ADAMTS17

Chr 15

ADAM metallopeptidase with thrombospondin type 1 motif 17

Also known as: WMS4

NCBI Gene: 170691 ENSG00000140470 UniProt: Q8TE56

The protein is a metalloproteinase that cleaves extracellular matrix components and is highly intolerant to loss-of-function variants (LOEUF 0.732). Biallelic mutations cause Weill-Marchesani syndrome type 4, characterized by ocular abnormalities including ectopia lentis, spherophakia, glaucoma, and lenticular myopia, along with short stature. This follows autosomal recessive inheritance.

GeneReviews ResearchSummary from RefSeq, OMIM

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWeill-Marchesani syndrome 4

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.73

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ADAMTS17

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 3.28

OE 0.55 (0.42–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.39Z-score

OE missense 1.16 (1.09–1.23)

728 obs / 629.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.42–0.73)

0≤0.351.4

Missense OE?1.16 (1.09–1.23)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 34 / 61.9Missense obs/exp: 728 / 629.9Syn Z: -4.69

Background carrier burden — how many people carry a rare variant somewhere in ADAMTS17?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 23

1,840 rare PASS variants

Rare truncating (LoF)

1 in 790

234 rare PASS variants

Rare synonymous (reference)

1 in 38

834 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADAMTS17. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 31	1 in 730
South Asian	~43k	1 in 23	1 in 880
Remaining (unassigned)	~30k	1 in 23	1 in 1,200
European (Finnish)	~27k	1 in 65	1 in 910
Admixed American	~22k	1 in 27	1 in 1,200
African / African American	~21k	1 in 26	1 in 970
East Asian	~20k	1 in 27	1 in 520
Ashkenazi Jewish	~13k	1 in 100	≈ 1 in 3,800
Middle Eastern	~2,884	1 in 28	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 22 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 22.? see exons ↓