ADAMTS19

Chr 5AR

ADAM metallopeptidase with thrombospondin type 1 motif 19

Also known as: CVDP2

NCBI Gene: 171019ENSG00000145808UniProt: Q8TE59

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family 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 protein encoded by this gene has high sequence similarity to the protein encoded by ADAMTS16, another family member. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cardiac valvular dysplasia 2MIM #620067
AR
224
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADAMTS19
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 180 VUS of 224 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.
0.54LOEUF
pLI 0.000
Z-score 4.54
OE 0.38 (0.28–0.54)
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.
2.10Z-score
OE missense 0.76 (0.70–0.82)
451 obs / 595.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.38 (0.28–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.70–0.82)
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.1.01
0≤1.21.6
LoF obs/exp: 24 / 62.9Missense obs/exp: 451 / 595.2Syn Z: -0.09

ClinVar Variant Classifications

224 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic4
VUS180
Likely Benign16
Benign4
20
Pathogenic
4
Likely Pathogenic
180
VUS
16
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
17
0
20
Likely Pathogenic
2
0
2
0
4
VUS
1
168
11
0
180
Likely Benign
0
8
3
5
16
Benign
0
1
2
1
4
Total6177356224

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAMTS19 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ADAMTS19-related cardiac valvular dysplasia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
splice region variantstop gainedwhole partial gene deletion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cardiac valvular dysplasia 2

MIM #620067

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ADAMTS proteases in cardiovascular physiology and disease.
Santamaria S et al.·Open Biol
2020Review
Genetics of aortic valve disease.
Ackah RL et al.·Curr Opin Cardiol
2023Review
Identification and Validation of Prognostic Markers for Endometriosis-Associated Ovarian Cancer.
Yang H et al.·Int J Med Sci
2024
Loss of ADAMTS19 causes progressive non-syndromic heart valve disease.
Wünnemann F et al.·Nat Genet
2020
ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype.
Massadeh S et al.·Clin Genet
2020
Genomic Landscape and Mutational Spectrum of ADAMTS Family Genes in Mendelian Disorders Based on Gene Evidence Review for Variant Interpretation.
Rim JH et al.·Biomolecules
2020Review
Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations.
Fonseca DJ et al.·Fertil Steril
2015
Comparison of Serum A Disintegrin and Metalloproteinase with Thrombospondin Motifs-19 Levels in Different Fertility Situations: Could It Be a Serum Marker of Ovarian Function and Oocyte Pool?
Ersoy E et al.·Gynecol Obstet Invest
2019
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