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PRICKLE1
prickle planar cell polarity protein 1
The PRICKLE1 gene codes for a protein that appears to be important for nervous system development and cellular organisation. The PRICKLE1 gene provides instructions for making the prickle homolog 1 protein.
PRICKLE1 is located on the long (q) arm of chromosome 12, at band 12q12. Arm ratio per GRCh38 - banding schematic.
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Overview
The PRICKLE1 gene, also known as prickle planar cell polarity protein 1, is involved in producing a protein essential for the proper development of the nervous system. Its exact mechanisms remain unclear, but research suggests it contributes to fundamental cellular processes, particularly those related to cell polarity and neuronal migration.
This gene is thought to be part of the noncanonical Wnt signalling pathway, a complex network that regulates the positioning of cellular components and the movement of nerve cells. Dysregulation of PRICKLE1 can have implications for neurological health.
What the gene does
The PRICKLE1 gene directs the synthesis of the prickle homolog 1 protein. This protein is believed to be a component of the noncanonical Wnt signalling pathway, which is vital during embryonic development [PMID:24726269]. This pathway helps to determine the internal arrangement of structures within cells (cell polarity) and guides the movement of nerve cells (neurons) as the nervous system forms.
Studies indicate that the prickle homolog 1 protein interacts with other proteins, including the RE1-silencing transcription factor (REST). REST is known to regulate several key genes in neurons by suppressing their activity. The prickle homolog 1 protein is thought to control REST by facilitating its transport out of the cell nucleus, thereby preventing REST from binding to DNA and inhibiting gene expression [PMID:24726269]. The precise contribution of this interaction to nervous system development remains an area of ongoing research.
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Chromosome location
The PRICKLE1 gene is situated on chromosome 12. Its specific genomic location is 12q12, which refers to the long arm (q) of chromosome 12, within region 12, band 12.
Protein structure
The prickle homolog 1 protein comprises 831 amino acids and features several distinct domains. At its N-terminus, it contains a PET domain (amino acids 14-122). Following this are three LIM zinc-binding domains: LIM zinc-binding 1 (amino acids 124-189), LIM zinc-binding 2 (amino acids 189-249), and LIM zinc-binding 3 (amino acids 249-313). Additionally, the protein contains several intrinsically disordered regions, specifically at amino acids 313-342, 663-688, and 763-831.
Key variants
Variations within the PRICKLE1 gene can alter the structure or function of the prickle homolog 1 protein. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions. Depending on their nature and location, such variants may impact the protein's ability to participate in crucial signalling pathways and cellular processes, potentially leading to health implications.
Sample of pathogenic variants
1 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1414T>C | p.Tyr472His | Pathogenic | - | Epilepsy, progressive myoclonic, 1B |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Mutations in the PRICKLE1 gene have been identified in individuals with PRICKLE1-related progressive myoclonus epilepsy with ataxia [PMID:24726269]. This condition is characterised by progressive neurological symptoms, including involuntary muscle jerks (myoclonus) and difficulties with coordination and balance (ataxia). At least three distinct mutations have been identified, each involving a single amino acid change in the prickle homolog 1 protein.
No disease links recorded for this gene in our reference set.
UK clinical status
Frequently asked questions
What is the function of the PRICKLE1 gene?
The PRICKLE1 gene produces the prickle homolog 1 protein, which is believed to be involved in the noncanonical Wnt signalling pathway. This pathway is important for establishing cell polarity and guiding the movement of nerve cells during development.
What conditions are associated with PRICKLE1 gene mutations?
Mutations in the PRICKLE1 gene have been linked to PRICKLE1-related progressive myoclonus epilepsy with ataxia, a neurological disorder characterised by muscle jerks and issues with coordination.
Where is the PRICKLE1 gene located?
The PRICKLE1 gene is found on chromosome 12, specifically at position 12q12. This location refers to a particular band on the long arm of chromosome 12.
References
- Tao H, Manak JR, Sowers L. Mutations in prickle orthologs cause seizures in flies, mice, and humans. American journal of human genetics. 2011. PMID: 21276947
- Bassuk AG, Wallace RH, Buhr A. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. American journal of human genetics. 2008. PMID: 18976727
- Shimojo M, Hersh LB. Characterization of the REST/NRSF-interacting LIM domain protein (RILP): localization and interaction with REST/NRSF. Journal of neurochemistry. 2006. PMID: 16417580
- Katoh M, Katoh M. Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle. International journal of molecular medicine. 2003. PMID: 12525887
- Shimojo M, Hersh LB. REST/NRSF-interacting LIM domain protein, a putative nuclear translocation receptor. Molecular and cellular biology. 2003. PMID: 14645515