ADAMTS12
protein-codingADAM metallopeptidase with thrombospondin type 1 motif 12, 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-1) motif. Individual members of this family differ in the number of C-terminal TS-1 motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains eight TS-1 motifs. It may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~368.5 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 ADAMTS12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030955.4. 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 | 15 | 3 | 3 | 21 | ||
| missense | 252 | 13 | 5 | 270 | ||
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 279 | 16 | 8 | 303 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_112217.2 | 24 | MANE Select | |
| Ensembl | ENSP00000422554.1 | 24 | MANE Select | |
| RefSeq | NP_001311440.1 | 3 | Standard | |
| RefSeq | NP_001311441.1 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- O-glycosylation of TSR domain-containing proteins
- O-linked glycosylation
Biological Process
- cell-matrix adhesion
- cell migration
- proteoglycan catabolic process
- negative regulation of chondrocyte differentiation
- regulation of inflammatory response
Molecular Function
- metalloendopeptidase activity
- protein binding
- metal ion binding
Cellular Component
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000504830
- Coding exons
- 24
- Length
- 368658
- Individuals with no LoFs
- 125542
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 206
- Defined
- 125748
- p
- 0.000819
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.980 | 819 | 902 | 0.908 | 0.0000493 | 10502 |
| Missense (PolyPhen) | 270 | 351.73 | 0.76762 | 4027 | ||
| Synonymous | -0.0799 | 340 | 338 | 1.01 | 0.0000199 | 3044 |
| Loss of Function | 3.80 | 40 | 75.7 | 0.528 | 0.00000369 | 877 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0.0037 | 0.0037 | notable |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00068 | 0.00067 | rare |
| South Asian | 0.00089 | 0.00085 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Metalloprotease that may play a role in the degradation of COMP. Cleaves also alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties. {ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:17895370, ECO:0000269|PubMed:18485748}.;
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- LoFtool
- 0.867
- RVIS EVS
- 0.87
- RVIS percentile EVS
- 88.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.160
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |