PRICKLE1

Summary

PRICKLE1 (prickle planar cell polarity protein 1, HGNC:17019) is a protein-coding gene on chromosome 12q12, encoding Prickle-like protein 1 (Q96MT3). Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.

This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway. The encoded protein localizes to the nuclear membrane and has been implicated in the nuclear trafficking of the transcription repressors REST/NRSF and REST4. Mutations in this gene have been linked to progressive myoclonus epilepsy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3.

Source: NCBI Gene 144165 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy, progressive myoclonic, 1B (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 519 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_153026

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17019
Approved symbol	PRICKLE1
Name	prickle planar cell polarity protein 1
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31937, EPM1B, RILP
Ensembl gene	ENSG00000139174
Ensembl biotype	protein_coding
OMIM	608500
Entrez	144165

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 36 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000345127, ENST00000445766, ENST00000455697, ENST00000547113, ENST00000548696, ENST00000551050, ENST00000552108, ENST00000552200, ENST00000552240, ENST00000639414, ENST00000639566, ENST00000639588, ENST00000639589, ENST00000639958, ENST00000640055, ENST00000640132, ENST00000640361, ENST00000640646, ENST00000640801, ENST00000640840, ENST00000640946, ENST00000899955, ENST00000899956, ENST00000899957, ENST00000899958, ENST00000899959, ENST00000899960, ENST00000899961, ENST00000899962, ENST00000899963, ENST00000914366, ENST00000914367, ENST00000914368, ENST00000914369, ENST00000914370, ENST00000914371, ENST00000914372, ENST00000945641, ENST00000945642, ENST00000945643, ENST00000945644, ENST00000945645

RefSeq mRNA: 4 — MANE Select: NM_153026 NM_001144881, NM_001144882, NM_001144883, NM_153026

CCDS: CCDS8742

Canonical transcript exons

ENST00000345127 — 8 exons

Exon	Start	End
ENSE00000936845	42466194	42466380
ENSE00001098593	42468626	42468829
ENSE00001098595	42470246	42470359
ENSE00001098601	42469450	42469587
ENSE00001098602	42464395	42465258
ENSE00001216305	42472385	42472564
ENSE00002325576	42456757	42460665
ENSE00003801912	42589465	42589746

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2923 / max 244.6511, expressed in 1338 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130494	6.6257	1150
130495	0.6269	280
130492	0.6055	204
130496	0.5307	284
130489	0.4785	275
130490	0.4665	273
130493	0.3569	204
130491	0.3428	114
130488	0.1405	47
206674	0.0609	13

Top tissues by expression

249 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.86	gold quality
tendon of biceps brachii	UBERON:0008188	96.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.20	gold quality
oviduct epithelium	UBERON:0004804	95.54	gold quality
dorsal root ganglion	UBERON:0000044	95.49	gold quality
endothelial cell	CL:0000115	94.96	gold quality
trigeminal ganglion	UBERON:0001675	93.73	gold quality
left ventricle myocardium	UBERON:0006566	93.38	gold quality
parietal pleura	UBERON:0002400	93.27	gold quality
medial globus pallidus	UBERON:0002477	92.98	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.82	gold quality
pericardium	UBERON:0002407	92.78	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.69	gold quality
sural nerve	UBERON:0015488	92.58	gold quality
tibia	UBERON:0000979	92.06	gold quality
nipple	UBERON:0002030	91.09	gold quality
middle temporal gyrus	UBERON:0002771	90.28	gold quality
myocardium	UBERON:0002349	90.25	gold quality
parietal lobe	UBERON:0001872	90.01	gold quality
visceral pleura	UBERON:0002401	89.94	gold quality
postcentral gyrus	UBERON:0002581	89.61	gold quality
superior frontal gyrus	UBERON:0002661	89.36	gold quality
globus pallidus	UBERON:0001875	89.07	gold quality
entorhinal cortex	UBERON:0002728	88.84	gold quality
occipital lobe	UBERON:0002021	88.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.34	gold quality
primary visual cortex	UBERON:0002436	87.46	gold quality
cortical plate	UBERON:0005343	87.45	gold quality
urethra	UBERON:0000057	87.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	57.48
E-MTAB-9067	yes	11.55
E-ANND-3	yes	6.55
E-MTAB-6142	no	109.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting PRICKLE1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 18)

