PRICKLE4

Summary

PRICKLE4 (prickle planar cell polarity protein 4, HGNC:16805) is a protein-coding gene on chromosome 6p21.1, encoding Prickle-like protein 4 (Q2TBC4).

C6ORF49 is a member of the LIM domain protein family (Teufel et al., 2005 [PubMed 15702247]).

Source: NCBI Gene 29964 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_013397

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16805
Approved symbol	PRICKLE4
Name	prickle planar cell polarity protein 4
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	OEBT, DKFZp761H221
Ensembl gene	ENSG00000278224
Ensembl biotype	protein_coding
OMIM	611389
Entrez	29964

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000359201, ENST00000394259, ENST00000394260, ENST00000458694, ENST00000463606, ENST00000483200, ENST00000938055

RefSeq mRNA: 1 — MANE Select: NM_013397 NM_013397

CCDS: CCDS34449

Canonical transcript exons

ENST00000458694 — 8 exons

Exon	Start	End
ENSE00001429033	41780782	41780826
ENSE00003718908	41785337	41785540
ENSE00003727706	41786128	41786332
ENSE00003738082	41784131	41784238
ENSE00003746692	41784935	41785072
ENSE00003802038	41781350	41781520
ENSE00003805316	41783462	41783605
ENSE00003896303	41786762	41787452

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 85.58.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4232 / max 41.6971, expressed in 634 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67771	1.4100	632
67772	0.0133	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.43	gold quality
right lobe of thyroid gland	UBERON:0001119	82.30	gold quality
thyroid gland	UBERON:0002046	81.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.08	gold quality
spleen	UBERON:0002106	80.71	gold quality
left lobe of thyroid gland	UBERON:0001120	80.67	gold quality
cerebellar hemisphere	UBERON:0002245	80.57	gold quality
apex of heart	UBERON:0002098	80.47	gold quality
cerebellar cortex	UBERON:0002129	80.19	gold quality
right uterine tube	UBERON:0001302	80.18	gold quality
cerebellum	UBERON:0002037	79.91	gold quality
body of uterus	UBERON:0009853	79.24	gold quality
myometrium	UBERON:0001296	79.06	gold quality
ectocervix	UBERON:0012249	78.82	gold quality
esophagus mucosa	UBERON:0002469	78.71	gold quality
pituitary gland	UBERON:0000007	78.62	gold quality
uterine cervix	UBERON:0000002	78.60	gold quality
right lung	UBERON:0002167	78.56	gold quality
endocervix	UBERON:0000458	78.29	gold quality
prostate gland	UBERON:0002367	77.87	gold quality
vagina	UBERON:0000996	77.66	gold quality
fundus of stomach	UBERON:0001160	77.42	gold quality
right ovary	UBERON:0002118	77.11	gold quality
esophagus	UBERON:0001043	77.06	gold quality
adenohypophysis	UBERON:0002196	76.83	gold quality
Ammon’s horn	UBERON:0001954	76.78	gold quality
gall bladder	UBERON:0002110	76.76	gold quality
substantia nigra	UBERON:0002038	76.58	gold quality
left uterine tube	UBERON:0001303	76.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6678	no	2.42
E-ANND-3	no	0.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting PRICKLE4, 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-2110	99.96	66.68	1930
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-4264	96.35	64.76	1480

Literature-anchored findings (GeneRIF, showing 1)

• molecular characterization of OEBT (PMID:15702247)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prickle4	ENSMUSG00000096549
rattus_norvegicus	Prickle4	ENSRNOG00000014180
drosophila_melanogaster	Zasp52	FBGN0265991
caenorhabditis_elegans		WBGENE00001132

Paralogs (7): PDLIM1 (ENSG00000107438), PDLIM2 (ENSG00000120913), LDB3 (ENSG00000122367), PDLIM4 (ENSG00000131435), PDLIM3 (ENSG00000154553), PDLIM5 (ENSG00000163110), PDLIM7 (ENSG00000196923)

Protein

Protein identifiers

Prickle-like protein 4 — Q2TBC4 (reviewed: Q2TBC4)

Alternative names: Overexpressed breast tumor protein

All UniProt accessions (2): Q2TBC4, A0A0U1RQR5

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in a broad range of normal tissues as well as in hepatocellular carcinoma, breast cancer and prostate cancer tissues.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q2TBC4-1	1	yes
Q2TBC4-2	2
Q2TBC4-3	3

RefSeq proteins (1): NP_037529* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR010442	PET_domain	Domain
IPR047120	Pk/Esn/Tes	Family

Pfam: PF00412, PF06297

UniProt features (12 total): domain 3, compositionally biased region 3, splice variant 2, chain 1, sequence variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2TBC4-F1	69.47	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): TGCGCANK_UNKNOWN, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, RYTTCCTG_ETS2_B, GOMF_ACTIN_BINDING, GOCC_CELL_CELL_JUNCTION, ACEVEDO_LIVER_CANCER_UP, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOCC_I_BAND, GOCC_ACTIN_FILAMENT_BUNDLE, GOCC_ACTOMYOSIN, GOCC_ANCHORING_JUNCTION, GOCC_FILAMENTOUS_ACTIN, GOMF_ACTININ_BINDING, GOMF_CYTOSKELETAL_PROTEIN_BINDING, NFAT_Q6

