ANGPT1

Chr 8AD

angiopoietin 1

Also known as: AGP1, AGPT, AGPT-1, ANG1, HAE5

NCBI Gene: 284ENSG00000154188UniProt: Q15389OMIM: 601667

This gene encodes a secreted glycoprotein that belongs to the angiopoietin family. Members of this family play important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Mutations in this gene are associated with hereditary angioedema. [provided by RefSeq, Aug 2020]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.341 OMIM phenotype
Clinical Summary— ANGPT1
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Gene-Disease Validity (ClinGen)
primary congenital glaucoma · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
182 VUS of 335 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — ANGPT1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.34LOEUF
pLI 0.952
Z-score 4.12
OE 0.15 (0.07–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.30Z-score
OE missense 0.77 (0.69–0.87)
202 obs / 261.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.15 (0.07–0.34)
0≤0.351.4
Missense OE?0.77 (0.69–0.87)
0≤0.61.4
Synonymous OE?0.93
0≤1.21.6
LoF obs/exp: 4 / 27.2Missense obs/exp: 202 / 261.2Syn Z: 0.51

This gene — mechanism propensity

DN
0.5772th %ile
GOF
0.5072th %ile
LOF
0.50top 25%

The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · LOEUF 0.34

Literature Evidence

LOFPresent data show that in a heterozygous state the p.A119S substitution results in a pathogenic loss of function of the protein due to a mechanism of haploinsufficiency.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 30689269 ↗

ClinVar Variant Classifications

335 submitted variants in ClinVar

ClinVar

Classification Summary

VUS182
Likely Benign112
Benign26
Conflicting1
182
VUS
112
Likely Benign
26
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
12
159
11
0
182
Likely Benign
0
0
42
70
112
Benign
0
1
23
2
26
Conflicting
—1
Total121607672321

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap ANGPT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

ANGPT1 · protein map & ClinVar variants

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

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