ADAMTS9
ADAMTS9 (A disintegrin and metalloproteinase with thrombospondin motifs 9) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
Overview
Cleaves the large aggregating proteoglycans, aggrecan (at the '1838-Glu-|-Ala-1839' site) and versican (at the '1428-Glu-|-Ala-1429' site). In addition, catalyses the shedding of the endopeptidase MMP14 (at the '314-Tyr-|-Gly-315' site), releasing the catalytic domain from the cell surface thereby preventing the downstream pro-MMP2 activation. Is involved in extracellular matrix proteolysis and in ciliary vesicle growth during ciliogenesis in metalloendopeptidase activity dependent manner.
Open Targets scores its association with cancer at 0.54 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.63, somatic mutation 0.33). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Plasma Cell Myeloma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · ADAMTS9 (A disintegrin and metalloproteinase with thrombospondin motifs 9) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
- 1 · What it is
ADAMTS9 (A disintegrin and metalloproteinase with thrombospondin motifs 9) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
- 2 · What goes wrong in cancer
Cleaves the large aggregating proteoglycans, aggrecan (at the '1838-Glu-|-Ala-1839' site) and versican (at the '1428-Glu-|-Ala-1429' site).
- 3 · How drugs use it
No product in this corpus aims at ADAMTS9 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:13202 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9P2N4 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000163638 (association with cancer (MONDO_0004992) 0.54; (GraphQL API, CC0)); IntOGen ADAMTS9 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Cleaves the large aggregating proteoglycans, aggrecan (at the '1838-Glu-|-Ala-1839' site) and versican (at the '1428-Glu-|-Ala-1429' site). In addition, catalyses the shedding of the endopeptidase MMP14 (at the '314-Tyr-|-Gly-315' site), releasing the catalytic domain from the cell surface thereby preventing the downstream pro-MMP2 activation. Is involved in extracellular matrix proteolysis and in ciliary vesicle growth during ciliogenesis in metalloendopeptidase activity dependent manner. Has a protease-independent function in promoting the transport from the endoplasmic reticulum to the Golgi apparatus of a variety of secretory cargos. Location: Secreted, extracellular space, extracellular matrix; Endoplasmic reticulum; Cell projection, cilium; Recycling endosome (UniProt). Locus 3p14.1 (HGNC).
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"ADAMTS9" OR ABSTRACT:"ADAMTS9" OR TITLE:"ADAM metallopeptidase with thrombospondin type 1 motif 9" OR ABSTRACT:"ADAM metallopeptidase with thrombospondin type 1 motif 9" OR TITLE:"A disintegrin and metalloproteinase with thrombospondin motifs 9" OR ABSTRACT:"A disintegrin and metalloproteinase with thrombospondin motifs 9" OR TITLE:"KIAA1312" OR ABSTRACT:"KIAA1312") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ADAMTS9, not a curated reading list.