ADAMTS6
protein-codingADAM metallopeptidase with thrombospondin type 1 motif 6, 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. Expression of this gene may be regulated by the cytokine TNF-alpha. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~333.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADAMTS6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_197941.4. 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 | 1 | 1 | ||||
| missense | 1 | 107 | 6 | 1 | 115 | |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 110 | 6 | 1 | 118 |
Highest pathogenic variant AF is 0.0000018587338
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_922932.2 | 24 | MANE Select | |
| Ensembl | ENSP00000370443.3 | 24 | MANE Select | |
| Ensembl | ENSP00000424377.1 | 5 | Standard | |
| Ensembl | ENSP00000811194.1 | 24 | 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
- cardiac septum development
- proteolysis
- aorta development
- coronary vasculature development
Molecular Function
- metalloendopeptidase activity
- metallopeptidase activity
- metal ion binding
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381055
- Coding exons
- 24
- Length
- 333185
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125748
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.09 | 402 | 618 | 0.650 | 0.0000322 | 7386 |
| Missense (PolyPhen) | 86 | 219.76 | 0.39134 | 2546 | ||
| Synonymous | 0.0637 | 205 | 206 | 0.994 | 0.0000102 | 2028 |
| Loss of Function | 6.59 | 8 | 65.5 | 0.122 | 0.00000343 | 764 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.309
- RVIS EVS
- -0.57
- RVIS percentile EVS
- 18.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.382
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |