PRICKLE1

prickle planar cell polarity protein 1, the group of Prickle planar cell polarity proteins|LIM domain containing

Basic information

Region (hg38): 12:42456757-42590355

Links

ENSG00000139174

∙ NCBI:144165 ∙ OMIM:608500 ∙ HGNC:17019 ∙ Uniprot:Q96MT3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Unverricht-Lundborg syndrome (Supportive), mode of inheritance: AR
epilepsy, progressive myoclonic, 1B (Strong), mode of inheritance: AR
epilepsy (Disputed Evidence), mode of inheritance: AD
progressive myoclonus epilepsy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic, 1B	AD/AR	General	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	Neurologic	15634728; 15642921; 16376507; 18976727; 21276947
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRICKLE1 gene.

Epilepsy,_progressive_myoclonic,_1B (490 variants)
not_specified (156 variants)
not_provided (107 variants)
PRICKLE1-related_disorder (18 variants)
Self-limited_epilepsy_with_centrotemporal_spikes (3 variants)
Intellectual_disability (3 variants)
Fetal_akinesia_deformation_sequence_1 (1 variants)
Seizure (1 variants)
Inborn_genetic_diseases (1 variants)
Arthrogryposis_multiplex_congenita (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRICKLE1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153026.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	155 clinvar	2 clinvar	160
missense	1 clinvar	1 clinvar	323 clinvar	8 clinvar	3 clinvar	336
nonsense			3 clinvar			3
start loss			1			1
frameshift			9 clinvar			9
splice donor/acceptor (+/-2bp)						0
Total	1	1	339	163	5

Highest pathogenic variant AF is 0.000016108426

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRICKLE1	protein_coding	protein_coding	ENST00000455697	7	132018

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000961	125737	0	8	125745	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	348	458	0.759	0.0000268	5482
Missense in Polyphen		102	176.96	0.57641		2053
Synonymous	0.905	162	177	0.914	0.0000107	1552
Loss of Function	5.47	1	36.8	0.0271	0.00000197	445

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000121	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure. Convergent extension is a complex morphogenetic process during which cells elongate, move mediolaterally, and intercalate between neighboring cells, leading to convergence toward the mediolateral axis and extension along the anteroposterior axis. Necessary for nuclear localization of REST. May serve as nuclear receptor. {ECO:0000269|PubMed:21901791}.;
Disease: DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. {ECO:0000269|PubMed:21901791}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;Asymmetric localization of PCP proteins;PCP/CE pathway;Beta-catenin independent WNT signaling (Consensus)

Recessive Scores

pRec: 0.146

Intolerance Scores

loftool: 0.0772
rvis_EVS: -0.29
rvis_percentile_EVS: 33.47

Haploinsufficiency Scores

pHI: 0.822
hipred: Y
hipred_score: 0.786
ghis: 0.522

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.632

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Prickle1
Phenotype: vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype;

Zebrafish Information Network

Gene name: prickle1a
Affected structure: hepatocyte
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: neural tube closure;protein import into nucleus;positive regulation of protein ubiquitination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;aorta development;negative regulation of transcription, DNA-templated;Wnt signaling pathway, planar cell polarity pathway;coronary vasculature development;negative regulation of canonical Wnt signaling pathway;negative regulation of cardiac muscle cell myoblast differentiation
Cellular component: nucleus;cytosol;nuclear membrane
Molecular function: protein binding;zinc ion binding