PLEKHO2

Chr 15

pleckstrin homology domain containing O2

Also known as: PLEKHQ1, PP1628, pp9099

NCBI Gene: 80301 ENSG00000241839 UniProt: Q8TD55

Predicted to be involved in macrophage apoptotic process. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Jul 2025]

Research

Predicted to be involved in macrophage apoptotic process. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Jul 2025]

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

0.62

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.034

Z-score 2.77

OE 0.32 (0.17–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.25Z-score

OE missense 0.96 (0.87–1.06)

269 obs / 280.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.17–0.62)

0≤0.351.4

Missense OE?0.96 (0.87–1.06)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 6 / 19.0Missense obs/exp: 269 / 280.6Syn Z: 0.05

Background carrier burden — how many people carry a rare variant somewhere in PLEKHO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

599 rare PASS variants

Rare truncating (LoF)

1 in 4,700

54 rare PASS variants

Rare synonymous (reference)

1 in 200

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLEKHO2. 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 130	1 in 5,500
South Asian	~43k	1 in 88	1 in 5,400
Remaining (unassigned)	~30k	1 in 58	1 in 4,300
European (Finnish)	~27k	1 in 180	≈ 1 in 6,600
Admixed American	~22k	1 in 110	none seen
African / African American	~21k	1 in 91	1 in 2,100
East Asian	~20k	1 in 160	1 in 3,100
Ashkenazi Jewish	~13k	1 in 870	≈ 1 in 2,600
Middle Eastern	~2,884	1 in 73	≈ 1 in 960

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.