PRICKLE1

Chr 12AR

prickle planar cell polarity protein 1

Also known as: EPM1B, RILP

NCBI Gene: 144165ENSG00000139174UniProt: Q96MT3

This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway. The encoded protein localizes to the nuclear membrane and has been implicated in the nuclear trafficking of the transcription repressors REST/NRSF and REST4. Mutations in this gene have been linked to progressive myoclonus epilepsy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Epilepsy, progressive myoclonic 1BMIM #612437
AR
UniProtNeural tube defects
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PRICKLE1
⚡
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.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.13LOEUF
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?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.
1.83Z-score
OE missense 0.76 (0.69–0.83)
348 obs / 458.5 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.0.03 (0.01–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.69–0.83)
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.0.91
0≤1.21.6
LoF obs/exp: 1 / 36.8Missense obs/exp: 348 / 458.5Syn Z: 0.90

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Epilepsy, progressive myoclonic 1B

MIM #612437

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Overcoming Clinical Resistance to EZH2 Inhibition Using Rational Epigenetic Combination Therapy.
Kazansky Y et al.·Cancer Discov
2024
PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia.
Jiang D et al.·J Transl Med
2021
A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome.
Bassuk AG et al.·Am J Hum Genet
2008
The genomic and clinical landscape of fetal akinesia.
Pergande M et al.·Genet Med
2020
Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.
Lu Y et al.·Gastroenterology
2019Meta-analysis
A very rare form of autosomal dominant progressive myoclonus epilepsy caused by a novel variant in the PRICKLE1 gene.
Algahtani H et al.·Seizure
2019Case report
AutoCaSc: Prioritizing candidate genes for neurodevelopmental disorders.
Lieberwirth JK et al.·Hum Mutat
2022
SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure.
Dibbens LM et al.·Ann Neurol
2009
A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects.
Juriloff DM et al.·Birth Defects Res A Clin Mol Teratol
2012Review
PRICKLE1-related early onset epileptic encephalopathy.
Mastrangelo M et al.·Am J Med Genet A
2018Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of PRICKLE1 leads to subfertility, aberrant extracellular matrix and abnormal myometrial architecture in mice.
Roberts ER et al.·Reproduction
2025
Loss of PRICKLE1 leads to abnormal endometrial epithelial architecture, decreased embryo implantation, and reduced fertility in mice.
Roberts ER et al.·PNAS Nexus
2025🔓 Open Access
Prickle1-driven basement membrane deposition of the iPSC-derived embryoid bodies is separable from the establishment of apicobasal polarity.
Guo D et al.·Cell Prolif
2024🔓 Open Access
PRICKLE1 gene methylation and abnormal transcription in Chinese patients with ankylosing spondylitis.
Zhou T et al.·Immunobiology
2023Cohort
Wnt signaling pathway-related gene PRICKLE1 is a prognostic biomarker for esophageal squamous cell carcinoma.
He J et al.·Front Oncol
2022🔓 Open Access
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