PRICKLE3

Chr XXLD

prickle planar cell polarity protein 3

Also known as: LMO6, LOAM, LOAS, Pk3

NCBI Gene: 4007ENSG00000012211UniProt: O43900OMIM: 300111

PRICKLE3 encodes a protein that regulates planar cell polarity during development and is required for proper assembly and function of mitochondrial ATP synthase (complex V). Mutations cause X-linked dominant Leber hereditary optic neuropathy or modify its severity, affecting mitochondrial energy production in retinal ganglion cells. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.478), suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
XLDLOEUF 0.481 OMIM phenotype
Clinical Summary— PRICKLE3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
76 unique Pathogenic / Likely Pathogenic· 97 VUS of 199 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.632
Z-score 3.04
OE 0.18 (0.08–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.19Z-score
OE missense 0.80 (0.72–0.90)
232 obs / 289.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.08–0.48)
0≤0.351.4
Missense OE0.80 (0.72–0.90)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 3 / 16.2Missense obs/exp: 232 / 289.0Syn Z: 0.89

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic74
Likely Pathogenic2
VUS97
Likely Benign3
Conflicting2
74
Pathogenic
2
Likely Pathogenic
97
VUS
3
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
74
0
74
Likely Pathogenic
0
0
2
0
2
VUS
1
88
8
0
97
Likely Benign
0
1
0
2
3
Benign
0
0
0
0
0
Conflicting
—2
Total189842178

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

View in ClinVar →

Protein Context — Lollipop Plot

PRICKLE3 · 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 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 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