• PRICKLE1 and PRICKLE2 mRNAs were expressed together in brain, eye and testis. (PMID:12525887)
• A physical and functional interaction between Prickle and Strabismus was found in Drosophila and Xenopus, but is likely conserved in human, too. (PMID:12941693)
• appears to serve as a nuclear receptor for REST/NRSF, REST4, and possibly other transcription factors (PMID:14645515)
• NRSF/REST functions as a repressor of TH transcription in NSCs via a mechanism dependent on the TH NRSE/RE1 sites. (PMID:16764822)
• Prickle-1 is a negative regulator of the Wnt/beta-catenin signaling pathway and is a putative tumor suppressor in human hepatocellular carcinoma (PMID:17030191)
• A homozygous mutation in PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. (PMID:18976727)
• PRICKLE1 mutations are not a frequent cause of progressive myoclous epilepsies in Southern Italy. (PMID:20842693)
• Mutations in prickle1 causes seizures. (PMID:21276947)
• study demonstrates that PRICKLE1 could act as a predisposing factor to human neural tube defects (PMID:21901791)
• MINK1 interacts with and phosphorylates PRICKLE1 and PRICKLE2. (PMID:22037766)
• these findings suggest PRICKLE1 mutations contribute to ASD by disrupting the interaction with SYN1 and regulation of synaptic vesicles. (PMID:24312498)
• Our experimental data demonstrate that high expression of Prickle1 and Vangl2 reduce the growth of neuroblastoma cells and indicate different roles of PCP proteins in tumorigenic cells compared to normal cells. (PMID:27036398)
• upregulation of PRICKLE1 in basal breast cancers, a subtype characterized by high metastatic potential, is associated with poor metastasis-free survival. (PMID:27184734)
• Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5beta, and to promote microtubule targeting of focal adhesions. (PMID:27378169)
• This clinical report highlights the fact that in the context of an epileptic encephalopathy with developmental arrest, early onset severe PME-ataxia syndrome can be a PRICKLE1-associated phenotype (PMID:30345727)
• showed that the patient’s father (p.Asp760del) and mother (p.Asp201Asn) each had a mutation in prickle1 (PMID:30564977)
• Authors used a proteomic approach to identify protein complexes associated with PRICKLE1. The mRNA expression levels of the corresponding genes were assessed in 8982 patients with invasive primary breast cancer. AUthors then characterised the molecular interaction between PRICKLE1 and the guanine nucleotide exchange factor ECT2. (PMID:30971775)
• PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia. (PMID:34001134)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	prickle1a	ENSDARG00000040649
danio_rerio	prickle1b	ENSDARG00000045694
mus_musculus	Prickle1	ENSMUSG00000036158
rattus_norvegicus	Prickle1	ENSRNOG00000022772
drosophila_melanogaster	Tes	FBGN0034223
caenorhabditis_elegans		WBGENE00004112
caenorhabditis_elegans		WBGENE00015217

Paralogs (3): LMCD1 (ENSG00000071282), TES (ENSG00000135269), LIMD2 (ENSG00000136490)

Protein

Protein identifiers

Prickle-like protein 1 — Q96MT3 (reviewed: Q96MT3)

Alternative names: REST/NRSF-interacting LIM domain protein 1

All UniProt accessions (5): Q96MT3, A0A1W2PPC7, F8VUG8, F8W1J1, F8W1Q8

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with REST.

Subcellular location. Nucleus membrane. Cytoplasm. Cytosol.

Tissue specificity. Expressed at highest levels in placenta and at lower levels in lung, liver, kidney and pancreas. Expressed in thalamus, hippocampus, cerebral cortex, and cerebellum (in neurons rather than glia).

Disease relevance. Epilepsy, progressive myoclonic 1B (EPM1B) [MIM:612437] A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM1B is an autosomal recessive form characterized by myoclonus that progressed in severity over time, tonic-clonic seizures and ataxia. The disease is caused by variants affecting the gene represented in this entry. 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. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the prickle / espinas / testin family.

RefSeq proteins (4): NP_001138353, NP_001138354, NP_001138355, NP_694571* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR010442	PET_domain	Domain
IPR033723	PET_prickle	Domain
IPR033726	LIM2_prickle	Domain
IPR033727	LIM3_prickle	Domain
IPR047120	Pk/Esn/Tes	Family

Pfam: PF00412, PF06297

UniProt features (32 total): sequence variant 13, modified residue 5, domain 4, region of interest 3, compositionally biased region 2, chain 1, propeptide 1, lipid moiety-binding region 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MT3-F1	55.55	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 315, 591, 594, 683, 828, 828

Mutagenesis-validated functional residues (1):

