Human Gene Module / Chromosome 12 / PRICKLE1

PRICKLE1Prickle homolog 1 (Drosophila)

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 7
Rare Variants / Common Variants
8 / 0
Aliases
PRICKLE1, EPM1B,  RILP
Associated Syndromes
-
Chromosome Band
12q12
Associated Disorders
ID
Relevance to Autism

Prickle1 +/- mice were shown to exhibit ASD-like behaviors, including altered social behaviors and disrupted circadian rhythms; PRICKLE1 was also shown to interact with Synapsin-1a, a gene product of the ASD-associated gene SYN1 (Paemka et al., 2013).

Molecular Function

This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway and is involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.. Defects in this gene are associated with epilepsy, progressive myoclonic 1B (EPM1B) [MIM:612437] and neural tube defects (NTD) [MIM:182940].

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PRICKLE1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome Bassuk AG , et al. (2008) No -
2 Support Mutations in prickle orthologs cause seizures in flies, mice, and humans Tao H , et al. (2011) No ID
3 Primary PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders Paemka L , et al. (2013) No -
4 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
5 Support - Ban Y et al. (2022) No ASD
6 Support - Zhou X et al. (2022) Yes -
7 Support - Chen Y et al. (2022) No -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1444G>A p.Asp482Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.431G>A p.Arg144His missense_variant Unknown - Unknown 21276947 Tao H , et al. (2011)
c.1414T>C p.Tyr472His missense_variant Unknown - Unknown 21276947 Tao H , et al. (2011)
c.2367G>C p.Gln789His missense_variant Familial Maternal Multiplex 23999528 Toma C , et al. (2013)
c.311G>A p.Arg104Gln missense_variant Familial Both parents Multiplex 18976727 Bassuk AG , et al. (2008)
c.311G>A p.Arg104Gln missense_variant Familial Both parents Extended multiplex 18976727 Bassuk AG , et al. (2008)
c.169G>C p.Val57Leu missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
c.553G>A p.Glu185Lys missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Prickle1 +/- mice were shown to exhibit ASD-like behaviors, including altered social behaviors and disrupted circadian rhythms; PRICKLE1 was also shown to interact with Synapsin-1a, a gene product of the ASD-associated gene SYN1 (Paemka et al., 2013). Potentially damaging missense variants in PRICKLE1 have been observed in affected siblings from ASD multiplex families (PMIDs 24410847, 23999528). Homozygous variants in PRICKLE1 are the cause of progressive myoclonic epilepsy-1B (EPM1B; OMIM 612437).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Prickle1 +/- mice were shown to exhibit ASD-like behaviors, including altered social behaviors and disrupted circadian rhythms; PRICKLE1 was also shown to interact with Synapsin-1a, a gene product of the ASD-associated gene SYN1 (Paemka et al., 2013). Potentially damaging missense variants in PRICKLE1 have been observed in affected siblings from ASD multiplex families (PMIDs 24410847, 23999528). Homozygous variants in PRICKLE1 are the cause of progressive myoclonic epilepsy-1B (EPM1B; OMIM 612437).

Reports Added
[New Scoring Scheme]
7/1/2015
icon
3

Increased from to 3

Description

Prickle1 +/- mice were shown to exhibit ASD-like behaviors, including altered social behaviors and disrupted circadian rhythms; PRICKLE1 was also shown to interact with Synapsin-1a, a gene product of the ASD-associated gene SYN1 (Paemka et al., 2013). Potentially damaging missense variants in PRICKLE1 have been observed in affected siblings from ASD multiplex families (PMIDs 24410847, 23999528). Homozygous variants in PRICKLE1 are the cause of progressive myoclonic epilepsy-1B (EPM1B; OMIM 612437).

Krishnan Probability Score

Score 0.49163773652979

Ranking 5311/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99196685869644

Ranking 1712/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.93956216013068

Ranking 14254/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 15

Ranking 132/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.36473046498368

Ranking 1849/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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