ADAMTS17
protein-codingADAM metallopeptidase with thrombospondin type 1 motif 17, 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. ADAMTS family members 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 protein, which may promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. [provided by RefSeq, May 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~370.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013176
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013176
Submitter: Illumina
Inheritance Pattern: AR
Disease ID:MONDO:0013176
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013176
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013176
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013176
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Ophthalmologic
Intervention: Ophthalmologic; Pharmacogenomic
Rationale: Individuals may be at risk of glaucoma, and surveillance may allow early management and preventive measures; Agents that may contribute to glaucoma should be avoided
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADAMTS17 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139057.4. 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 | 10 | 367 | 6 | 383 | ||
| missense | 1 | 5 | 469 | 24 | 1 | 500 |
| nonsense | 19 | 7 | 4 | 30 | ||
| start loss | 0 | |||||
| frameshift | 21 | 6 | 3 | 30 | ||
| splice donor/acceptor (+/-2bp) | 1 | 17 | 4 | 22 | ||
| Total | 42 | 35 | 490 | 391 | 7 | 965 |
Highest pathogenic variant AF is 0.000048336362
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_620688.2 | 22 | MANE Select | |
| Ensembl | ENSP00000268070.4 | 22 | MANE Select | |
| Ensembl | ENSP00000453604.1 | 2 | Standard | |
| Ensembl | ENSP00000458005.1 | 3 | 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
- proteolysis
Molecular Function
- nucleic acid binding
- metalloendopeptidase activity
- metal ion binding
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268070
- Coding exons
- 22
- Length
- 370417
- Individuals with no LoFs
- 125674
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000294
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.39 | 728 | 630 | 1.16 | 0.0000434 | 7044 |
| Missense (PolyPhen) | 337 | 307.36 | 1.0964 | 3444 | ||
| Synonymous | -4.69 | 372 | 273 | 1.36 | 0.0000215 | 2186 |
| Loss of Function | 3.28 | 34 | 61.9 | 0.549 | 0.00000368 | 635 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00046 | 0.00043 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00038 | 0.00038 | rare |
| South Asian | 0.00027 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Weill-Marchesani syndrome 4 (WMS4) [MIM:613195]: An autosomal recessive syndrome characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia and short stature. Brachydactyly and decreased joint flexibility are present in some patients. {ECO:0000269|PubMed:19836009, ECO:0000269|PubMed:22486325, ECO:0000269|PubMed:24940034}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.514
- RVIS EVS
- -2.27
- RVIS percentile EVS
- 1.26
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 | High |
| Cancer | High | Medium | High |