ADAMTS4
ADAM Metallopeptidase with Thrombospondin Type 1 Motif 4
Gene Information Card
| Symbol | ADAMTS4 |
|---|---|
| Full Name | ADAM Metallopeptidase with Thrombospondin Type 1 Motif 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 9507 ncbi.nlm.nih.gov/gene/9507 |
| Ensembl ID | ENSG00000158859 |
| UniProt ID | O75173 |
| OMIM ID | 603876 |
| HGNC ID | 220 |
| Aliases | ADAMTS-4, ADMP-1, aggrecanase-1 |
Description
ADAMTS4 encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of zinc-dependent proteases. The encoded preproprotein is proteolytically processed to generate the mature enzyme, which functions as aggrecanase-1, cleaving aggrecan, a major proteoglycan of cartilage. This enzyme plays a key role in extracellular matrix degradation and remodeling, particularly in articular cartilage, and is implicated in osteoarthritis and other inflammatory joint diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoarthritis | ADAMTS4 cleaves aggrecan in cartilage, leading to matrix degradation and joint destruction. | OMIM 603876; multiple association studies |
| Rheumatoid Arthritis | Elevated ADAMTS4 expression in synovial fluid contributes to cartilage erosion. | PubMed studies; ClinVar |
| Intervertebral Disc Degeneration | ADAMTS4-mediated aggrecan cleavage in disc tissue promotes degeneration. | NCBI Gene; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 5.1 | Low |
| Kidney | 8.7 | Medium |
| Liver | 2.0 | Not detected |
| Lung | 6.4 | Low |
| Muscle | 1.5 | Not detected |
| Ovary | 15.2 | Medium |
| Placenta | 20.8 | High |
| Skin | 18.5 | High |
| Testis | 25.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 22.0 | High expression |
| HeLa | 8.3 | Moderate expression |
| HepG2 | 3.1 | Low expression |
| K562 | 1.2 | Not detected |
| MCF7 | 12.7 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1019C>T (p.Thr340Met) | Missense | Rare | Unknown functional effect |
| c.1522G>A (p.Gly508Arg) | Missense | Rare | Unknown functional effect |
| c.1960_1962del (p.Lys654del) | In-frame deletion | Rare | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ClinVar or COSMIC for ADAMTS4.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity | • extracellular matrix disassembly |
| • proteoglycan catabolic process | • zinc ion binding |
| • aggrecanase activity |
Pathways
• ECM degradation (Reactome R-HSA-1474228)
• Aggrecan catabolism (Reactome R-HSA-2022090)
Protein Summary
ADAMTS4 (aggrecanase-1) is a secreted zinc-dependent metalloproteinase that cleaves aggrecan at specific sites, leading to cartilage degradation. The protein contains a signal peptide, a prodomain, a catalytic domain with a zinc-binding motif, a disintegrin-like domain, and thrombospondin type 1 repeats. It is synthesized as a zymogen and activated by furin-like proprotein convertases. ADAMTS4 is a key enzyme in the pathophysiology of osteoarthritis and other arthritic conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAMTS4 Knockout HEK293 Cell Line | EDJ-KQ50874 | Human | 9507 | Details Get a Quote |
| ADAMTS4 Knockout HeLa Cell Line | EDJ-KQ55184 | Human | 9507 | Details Get a Quote |
| ADAMTS4 Knockout A-549 Cell Line | EDJ-KQ63663 | Human | 9507 | Details Get a Quote |
| ADAMTS4 Knockout HCT 116 Cell Line | EDJ-KQ72124 | Human | 9507 | Details Get a Quote |
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