Position	Phenotype
828–831	abolishes localization to the nuclear membrane.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-4608870	Asymmetric localization of PCP proteins

MSigDB gene sets: 566 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_DENDRITE_DEVELOPMENT, GOBP_CHROMOSOME_ORGANIZATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_LYSOSOMAL_TRANSPORT, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_ENDOSOME_ORGANIZATION, GOBP_CORONARY_VASCULATURE_DEVELOPMENT

GO Biological Process (63): neural tube closure (GO:0001843), tissue homeostasis (GO:0001894), outflow tract morphogenesis (GO:0003151), protein import into nucleus (GO:0006606), apoptotic process (GO:0006915), epidermal growth factor receptor signaling pathway (GO:0007173), axonogenesis (GO:0007409), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), vesicle-mediated transport (GO:0016192), dendrite development (GO:0016358), bone mineralization (GO:0030282), cytoskeleton-dependent intracellular transport (GO:0030705), positive regulation of protein ubiquitination (GO:0031398), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), multicellular organism growth (GO:0035264), embryonic nail plate morphogenesis (GO:0035880), aorta development (GO:0035904), post-anal tail morphogenesis (GO:0036342), negative regulation of DNA-templated transcription (GO:0045892), response to electrical stimulus (GO:0051602), cardiac muscle cell development (GO:0055013), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), cilium assembly (GO:0060271), face morphogenesis (GO:0060325), mesenchyme development (GO:0060485), coronary vasculature development (GO:0060976), eyelid development in camera-type eye (GO:0061029), establishment of bipolar cell polarity involved in cell morphogenesis (GO:0061159), cornea development in camera-type eye (GO:0061303), renal tubule development (GO:0061326), polarized secretion of basement membrane proteins in epithelium (GO:0061865), tear secretion (GO:0070075), basement membrane organization (GO:0071711), extracellular matrix assembly (GO:0085029), primitive streak formation (GO:0090009), negative regulation of canonical Wnt signaling pathway (GO:0090090), mitotic spindle assembly (GO:0090307), cell-cell adhesion (GO:0098609), regulation of postsynaptic density assembly (GO:0099151)

GO Molecular Function (4): zinc ion binding (GO:0008270), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): proteasome complex (GO:0000502), nucleus (GO:0005634), cytosol (GO:0005829), postsynaptic density (GO:0014069), cell trailing edge (GO:0031254), nuclear membrane (GO:0031965), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PCP/CE pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
anatomical structure morphogenesis	2
binding	2
primary neural tube formation	1
tube closure	1
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
heart morphogenesis	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
ERBB signaling pathway	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
response to chemical	1
macromolecule biosynthetic process	1
transport	1
cellular process	1
neuron projection development	1
anatomical structure development	1
ossification	1
biomineral tissue development	1
intracellular transport	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
multicellular organismal process	1
developmental growth	1
nail development	1
embryonic digit morphogenesis	1
embryonic morphogenesis	1

Protein interactions and networks

STRING

1410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRICKLE1	VANGL2	Q9ULK5	980
PRICKLE1	DVL1	O14640	947
PRICKLE1	VANGL1	Q8TAA9	906
PRICKLE1	ANKRD6	Q9Y2G4	831
PRICKLE1	KCTD7	Q96MP8	812
PRICKLE1	CSTB	P04080	808
PRICKLE1	CELSR1	Q9NYQ6	763
PRICKLE1	ARHGAP21	Q5T5U3	757
PRICKLE1	PHLDB2	Q86SQ0	739
PRICKLE1	DAAM1	Q9Y4D1	727
PRICKLE1	FZD3	Q9NPG1	704
PRICKLE1	NHLRC1	Q6VVB1	680
PRICKLE1	FZD7	O75084	663
PRICKLE1	DVL2	O14641	661
PRICKLE1	FZD6	O60353	648

IntAct

39 interactions, top by confidence:

