ADAMTS9

Chr 3

ADAM metallopeptidase with thrombospondin type 1 motif 9

NCBI Gene: 56999ENSG00000163638UniProt: Q9P2N4

Cleaves the large aggregating proteoglycans, aggrecan (at the '1838-Glu-|-Ala-1839' site) and versican (at the '1428-Glu-|-Ala-1429' site). Has a protease-independent function in promoting the transport from the endoplasmic reticulum to the Golgi apparatus of a variety of secretory cargos

548
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADAMTS9
🧬
Gene-Disease Validity (ClinGen)
ciliopathy · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 324 VUS of 548 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.
0.39LOEUF
pLI 0.000
Z-score 7.13
OE 0.29 (0.22–0.39)
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.
0.95Z-score
OE missense 0.92 (0.87–0.97)
1030 obs / 1119.9 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 (0.22–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.87–0.97)
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.1.19
0≤1.21.6
LoF obs/exp: 35 / 118.9Missense obs/exp: 1030 / 1119.9Syn Z: -3.09

ClinVar Variant Classifications

548 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS324
Likely Benign93
Benign114
Conflicting6
10
Pathogenic
1
Likely Pathogenic
324
VUS
93
Likely Benign
114
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
1
0
0
0
1
VUS
3
313
7
1
324
Likely Benign
0
11
31
51
93
Benign
0
13
84
17
114
Conflicting
—6
Total433713269548

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAMTS9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ADAMTS9-related nephronophthisis related ciliopathy

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Dual Role of ADAMTS9-AS1 in Various Human Cancers: Molecular Pathogenesis and Clinical Implications.
He H et al.·Anticancer Agents Med Chem
2025Review
Cleavage of the Meckel-Gruber syndrome protein TMEM67 by ADAMTS9 uncouples Wnt signaling and ciliogenesis.
Ahmed M et al.·Nat Commun
2025
ADAMTS9-AS2 and CADM2 expression and association with the prognosis in esophageal squamous cell carcinoma.
Shen FF et al.·Biomark Med
2020
LncRNA ADAMTS9-AS1 knockdown suppresses cell proliferation and migration in glioma through downregulating Wnt/β-catenin signaling pathway.
Zhou C et al.·Bosn J Basic Med Sci
2022
ADAMTS9-AS2 Disrupts Docetaxel-Resistance in Castration-Resistant Prostate Cancer via Stemness Suppression and Ferroptosis Induction.
Liu J et al.·Adv Sci (Weinh)
2026
ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations.
Graae AS et al.·Diabetes
2019
Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study.
Boesgaard TW et al.·PLoS One
2009Meta-analysis
ADAMTS9-AS2: a potential diagnostic and prognostic hallmark in prostate cancer.
He L et al.·J BUON
2021
N6-methyladenosine-mediated overexpression of long noncoding RNA ADAMTS9-AS2 triggers neuroblastoma differentiation via regulating LIN28B/let-7/MYCN signaling.
Liu Y et al.·JCI Insight
2023
An integrated approach for key gene selection and cancer phenotype classification: Improving diagnosis and prediction.
Rahaman MM et al.·Comput Biol Med
2025
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