ANGPTL2

Chr 9

angiopoietin like 2

Also known as: ARP2, HARP

NCBI Gene: 23452 ENSG00000136859 UniProt: Q9UKU9 OMIM: 605001

ANGPTL2 encodes a secreted glycoprotein that induces sprouting in endothelial cells and participates in blood vessel formation through autocrine and paracrine signaling. Mutations cause microcephaly-capillary malformation syndrome, an autosomal recessive disorder characterized by primary microcephaly and capillary malformations. The condition affects both brain development and the vascular system from early development.

OMIM ResearchSummary from RefSeq, UniProt

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. ANGPTL2 protein is a secreted glycoprotein with homology to the angiopoietins and may exert a function on endothelial cells through autocrine or paracrine action. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.001

Z-score 2.81

OE 0.38 (0.23–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.20Z-score

OE missense 0.81 (0.73–0.90)

253 obs / 312.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.23–0.66)

0≤0.351.4

Missense OE?0.81 (0.73–0.90)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 9 / 23.8Missense obs/exp: 253 / 312.9Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in ANGPTL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

578 rare PASS variants

Rare truncating (LoF)

1 in 3,600

65 rare PASS variants

Rare synonymous (reference)

1 in 160

290 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANGPTL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 3,100
South Asian	~43k	1 in 110	≈ 1 in 20,000
Remaining (unassigned)	~30k	1 in 92	1 in 5,000
European (Finnish)	~27k	1 in 580	1 in 5,200
Admixed American	~22k	1 in 110	≈ 1 in 7,600
African / African American	~21k	1 in 75	≈ 1 in 9,300
East Asian	~20k	1 in 130	≈ 1 in 6,500
Ashkenazi Jewish	~13k	1 in 260	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