A	B	Type	Score
PRICKLE1	PRPF31	psi-mi:“MI:0915”(physical association)	0.720
PRPF31	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.720
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
PRICKLE1	Rest	psi-mi:“MI:0915”(physical association)	0.590
UTP14C	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.560
PRICKLE1	UTP14C	psi-mi:“MI:0915”(physical association)	0.560
JRK	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.560
BYSL	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.560
PRICKLE1	KIF9	psi-mi:“MI:0915”(physical association)	0.560
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
PRICKLE1	Smurf2	psi-mi:“MI:0915”(physical association)	0.400
DVL2	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.400
Pard6a	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.400
PRICKLE1	DVL3	psi-mi:“MI:0915”(physical association)	0.400
DVL3	PRICKLE1	psi-mi:“MI:0915”(physical association)	0.400
PRICKLE1	UTP14C	psi-mi:“MI:0915”(physical association)	0.370
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
KCNE3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ADCYAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
ARHGEF10L	SOWAHC	psi-mi:“MI:0914”(association)	0.350
SLC43A2	PIK3R2	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): PRICKLE1 (Two-hybrid), PRICKLE1 (Two-hybrid), PRICKLE1 (Affinity Capture-MS), Tanc2 (Affinity Capture-MS), Tanc1 (Affinity Capture-MS), Usp9x (Affinity Capture-MS), Bcr (Affinity Capture-MS), Mycbp2 (Affinity Capture-MS), Rpl23 (Affinity Capture-MS), Cad (Affinity Capture-MS), Rpl4 (Affinity Capture-MS), Rps26 (Affinity Capture-MS), Tubb4b (Affinity Capture-MS), Tubb5 (Affinity Capture-MS), Tanc2 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8H8C0, A0A1L8HFX9, A2CEX1, A2RUV4, A4V8B4, A8XU52, C5DGS4, C5DT56, E7KIY3, E9QDC5, F1QPR4, G5EEK3, H2L045, O60504, P27715, Q02645, Q02831, Q11181, Q32NM7, Q3U5C7, Q571K4, Q5T5U3, Q5U303, Q60JJ0, Q6DFG0, Q6DFV3, Q71H61, Q71M21, Q71QF9, Q7Z3G6, Q7ZXH3, Q80Y24, Q86SQ0, Q8BRG8, Q8K1N2, Q8N5C8, Q8NEY8, Q8VEB2, Q96MT3, Q96SK2

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O43294, O43900, P47226, Q00PK1, Q04650, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q174I2, Q17QE2, Q28FG2, Q292U2, Q292U5, Q2IBA3, Q2IBC3, Q2IBH0, Q2LAP6, Q2QL92, Q2QLA1, Q2QLB2, Q2QLC3, Q2QLE3, Q2QLF4, Q2QLG8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MINK1	“up-regulates activity”	PRICKLE1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

519 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	301
Likely benign	165
Benign	27

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
30730	NM_153026.3(PRICKLE1):c.1414T>C (p.Tyr472His)	Pathogenic
929390	GRCh37/hg19 12q12(chr12:42871679-42898233)x1	Likely pathogenic

SpliceAI

3168 predictions. Top by Δscore:

Variant	Effect	Δscore
12:42465258:CCTG:C	acceptor_loss	1.0000
12:42465259:C:CA	acceptor_loss	1.0000
12:42465260:T:A	acceptor_loss	1.0000
12:42465264:T:TC	acceptor_gain	1.0000
12:42466187:GACTT:G	donor_loss	1.0000
12:42466188:ACTTA:A	donor_loss	1.0000
12:42466189:CTTA:C	donor_loss	1.0000
12:42466190:TTA:T	donor_loss	1.0000
12:42466191:T:TG	donor_loss	1.0000
12:42466192:A:AC	donor_gain	1.0000
12:42466193:C:CT	donor_gain	1.0000
12:42466193:CCAAT:C	donor_gain	1.0000
12:42466376:ATTAT:A	acceptor_gain	1.0000
12:42466377:TTAT:T	acceptor_gain	1.0000
12:42466378:TAT:T	acceptor_gain	1.0000
12:42466379:AT:A	acceptor_gain	1.0000
12:42466381:C:CC	acceptor_gain	1.0000
12:42466382:T:G	acceptor_loss	1.0000
12:42466384:C:CT	acceptor_gain	1.0000
12:42466385:A:T	acceptor_gain	1.0000
12:42466393:A:AC	acceptor_gain	1.0000
12:42466393:A:C	acceptor_gain	1.0000
12:42466395:G:GC	acceptor_gain	1.0000
12:42466402:C:CT	acceptor_gain	1.0000
12:42466402:C:T	acceptor_gain	1.0000
12:42466403:A:T	acceptor_gain	1.0000
12:42468735:G:C	acceptor_gain	1.0000
12:42468825:CCACA:C	acceptor_gain	1.0000
12:42468826:CACAC:C	acceptor_gain	1.0000
12:42468828:CA:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013176 (12:42566493 C>T), RS1000023848 (12:42519845 T>C), RS1000046355 (12:42482531 T>A,C), RS1000051708 (12:42519115 A>G), RS1000105396 (12:42518699 G>A,T), RS1000110957 (12:42491579 A>G), RS1000117863 (12:42481063 TG>T), RS1000137606 (12:42585529 T>C), RS1000145462 (12:42462555 A>T), RS1000197039 (12:42533855 C>A), RS1000220751 (12:42541678 T>A), RS1000235272 (12:42513051 C>T), RS1000262859 (12:42580465 A>G), RS1000268212 (12:42476464 G>A,C), RS1000272175 (12:42480690 T>A,C)

