PRICKLE1

Chr 12AR

prickle planar cell polarity protein 1

Also known as: EPM1B, RILP

NCBI Gene: 144165ENSG00000139174UniProt: Q96MT3OMIM: 608500

The protein functions as a nuclear receptor involved in planar cell polarity signaling that controls neural tube closure and convergent extension during development, and is necessary for nuclear localization of the transcription repressor REST. Biallelic mutations cause progressive myoclonic epilepsy 1B with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.13), indicating that heterozygous loss-of-function variants are likely benign.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.131 OMIM phenotype
Clinical Summary— PRICKLE1
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Gene-Disease Validity (ClinGen)
epilepsy · ADDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

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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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ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 67 VUS of 147 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 5.47
OE 0.03 (0.01–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.83Z-score
OE missense 0.76 (0.69–0.83)
348 obs / 458.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.01–0.13)
0≤0.351.4
Missense OE0.76 (0.69–0.83)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 1 / 36.8Missense obs/exp: 348 / 458.5Syn Z: 0.90
DN
0.4587th %ile
GOF
0.5170th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.13

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

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS67
Likely Benign52
Benign7
Conflicting10
5
Pathogenic
1
Likely Pathogenic
67
VUS
52
Likely Benign
7
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
4
0
5
Likely Pathogenic
0
1
0
0
1
VUS
1
56
8
2
67
Likely Benign
0
1
11
40
52
Benign
0
3
1
3
7
Conflicting
—10
Total1622445142

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

View in ClinVar →

Protein Context — Lollipop Plot

PRICKLE1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients