ADAMTS9

Chr 3

ADAM metallopeptidase with thrombospondin type 1 motif 9

This metalloproteinase cleaves large proteoglycans including aggrecan and versican, and promotes protein transport from the endoplasmic reticulum to the Golgi apparatus. Mutations cause Winchester syndrome, a rare autosomal recessive disorder characterized by progressive osteolysis, corneal opacities, and skin abnormalities. The gene is highly constrained against loss-of-function variants, indicating that complete loss of function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.39
Clinical SummaryADAMTS9
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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.
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ClinVar Variants
149 VUS of 200 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.000
Z-score 7.13
OE 0.29 (0.220.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.95Z-score
OE missense 0.92 (0.870.97)
1030 obs / 1119.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.220.39)
00.351.4
Missense OE0.92 (0.870.97)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 35 / 118.9Missense obs/exp: 1030 / 1119.9Syn Z: -3.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongADAMTS9-related nephronophthisis related ciliopathyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6841th %ile
GOF
0.5366th %ile
LOF
0.3552th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

VUS149
Likely Benign24
Benign3
Conflicting1
149
VUS
24
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
147
1
0
149
Likely Benign
0
3
6
15
24
Benign
0
1
1
1
3
Conflicting
1
Total1151816177

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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