ADAMTS5
protein-codingADAM metallopeptidase with thrombospondin type 1 motif 5, the group of ADAM metallopeptidases with thrombospondin type 1 motif
Gene 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 disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and functions as an aggrecanase that cleaves aggrecan, a major proteoglycan of cartilage, and may mediate cartilage destruction in osteoarthritis. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADAMTS5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007038.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 143 | 3 | 146 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 143 | 1 | 5 | 149 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008969.2 | 8 | MANE Select | |
| Ensembl | ENSP00000284987.5 | 8 | MANE Select | |
| Ensembl | ENSP00000498989.1 | 4 | Standard | |
| Ensembl | ENSP00000640405.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin D Receptor Pathway
- Endochondral Ossification
- Post-translational protein modification
- Metabolism of proteins
- Extracellular matrix organization
Biological Process
- proteolysis
- extracellular matrix disassembly
- defense response to bacterium
- tooth eruption
- negative regulation of cold-induced thermogenesis
Molecular Function
- metalloendopeptidase activity
- integrin binding
- protein binding
- heparin binding
- metallopeptidase activity
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum lumen
- extracellular matrix
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000284987
- Coding exons
- 8
- Length
- 48602
- Individuals with no LoFs
- 125707
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125748
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.768 | 488 | 538 | 0.907 | 0.0000292 | 5947 |
| Missense (PolyPhen) | 173 | 234.62 | 0.73738 | 2589 | ||
| Synonymous | -1.56 | 258 | 228 | 1.13 | 0.0000130 | 1926 |
| Loss of Function | 2.93 | 16 | 34.6 | 0.463 | 0.00000164 | 418 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.00013 | 0.000092 | rare |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Metalloproteinase that plays an important role in connective tissue organization, development, inflammation, arthritis, and cell migration. ADAMTS5 is an extracellular matrix (ECM) degrading enzyme that show proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including aggrecan, versican, brevican and neurocan (PubMed:16133547, PubMed:18992360). Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle development through its versican remodeling properties. Participates in development of brown adipose tissue and browning of white adipose tissue. Plays an important role for T-lymphocyte migration from draining lymph nodes following viral infection. {ECO:0000250|UniProtKB:Q9R001, ECO:0000269|PubMed:16133547, ECO:0000269|PubMed:18992360}.;
Recessive Scores
- pRec
- 0.252
Intolerance Scores
- LoFtool
- 0.324
- RVIS EVS
- 0.25
- RVIS percentile EVS
- 69.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.292
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |