ADAMTS16

Chr 5

ADAM metallopeptidase with thrombospondin type 1 motif 16

Also known as: ADAMTS16s

NCBI Gene: 170690ENSG00000145536UniProt: Q8TE57OMIM: 607510

This gene encodes a metalloproteinase with thrombospondin motifs that may regulate blood pressure and inhibit chondrosarcoma cell proliferation and migration. The gene is highly constrained against loss-of-function variants (pLI=0.0004, LOEUF=0.431), but no established Mendelian diseases have been definitively associated with ADAMTS16 mutations. Further research is needed to determine the clinical significance of variants in this gene.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.43
Clinical Summary— ADAMTS16
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
117 unique Pathogenic / Likely Pathogenic· 188 VUS of 343 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
0.41Z-score
OE missense 0.96 (0.90–1.02)
682 obs / 712.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.20–0.43)
0≤0.351.4
Missense OE0.96 (0.90–1.02)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 19 / 64.7Missense obs/exp: 682 / 712.6Syn Z: -1.32
DN
0.7229th %ile
GOF
0.5857th %ile
LOF
0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

343 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic115
Likely Pathogenic2
VUS188
Likely Benign17
Benign1
115
Pathogenic
2
Likely Pathogenic
188
VUS
17
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
1
0
1
0
2
VUS
0
183
5
0
188
Likely Benign
0
7
3
7
17
Benign
0
1
0
0
1
Total11911247323

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
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
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
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
Genetic biomarkers associated with pain flare and dexamethasone response following palliative radiotherapy in patients with painful bone metastases.
Furfari A et al.·Ann Palliat Med
2017Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients