PSTPIP2

Chr 18

proline-serine-threonine phosphatase interacting protein 2

Also known as: MAYP

NCBI Gene: 9050 ENSG00000152229 UniProt: Q9H939 OMIM: 616046

This protein binds to F-actin and regulates the actin cytoskeleton. Mutations cause camptodactyly-arthropathy-coxa vara-pericarditis syndrome, an autoinflammatory disorder with skeletal abnormalities and pericarditis, inherited in an autosomal recessive pattern. The gene shows moderate tolerance to loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be located in cytoskeleton; cytosol; and membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.57

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.003

Z-score 3.38

OE 0.33 (0.20–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.14Z-score

OE missense 0.76 (0.66–0.88)

137 obs / 180.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.20–0.57)

0≤0.351.4

Missense OE?0.76 (0.66–0.88)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 10 / 29.9Missense obs/exp: 137 / 180.0Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in PSTPIP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

373 rare PASS variants

Rare truncating (LoF)

1 in 2,300

57 rare PASS variants

Rare synonymous (reference)

1 in 270

112 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PSTPIP2. 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 480	1 in 1,900
South Asian	~43k	1 in 250	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 130	1 in 5,900
European (Finnish)	~27k	1 in 1,200	1 in 4,400
Admixed American	~22k	1 in 180	1 in 2,000
African / African American	~21k	1 in 150	1 in 2,800
East Asian	~20k	1 in 140	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,884	1 in 180	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.