ANGPT1

Chr 8AD

angiopoietin 1

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

This gene encodes angiopoietin-1, a secreted glycoprotein that activates the TEK/TIE2 receptor to regulate angiogenesis, endothelial cell survival and proliferation, blood vessel maturation and stability, and inhibits endothelial permeability. Mutations cause hereditary angioedema type 5 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.34), reflecting its essential role in vascular development and heart formation during embryogenesis.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Angioedema, hereditary, 5MIM #619361
AD
1
Active trials
57
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryANGPT1
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Gene-Disease Validity (ClinGen)
primary congenital glaucoma · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — ANGPT1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.952
Z-score 4.12
OE 0.15 (0.070.34)
Highly constrained

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

Missense Constraint
1.30Z-score
OE missense 0.77 (0.690.87)
202 obs / 261.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.070.34)
00.351.4
Missense OE0.77 (0.690.87)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 4 / 27.2Missense obs/exp: 202 / 261.2Syn Z: 0.51
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.PMID:30689269

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ANGPT1 · protein map & ClinVar variants

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

Clinical Literature
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