PRICKLE2

Chr 3

prickle planar cell polarity protein 2

Also known as: EPM5

NCBI Gene: 166336 ENSG00000163637 OMIM: 608501

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a homolog of Drosophila prickle. The exact function of this gene is not known, however, studies in mice suggest that it may be involved in seizure prevention. Mutations in this gene are associated with progressive myoclonic epilepsy type 5. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— PRICKLE2

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.995

Z-score 4.96

OE 0.13 (0.07–0.28)

Highly constrained

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

Missense Constraint?

1.72Z-score

OE missense 0.78 (0.72–0.85)

396 obs / 504.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.28)

0≤0.351.4

Missense OE?0.78 (0.72–0.85)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 5 / 38.0Missense obs/exp: 396 / 504.9Syn Z: -0.38

This gene — mechanism propensity

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.