PRICKLE2

Chr 3

prickle planar cell polarity protein 2

Also known as: EPM5

The protein regulates axon initial segment architecture by controlling ANK3/ANKG localization and microtubule bundling, which is crucial for establishing neuronal polarity. Mutations cause progressive myoclonic epilepsy type 5 with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.28
Clinical SummaryPRICKLE2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.995
Z-score 4.96
OE 0.13 (0.070.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.72Z-score
OE missense 0.78 (0.720.85)
396 obs / 504.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.070.28)
00.351.4
Missense OE0.78 (0.720.85)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 5 / 38.0Missense obs/exp: 396 / 504.9Syn Z: -0.38
DN
0.5081th %ile
GOF
0.4875th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PRICKLE2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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