ADAMTS3
protein-codingADAM metallopeptidase with thrombospondin type 1 motif 3, 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 protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [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 ~288.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032564
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016256
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0032564
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032564
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Gastrointestinal
Intervention: Endocrine; Gastrointestinal
Rationale: The condition can include manifestations such as protein-losing enteropathy, and awareness may allow prompt diagnosis and management (such as nutrition via feeding tube), Endocrine manifestations such as growth hormone deficiency have been observed, and awareness may allow prompt recognition and treatment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADAMTS3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014243.3. 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 | 2 | 35 | 2 | 39 | ||
| missense | 2 | 172 | 14 | 5 | 193 | |
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 3 | 0 | 176 | 49 | 7 | 235 |
Highest pathogenic variant AF is 0.0000068460045
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055058.2 | 22 | MANE Select | |
| Ensembl | ENSP00000286657.4 | 22 | MANE Select | |
| Ensembl | ENSP00000779488.1 | 3 | Standard | |
| Ensembl | ENSP00000804630.1 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Collagen biosynthesis and modifying enzymes
- Post-translational protein modification
- Metabolism of proteins
- Collagen formation
- Extracellular matrix organization
Biological Process
- vascular endothelial growth factor production
- protein processing
- collagen fibril organization
- collagen catabolic process
- collagen biosynthetic process
Molecular Function
- endopeptidase activity
- metalloendopeptidase activity
- protein binding
- heparin binding
- zinc ion binding
Cellular Component
- extracellular region
- extracellular space
- extracellular matrix
- collagen-containing extracellular matrix
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000286657
- Coding exons
- 22
- Length
- 287831
- Individuals with no LoFs
- 125677
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 71
- Defined
- 125748
- p
- 0.000282
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.545 | 641 | 681 | 0.941 | 0.0000369 | 7960 |
| Missense (PolyPhen) | 161 | 200.5 | 0.80299 | 2274 | ||
| Synonymous | 0.384 | 228 | 236 | 0.968 | 0.0000128 | 2231 |
| Loss of Function | 4.13 | 28 | 63.5 | 0.441 | 0.00000343 | 742 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00045 | 0.00043 | rare |
| Ashkenazi Jewish | 0.00020 | 0.000099 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00029 | 0.00029 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00035 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cleaves the propeptides of type II collagen prior to fibril assembly. Does not act on types I and III collagens.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- LoFtool
- 0.450
- RVIS EVS
- -0.65
- RVIS percentile EVS
- 16.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.144
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |