PRICKLE2
protein-codingprickle planar cell polarity protein 2, the group of Prickle planar cell polarity proteins|LIM domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~353.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: ClinGen
*PRICKLE2* was first reported in relation to autosomal dominant complex neurodevelopmental disorder [MONDO:0100038] in 2011. (Tao et al., PMID: 21276947). At the time of this curation, there were no other single-gene disorders associated with this gene. This curation is based on this disease entity only. Evidence supporting this gene-disease relationship includes case-level data. 4 variants (missense, nonsense and frameshift) that have been reported in 4 probands in 3 publications (PMIDs: 21276947, 29390993, 34092786) are included in this curation. The mechanism of pathogenicity appears to be LOF, but it is still unclear. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on the meeting date 12/06/2022 (SOP Version 9).
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PRICKLE2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198859.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 162 | 2 | 169 | ||
| missense | 3 | 333 | 6 | 342 | ||
| nonsense | 1 | 5 | 6 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | 4 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 5 | 345 | 168 | 2 | 521 |
Highest pathogenic variant AF is 0.00001486882
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_942559.1 | 7 | MANE Select | |
| Ensembl | ENSP00000492363.1 | 7 | MANE Select | |
| RefSeq | NP_001357457.1 | 7 | Standard | |
| Ensembl | ENSP00000295902.7 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| prickle2b | Danio rerio | Structure: retinal inner plexiform layer Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Wnt signaling pathway - Homo sapiens (human)
- Wnt Signaling Pathway
Biological Process
- Wnt signaling pathway, planar cell polarity pathway
Molecular Function
- zinc ion binding
Cellular Component
- cytoplasm
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295902
- Coding exons
- 7
- Length
- 351610
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.72 | 396 | 505 | 0.784 | 0.0000332 | 5585 |
| Missense (PolyPhen) | 60 | 129.96 | 0.46168 | 1440 | ||
| Synonymous | -0.383 | 209 | 202 | 1.03 | 0.0000134 | 1614 |
| Loss of Function | 4.96 | 5 | 38.0 | 0.132 | 0.00000245 | 399 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.0756
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.578
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |