ADAMTS16

Chr 5

ADAM metallopeptidase with thrombospondin type 1 motif 16

Also known as: ADAMTS16s

NCBI Gene: 170690ENSG00000145536UniProt: Q8TE57

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 inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

321
ClinVar variants
116
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADAMTS16
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
116 Pathogenic / Likely Pathogenic· 188 VUS of 321 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.000
Z-score 5.26
OE 0.29 (0.20–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.41Z-score
OE missense 0.96 (0.90–1.02)
682 obs / 712.6 exp
Tolerant

Mild missense constraint

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.0.29 (0.20–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.90–1.02)
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.1.10
0≤1.21.6
LoF obs/exp: 19 / 64.7Missense obs/exp: 682 / 712.6Syn Z: -1.32

ClinVar Variant Classifications

321 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic114
Likely Pathogenic2
VUS188
Likely Benign16
Benign1
114
Pathogenic
2
Likely Pathogenic
188
VUS
16
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
114
0
114
Likely Pathogenic
0
0
2
0
2
VUS
0
183
5
0
188
Likely Benign
0
6
3
7
16
Benign
0
1
0
0
1
Total01901247321

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAMTS16 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.
Lin Y et al.·Circulation
2024
ADAMTS16 drives epithelial-mesenchymal transition and metastasis through a feedback loop upon TGF-β1 activation in lung adenocarcinoma.
Xiao L et al.·Cell Death Dis
2024
ADAM metallopeptidase with thrombospondin type 1 motif 16 is a potential marker for prognosis in clear cell renal cell carcinoma.
Bai C et al.·Pathol Int
2023
The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.
Li T et al.·Int J Mol Sci
2022
Genome-wide association study identifying novel risk variants associated with glycaemic traits in the continental African AWI-Gen cohort.
Chebii VJ et al.·Diabetologia
2025Cohort
Unravelling morphoea aetiopathogenesis by next-generation sequencing of paired skin biopsies.
Saracino AM et al.·Arch Dermatol Res
2023
Positional identification of variants of Adamts16 linked to inherited hypertension.
Joe B et al.·Hum Mol Genet
2009
Genetic contributions to urgency urinary incontinence in women.
Richter HE et al.·J Urol
2015
Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus.
Cipriani V et al.·Sci Rep
2017
Metalloproteinase gene expression correlates with clinical outcome in Dupuytren's disease.
Johnston P et al.·J Hand Surg Am
2008
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