PRICKLE2

Chr 3

prickle planar cell polarity protein 2

NCBI Gene: 166336ENSG00000163637UniProt: Q7Z3G6

Is involved in the organization and maintenance of axon initial segment (AIS) architecture, likely cooperating with IGSF9B to regulate ANK3/ANKG localization to AIS (By similarity). By binding to and regulating ANK3/ANKG, it modulates its ability to bundle microtubules, a crucial mechanism for establishing neuronal polarity and AIS formation (By similarity). During early embryonic development, has a role in blastocyst formation, likely controlling the redistribution of the microtubule network during embryo compaction and the establishment of apical/basal cell polarity (By similarity)

576
ClinVar variants
15
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PRICKLE2
🧬
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.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 338 VUS of 576 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.72Z-score
OE missense 0.78 (0.72–0.85)
396 obs / 504.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.07–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.72–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 5 / 38.0Missense obs/exp: 396 / 504.9Syn Z: -0.38

ClinVar Variant Classifications

576 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic3
VUS338
Likely Benign174
Benign31
Conflicting18
12
Pathogenic
3
Likely Pathogenic
338
VUS
174
Likely Benign
31
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
11
0
12
Likely Pathogenic
1
2
0
0
3
VUS
2
281
51
4
338
Likely Benign
0
2
31
141
174
Benign
0
0
23
8
31
Conflicting
—18
Total4285116153576

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Decoding Epilepsy: Prickle2 and Multifaceted Molecular Pathway Connections.
Liu Y et al.·Curr Pharm Des
2025Review
PRICKLE2 revisited-further evidence implicating PRICKLE2 in neurodevelopmental disorders.
Bayat A et al.·Eur J Hum Genet
2021Case report
Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction.
Sowers LP et al.·Mol Psychiatry
2013
3p interstitial deletion including PRICKLE2 in identical twins with autistic features.
Okumura A et al.·Pediatr Neurol
2014Case report
Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population.
Turkdogan D et al.·Int J Neurosci
2023
Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing.
Rim JH et al.·BMC Med Genomics
2018
Mutations in prickle orthologs cause seizures in flies, mice, and humans.
Tao H et al.·Am J Hum Genet
2011
Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase.
Paemka L et al.·PLoS Genet
2015
A Genetic Variant in FIGN Gene Reduces the Risk of Congenital Heart Disease in Han Chinese Populations.
Wang D et al.·Pediatr Cardiol
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools