ANGPT2

Chr 8AD

angiopoietin 2

Also known as: AGPT2, ANG2, LMPHM10

NCBI Gene: 285ENSG00000091879UniProt: O15123

This gene belongs to the angiopoietin family of growth factors. The protein encoded by this gene is an antagonist of angiopoietin 1, and both angiopoietin 1 and angiopoietin 2 are ligands for the endothelial TEK receptor tyrosine kinase. Angiopoietin 2 is upregulated in multiple inflammatory diseases and is implicated in the direct control of inflammation-related signaling pathways. The encoded protein affects angiogenesis during embryogenesis and tumorigenesis, disrupts the vascular remodeling ability of angiopoietin 1, and may induce endothelial cell apoptosis. This gene serves a prognostic biomarker for acute respiratory distress syndrome. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

Lymphatic malformation 10MIM #619369
AD
3
Active trials
120
Pathogenic / LP
307
ClinVar variants
97
Pubs (1 yr)
-0.5
Missense Z
0.38
LOEUF
Clinical Summary— ANGPT2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
120 Pathogenic / Likely Pathogenic· 113 VUS of 307 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.832
Z-score 4.02
OE 0.18 (0.09–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.53Z-score
OE missense 1.09 (0.99–1.20)
298 obs / 273.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.18 (0.09–0.38)
0≤0.351.4
Missense OE1.09 (0.99–1.20)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 5 / 27.9Missense obs/exp: 298 / 273.5Syn Z: -2.15
DN
DN
0.6259th %ile
GOF
0.5857th %ile
LOF
0.4136th %ile

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

DNprediction above median · 1 literature citation

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.

Literature Evidence

DNFunctional analyses revealed three missense mutations that resulted in decreased ANGPT2 secretion and inhibited the secretion of wild-type (WT)-ANGPT2, suggesting that they have a dominant-negative effect on ANGPT2 signaling.PMID:32908006

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

ClinVar Variant Classifications

307 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic113
Likely Pathogenic7
VUS113
Likely Benign45
Benign22
Conflicting7
113
Pathogenic
7
Likely Pathogenic
113
VUS
45
Likely Benign
22
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
111
0
113
Likely Pathogenic
2
0
5
0
7
VUS
1
84
27
1
113
Likely Benign
0
4
21
20
45
Benign
0
5
7
10
22
Conflicting
—7
Total39517131307

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

View in ClinVar →

ANGPT2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ANGPT2-related non-immune hydrops fetalis

limited
ARLoss Of FunctionDecreased Gene Product Level
Dev. Disorders
G2P ↗
frameshift variant NMD triggering

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

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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