1	IMP	18485748
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IMP	18485748
GO:0071773	Process	Cellular response to BMP stimulus	IDA	22247065
GO:0071773	Process	Cellular response to BMP stimulus	IEA
GO:1901509	Process	Regulation of endothelial tube morphogenesis	IDA	17895370
GO:1902203	Process	Negative regulation of hepatocyte growth factor receptor signaling pathway	IDA	17895370
GO:1902548	Process	Negative regulation of cellular response to vascular endothelial growth factor stimulus	IDA	17895370
GO:2001113	Process	Negative regulation of cellular response to hepatocyte growth factor stimulus	IDA	17895370

Other IDs

• MIM: 606184
• HGNC: 14605
• e!Ensembl: ENSG00000151388

Protein

• UniProt ID: P58397
• Protein name: A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAM-TS 12) (ADAM-TS12) (ADAMTS-12) (EC 3.4.24.-)
• Protein function: Metalloprotease that may play a role in the degradation of COMP. Also cleaves alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01562	Pep_M12B_propep	53 → 195	Reprolysin family propeptide	Family
  PF01421	Reprolysin	246 → 456	Reprolysin (M12B) family zinc metalloprotease	Domain
  PF17771	ADAM_CR_2	468 → 532	ADAM cysteine-rich domain	Domain
  PF00090	TSP_1	546 → 596	Thrombospondin type 1 domain	Domain
  PF05986	ADAM_spacer1	702 → 813	ADAM-TS Spacer 1	Family
  PF19030	TSP1_ADAMTS	828 → 882		Domain
  PF19030	TSP1_ADAMTS	886 → 943		Domain
  PF19030	TSP1_ADAMTS	948 → 996		Domain
  PF19030	TSP1_ADAMTS	1317 → 1365		Domain
  PF19030	TSP1_ADAMTS	1368 → 1424		Domain
  PF19030	TSP1_ADAMTS	1427 → 1472		Domain
  PF19030	TSP1_ADAMTS	1475 → 1531		Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in skeletal muscle and fat. {ECO:0000269|PubMed:16611630}.
• Sequence:

  MPCAQRSWLANLSVVAQLLNFGALCYGRQPQPGPVRFPDRRQEHFIKGLPEYHVVGPVRV
  DASGHFLSYGLHYPITSSRRKRDLDGSEDWVYYRISHEEKDLFFNLTVNQGFLSNSYIME
  KRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLPHGDFFIEPVK
  KHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLSRR
  SISKERWVETLVVADTKMIEYHGSENVESYILTIMNMVTGLFHNPSIGNAIHIVVVRLIL
  LEEEEQGLKIVHHAEKTLSSFCKWQKSINPKSDLNPVHHDVAVLLTRKDICAGFNRPCET
  LGLSHLSGMCQPHRSCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMS
  RQLQYDPTPLTWSKCSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQL
  QYGPNATFCQEVENVCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPES
  IPGGWGRWSPWSHCSRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEA
  PTFRQMQCSEFDTVPYKNELYHWFPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFE
  GGNSRNVCINGICKMVGCDYEIDSNATEDRCGVCLGDGSSCQTVRKMFKQKEGSGYVDIG
  LIPKGARDIRVMEIEGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTVFQYDRKGDL
  EKLMATGPTNESVWIQLLFQVTNPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTC
  GTGIRRQTAHCIKKGRGMVKATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGP
  HGEKKRTVLCIQTMVSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSC
  GGGVRIRSVTCAKNHDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLK
  PVPPPTSRPRMLTTPTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRY
  LISTGSTSQPILTSQSLSIQPSEENVSSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPV
  TPFYNTLTKGPEMEIHSGSGEEREQPEDKDESNPVIWTKIRVPGNDAPVESTEMPLAPPL
  TPDLSRESWWPPFSTVMEGLLPSQRPTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPS
  GKTANRNHLKLPNNMNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSAHWIVG
  NWSECSTTCGLGAYWRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNC
  SGGFKIREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCG
  GGVQERGVFCPGGLCDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVP
  SEGNKTEDQDQCLCDHKPRPPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSV
  PTVRAECCFSCPQTHITHTQRQRRQRLLQKSKEL

• Sequence length: 1594

Pathways

Reactome:

Defective B3GALTL causes Peters-plus syndrome (PpS)
O-glycosylation of TSR domain-containing proteins

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
BASAL CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BEHCET'S SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CUTANEOUS MELANOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis	Arthritis	LHGDN	16611630, 19098927		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	20506400, 22505177, 29750395		★☆☆☆☆ Found in Text Mining only
Arthritis Psoriatic	Psoriatic arthritis	Pubtator	18485748	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	20506400	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	16890764, 22962682		★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	BEFREE	25756154		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24457941		★☆☆☆☆ Found in Text Mining only
Bronchial Hyperreactivity	Bronchial Hyperreactivity	BEFREE	16890764		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	37819632	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	19638407		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	32376891	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	39940703	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Aneurysm	Cerebral Aneurysm	BEFREE	26745484		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	19638407		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31632555, 31632580		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	14730609, 30903650		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	19638407		★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	37819632	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24457941		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	19638407		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	19638407		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24457941		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	30977985		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	14730609	Stimulate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	18485748, 20506400, 27449198, 30903650	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	34198725	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	22005949, 22505177, 29750395		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	22322903		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	22322903		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	31236983		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	11279086, 34040054	Associate	★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	32817637	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	37092087	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Diseases	Uterine polyp	Pubtator	38340595	Stimulate	★☆☆☆☆ Found in Text Mining only
Venous Thromboembolism	Venous thromboembolism	Pubtator	32817637	Associate	★☆☆☆☆ Found in Text Mining only