GO Biological Process (3): heart development (GO:0007507), actin cytoskeleton organization (GO:0030036), muscle structure development (GO:0061061)

GO Molecular Function (5): actin binding (GO:0003779), zinc ion binding (GO:0008270), muscle alpha-actinin binding (GO:0051371), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): stress fiber (GO:0001725), nucleus (GO:0005634), adherens junction (GO:0005912), Z disc (GO:0030018), filamentous actin (GO:0031941)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	1
circulatory system development	1
cytoskeleton organization	1
actin filament-based process	1
anatomical structure development	1
cytoskeletal protein binding	1
transition metal ion binding	1
alpha-actinin binding	1
binding	1
cation binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
cell-cell junction	1
I band	1
cellular anatomical structure	1
actin filament	1
protein-containing complex	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRICKLE4	VANGL2	Q9ULK5	960
PRICKLE4	DVL1	O14640	893
PRICKLE4	ANKRD6	Q9Y2G4	844
PRICKLE4	VANGL1	Q8TAA9	838
PRICKLE4	CELSR1	Q9NYQ6	750
PRICKLE4	PTPRU	P78399	696
PRICKLE4	DVL2	O14641	635
PRICKLE4	INVS	Q9Y283	630
PRICKLE4	ARHGAP21	Q5T5U3	628
PRICKLE4	FZD6	O60353	625
PRICKLE4	FZD3	Q9NPG1	611
PRICKLE4	CELSR3	Q9NYQ7	605
PRICKLE4	DAAM1	Q9Y4D1	581
PRICKLE4	CDH17	Q12864	571
PRICKLE4	INTU	Q9ULD6	570

IntAct

3 interactions, top by confidence:

A	B	Type	Score
METAP1D	PRICKLE4	psi-mi:“MI:0915”(physical association)	0.500
PRICKLE4	USO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): PRICKLE4 (Protein-RNA), PRICKLE4 (Two-hybrid), PRICKLE4 (Two-hybrid), PRICKLE4 (Two-hybrid), GNE (Two-hybrid), AGXT (Two-hybrid), ZNF417 (Two-hybrid), PLEKHN1 (Two-hybrid), ZNF587 (Two-hybrid), PRICKLE4 (Two-hybrid), PRICKLE4 (Two-hybrid), PRICKLE4 (Two-hybrid), PRICKLE4 (Two-hybrid), PRICKLE4 (Two-hybrid), PRICKLE4 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1575 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41780825:GG:G	donor_gain	1.0000
6:41780826:GG:G	donor_gain	1.0000
6:41783791:A:AG	donor_gain	1.0000
6:41784230:GACAT:G	donor_gain	1.0000
6:41784236:GAT:G	donor_gain	1.0000
6:41784237:ATG:A	donor_loss	1.0000
6:41784238:TG:T	donor_loss	1.0000
6:41784239:G:GG	donor_gain	1.0000
6:41785007:G:GT	donor_gain	1.0000
6:41785069:GAAG:G	donor_gain	1.0000
6:41785070:AAGG:A	donor_loss	1.0000
6:41785072:GGTA:G	donor_loss	1.0000
6:41785073:G:GA	donor_loss	1.0000
6:41785471:T:TA	acceptor_gain	1.0000
6:41785538:CAGG:C	donor_loss	1.0000
6:41785539:AGGT:A	donor_loss	1.0000
6:41785540:GG:G	donor_loss	1.0000
6:41785541:G:A	donor_loss	1.0000
6:41785542:T:G	donor_loss	1.0000
6:41786123:CCCAG:C	acceptor_loss	1.0000
6:41786124:CCAG:C	acceptor_loss	1.0000
6:41786125:CAGCT:C	acceptor_loss	1.0000
6:41786126:A:AG	acceptor_gain	1.0000
6:41786126:AGCT:A	acceptor_gain	1.0000
6:41786127:G:GG	acceptor_gain	1.0000
6:41786127:G:GT	acceptor_loss	1.0000
6:41786127:GC:G	acceptor_gain	1.0000
6:41786127:GCT:G	acceptor_gain	1.0000
6:41786127:GCTG:G	acceptor_gain	1.0000
6:41780972:G:T	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000339060 (6:41781958 A>G), RS1000565706 (6:41787689 C>T), RS1001295107 (6:41781253 G>A), RS1002066436 (6:41786702 T>C), RS1002401169 (6:41787387 A>C), RS1002741924 (6:41784087 G>C), RS1004079126 (6:41783389 A>G), RS1004418361 (6:41782661 G>A), RS1004534021 (6:41782967 T>G), RS1005755610 (6:41785652 G>T), RS1005814974 (6:41780725 G>A), RS1006088554 (6:41786312 T>C), RS1006255653 (6:41780176 G>A), RS1006663778 (6:41784833 C>T), RS1006720166 (6:41779563 G>A)

Disease associations

OMIM: gene MIM:611389 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012227_976	Hip circumference adjusted for BMI	5.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroxyhydroquinone	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tunicamycin	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	increases expression	1
Magnetite Nanoparticles	decreases methylation	1

Clinical trials (associated diseases)

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