ADAMTS17

Chr 15AR

ADAM metallopeptidase with thrombospondin type 1 motif 17

Also known as: WMS4

NCBI Gene: 170691ENSG00000140470UniProt: Q8TE56

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]

Primary Disease Associations & Inheritance

Weill-Marchesani 4 syndrome, recessiveMIM #613195
AR
UniProtWeill-Marchesani syndrome 4
420
ClinVar variants
67
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADAMTS17
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 159 VUS of 420 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.73LOEUF
pLI 0.000
Z-score 3.28
OE 0.55 (0.42–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.39Z-score
OE missense 1.16 (1.09–1.23)
728 obs / 629.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.42–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.16 (1.09–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.36
0≤1.21.6
LoF obs/exp: 34 / 61.9Missense obs/exp: 728 / 629.9Syn Z: -4.69

ClinVar Variant Classifications

420 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic15
VUS159
Likely Benign189
Benign5
52
Pathogenic
15
Likely Pathogenic
159
VUS
189
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
1
41
0
52
Likely Pathogenic
10
0
5
0
15
VUS
1
147
10
1
159
Likely Benign
0
1
79
109
189
Benign
0
0
3
2
5
Total21149138112420

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ADAMTS17 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ADAMTS17-related Weill-Marchesani-like syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Weill-Marchesani 4 syndrome, recessive

MIM #613195

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ADAMTS17
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Characteristics and genotype-phenotype correlations in ADAMTS17 mutation-related Weill-Marchesani syndrome.
Guo D et al.·Exp Eye Res
2023
A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features.
Evans DR et al.·Sci Rep
2020
Weill-Marchesani syndrome: natural history and genotype-phenotype correlations from 18 news cases and review of literature.
Marzin P et al.·J Med Genet
2024Review
A novel ADAMTS17 variant that causes Weill-Marchesani syndrome 4 alters fibrillin-1 and collagen type I deposition in the extracellular matrix.
Karoulias SZ et al.·Matrix Biol
2020
Alternative splicing of the metalloprotease ADAMTS17 spacer regulates secretion and modulates autoproteolytic activity.
Balic Z et al.·FASEB J
2021
Genotype-phenotype association of PITX2 and FOXC1 in Axenfeld-Rieger syndrome.
Zhou L et al.·Exp Eye Res
2023Review
Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature.
Morales J et al.·Am J Hum Genet
2009
A common variant rs2054564 in ADAMST17 is associated with susceptibility to lumbar spondylosis.
Taniguchi Y et al.·Sci Rep
2023
Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics.
Dubail J et al.·Matrix Biol
2015Review
Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort.
Liu Y et al.·Hum Genomics
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools