AMOTL2

Chr 3

angiomotin like 2

Also known as: LCCP

NCBI Gene: 51421 ENSG00000114019 UniProt: Q9Y2J4 OMIM: 614658

Angiomotin is a protein that binds angiostatin, a circulating inhibitor of the formation of new blood vessels (angiogenesis). Angiomotin mediates angiostatin inhibition of endothelial cell migration and tube formation in vitro. The protein encoded by this gene is related to angiomotin and is a member of the motin protein family. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.155

Z-score 4.24

OE 0.25 (0.15–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.08Z-score

OE missense 0.99 (0.92–1.07)

483 obs / 487.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.15–0.43)

0≤0.351.4

Missense OE?0.99 (0.92–1.07)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 36.7Missense obs/exp: 483 / 487.7Syn Z: 0.35

Background carrier burden — how many people carry a rare variant somewhere in AMOTL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,130 rare PASS variants

Rare truncating (LoF)

1 in 2,300

98 rare PASS variants

Rare synonymous (reference)

1 in 110

476 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AMOTL2. 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 64	1 in 2,300
South Asian	~43k	1 in 33	1 in 3,700
Remaining (unassigned)	~30k	1 in 35	1 in 5,000
European (Finnish)	~27k	1 in 130	1 in 3,800
Admixed American	~22k	1 in 32	1 in 1,900
African / African American	~21k	1 in 41	≈ 1 in 4,500
East Asian	~20k	1 in 36	1 in 800
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 45	none seen

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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