Disease associations

OMIM: gene MIM:608500 | disease phenotypes: MIM:612437, MIM:117100, MIM:617468, MIM:208150

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy, progressive myoclonic, 1B	Strong	Autosomal recessive
Unverricht-Lundborg syndrome	Supportive	Autosomal recessive
epilepsy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Disputed	AD
progressive myoclonus epilepsy	Limited	AR

Mondo (7): epilepsy, progressive myoclonic, 1B (MONDO:0012904), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), intellectual disability (MONDO:0001071), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), Unverricht-Lundborg syndrome (MONDO:0009698), epilepsy (MONDO:0005027)

Orphanet (5): Progressive myoclonic epilepsy type 1 (Orphanet:308), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000726	Dementia
HP:0000992	Cutaneous photosensitivity
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001310	Dysmetria
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0002070	Limb ataxia
HP:0002080	Intention tremor
HP:0002123	Generalized myoclonic seizure
HP:0002392	EEG with polyspike wave complexes
HP:0003390	Sensory axonal neuropathy
HP:0003487	Babinski sign
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0007000	Morning myoclonic jerks
HP:0010819	Atonic seizure

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000675_1	Heart failure	1.000000e-06
GCST001524_36	Visceral adipose tissue/subcutaneous adipose tissue ratio	1.000000e-06
GCST003542_102	Night sleep phenotypes	9.000000e-06
GCST003984_16	Parkinson’s disease	5.000000e-09
GCST005524_7	Autoimmune thyroid diseases (Graves disease or Hashimoto’s thyroiditis)	4.000000e-06
GCST005526_7	Graves’ disease	3.000000e-07
GCST006466_6	Endometrial cancer (Non-endometrioid histology)	3.000000e-07
GCST007552_39	Colorectal cancer	1.000000e-08
GCST007629_3	Impulsivity (non-planning)	4.000000e-07
GCST008062_60	Blood urea nitrogen levels	2.000000e-17
GCST008156_85	Hip circumference adjusted for BMI	6.000000e-06
GCST009184_9	Inferior parietal cortex volume	7.000000e-07
GCST009597_26	Multiple sclerosis	9.000000e-06
GCST009869_61	Colorectal cancer	2.000000e-09
GCST010002_215	Refractive error	3.000000e-11
GCST90000025_1034	Appendicular lean mass	1.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0006946	behavioural disinhibition measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020194	Unverricht-Lundborg Syndrome	C10.228.140.490.375.130.650.900; C10.228.140.490.493.063.650.900; C10.574.500.875; C16.320.400.940
C580388	Prickle1-Related Progressive Myoclonic Epilepsy with Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, decreases expression	3
Tobacco Smoke Pollution	decreases expression	3
bisphenol A	decreases expression	2
sodium arsenite	decreases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases expression, increases abundance	2
entinostat	decreases expression, affects cotreatment	2
Acrolein	affects cotreatment, decreases expression, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cisplatin	decreases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	decreases expression	2
Ozone	affects cotreatment, decreases expression, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
tobacco tar	increases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5R1	SEES3-1V human PRICKLE1, clone1	Embryonic stem cell	Male
CVCL_A5R2	SEES3-1V human PRICKLE1, clone2	Embryonic stem cell	Male
CVCL_A5R3	SEES3-1V human PRICKLE1, clone3	Embryonic stem cell	Male
CVCL_D9PB	Ubigene HEK293 PRICKLE1 KO	Transformed cell line	Female
CVCL_E0LM	Ubigene HeLa PRICKLE1 KO	Cancer cell line	Female
CVCL_E2HQ	HAP1 PRICKLE1 (-) 1	Cancer cell line	Male
CVCL_E2HR	HAP1 PRICKLE1 (-) 2	Cancer cell line	Male
CVCL_E2HS	HAP1 PRICKLE1 (-) 3	Cancer cell line	Male
CVCL_E2HT	HAP1 PRICKLE1 (-) 4	Cancer cell line	Male
CVCL_E2HU	HAP1 PRICKLE1 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

509 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy