ANGPTL1

Chr 1

angiopoietin like 1

Also known as: ANG3, ANGPT3, ARP1, AngY, UNQ162, dJ595C2.2

NCBI Gene: 9068 ENSG00000116194 UniProt: O95841 OMIM: 603874

Angiopoietins are members of the vascular endothelial growth factor family and the only known growth factors largely specific for vascular endothelium. Angiopoietin-1, angiopoietin-2, and angiopoietin-4 participate in the formation of blood vessels. The protein encoded by this gene is another member of the angiopoietin family that is widely expressed in adult tissues with mRNA levels highest in highly vascularized tissues. This protein was found to be a secretory protein that does not act as an endothelial cell mitogen in vitro. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.27

Clinical Summary— ANGPTL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

88 VUS of 95 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.63

OE 0.85 (0.58–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.48Z-score

OE missense 0.92 (0.82–1.02)

242 obs / 263.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.85 (0.58–1.27)

0≤0.351.4

Missense OE?0.92 (0.82–1.02)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 17 / 20.0Missense obs/exp: 242 / 263.9Syn Z: 0.02

This gene — mechanism propensity

0.7035th %ile

GOF

0.5660th %ile

LOF

0.3648th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

VUS88

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	88	0	88
Likely Benign	1	0	1
Benign	0	1	1
Total	89	1	90

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap ANGPTL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →