PLEKHA2

Chr 8

pleckstrin homology domain containing A2

Also known as: TAPP2

NCBI Gene: 59339 ENSG00000169499 UniProt: Q9HB19 OMIM: 607773

Enables fibronectin binding activity; laminin binding activity; and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in positive regulation of cell-matrix adhesion. Located in cytoplasm and membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

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

0.39

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.838

Z-score 3.74

OE 0.17 (0.08–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.08Z-score

OE missense 0.63 (0.55–0.72)

156 obs / 248.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.39)

0≤0.351.4

Missense OE?0.63 (0.55–0.72)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 23.6Missense obs/exp: 156 / 248.1Syn Z: -0.35

Background carrier burden — how many people carry a rare variant somewhere in PLEKHA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

452 rare PASS variants

Rare truncating (LoF)

1 in 2,700

64 rare PASS variants

Rare synonymous (reference)

1 in 150

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLEKHA2. 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 180	1 in 1,900
South Asian	~43k	1 in 130	1 in 4,200
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 15,000
European (Finnish)	~27k	1 in 270	≈ 1 in 13,000
Admixed American	~22k	1 in 120	≈ 1 in 22,000
African / African American	~21k	1 in 130	1 in 2,800
East Asian	~20k	1 in 160	none seen
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 320	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 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