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PLEK2

gene
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Summary

PLEK2 (pleckstrin 2, HGNC:19238) is a protein-coding gene on chromosome 14q23.3-q24.1, encoding Pleckstrin-2 (Q9NYT0). May help orchestrate cytoskeletal arrangement.

The protein encoded by this gene associates with membrane-bound phosphatidylinositols generated by phosphatidylinositol 3-kinase. The encoded protein then interacts with the actin cytoskeleton to induce cell spreading. In conjunction with complement component 1, q subcomponent, B chain (C1QB), this gene shows an increase in expression in melanoma cells and may serve as an accurate biomarker for the disease.

Source: NCBI Gene 26499 — RefSeq curated summary.

At a glance

  • GWAS associations: 8
  • Clinical variants (ClinVar): 2 total
  • MANE Select transcript: NM_016445

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:19238
Approved symbolPLEK2
Namepleckstrin 2
Location14q23.3-q24.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000100558
Ensembl biotypeprotein_coding
OMIM608007
Entrez26499

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000216446, ENST00000553387, ENST00000554395, ENST00000555803, ENST00000556532, ENST00000557388, ENST00000858707

RefSeq mRNA: 1 — MANE Select: NM_016445 NM_016445

CCDS: CCDS9782

Canonical transcript exons

ENST00000216446 — 9 exons

ExonStartEnd
ENSE000006586006738822467388302
ENSE000006586076739540267395583
ENSE000008077696739766267397826
ENSE000024385476738698467387456
ENSE000025151376741201867412165
ENSE000034689596739066367390746
ENSE000035149146739266267392849
ENSE000035923676739232667392427
ENSE000036634526739315067393241

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 98.23.

FANTOM5 (CAGE): breadth broad, TPM avg 5.6541 / max 202.1922, expressed in 910 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
1437345.2130890
1437350.244490
1437330.124461
1437360.064027
1437320.00832

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
oocyteCL:000002398.23gold quality
secondary oocyteCL:000065597.54gold quality
mucosa of transverse colonUBERON:000499194.68gold quality
right adrenal gland cortexUBERON:003582792.38gold quality
right adrenal glandUBERON:000123391.92gold quality
gingival epitheliumUBERON:000194991.76gold quality
left adrenal glandUBERON:000123491.27gold quality
adrenal tissueUBERON:001830391.25gold quality
cervix squamous epitheliumUBERON:000692291.00silver quality
left adrenal gland cortexUBERON:003582591.00gold quality
corpus epididymisUBERON:000435990.95gold quality
rectumUBERON:000105290.87gold quality
adrenal cortexUBERON:000123590.44gold quality
gingivaUBERON:000182889.94gold quality
adrenal glandUBERON:000236989.78gold quality
jejunal mucosaUBERON:000039989.11gold quality
right lobe of thyroid glandUBERON:000111989.09gold quality
duodenumUBERON:000211488.79gold quality
left lobe of thyroid glandUBERON:000112088.75gold quality
epithelial cell of pancreasCL:000008388.68gold quality
colonic mucosaUBERON:000031788.54gold quality
ileal mucosaUBERON:000033188.36gold quality
pancreatic ductal cellCL:000207988.35silver quality
thyroid glandUBERON:000204688.34gold quality
right lobe of liverUBERON:000111488.01gold quality
squamous epitheliumUBERON:000691487.96gold quality
mucosa of sigmoid colonUBERON:000499387.65gold quality
skin of abdomenUBERON:000141686.88gold quality
lower esophagus mucosaUBERON:003583486.71gold quality
skin of legUBERON:000151186.22gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes8.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

34 targeting PLEK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4533100.0069.482758
HSA-MIR-1252-5P100.0069.802774
HSA-MIR-3925-3P100.0069.951237
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-6780B-5P99.9669.602562
HSA-MIR-4725-3P99.9669.532520
HSA-MIR-211099.9666.681930
HSA-MIR-651-3P99.9473.485177
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-427199.8868.322244
HSA-MIR-477999.8666.501583
HSA-MIR-132399.8369.892471
HSA-MIR-548O-3P99.7469.302228
HSA-MIR-1287-3P99.6366.93492
HSA-MIR-9851-3P99.6369.681110
HSA-MIR-4687-3P99.4866.41968
HSA-MIR-766-3P99.4765.241811
HSA-MIR-889-5P99.4168.751025
HSA-MIR-519D-5P99.4169.302057
HSA-MIR-452-3P99.0166.251241
HSA-MIR-873-5P98.8466.901348
HSA-MIR-427298.7668.741810
HSA-MIR-5197-3P98.7167.051905
HSA-MIR-4700-5P98.6367.431915
HSA-MIR-806098.6166.931187
HSA-MIR-508798.0169.09965
HSA-MIR-808997.7466.211698

Literature-anchored findings (GeneRIF, showing 18)

  • Pleckstrin 2 was cloned; its mRNA is widely expressed in a variety of cell lines. (PMID:15865208)
  • pleckstrin-2 uses its modular domains to bind to membrane-associated phosphatidylinositols generated by PI3K, whereby it coordinates with the actin cytoskeleton in lymphocyte spreading and immune synapse formation. (PMID:17008542)
  • These results suggest that PLEK2 is involved in actin rearrangement in a PI 3-kinase dependent manner. (PMID:17658464)
  • expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(-) subsets illustrates the importance of analyzing whole blood cells for biomarker studies (PMID:21698244)
  • On the basis of these collective data, we propose that PLEK2 promotes the invasion and metastasis of GBC by EGFR/CCL2 pathway and PLEK2 can serve as a potential therapeutic target for GBC treatment. (PMID:31182136)
  • High PLEK2 expression is associated with migration and invasion in non-small cell lung cancer. (PMID:31498891)
  • PLEK2 Gene Upregulation Might Independently Predict Shorter Progression-Free Survival in Lung Adenocarcinoma. (PMID:33084541)
  • Expression and prognostic potential of PLEK2 in head and neck squamous cell carcinoma based on bioinformatics analysis. (PMID:34331382)
  • TGF-beta-induced PLEK2 promotes metastasis and chemoresistance in oesophageal squamous cell carcinoma by regulating LCN2. (PMID:34601488)
  • Pleckstrin 2 is a potential drug target for colorectal carcinoma with activation of APC/betacatenin. (PMID:34676872)
  • PLEK2 promotes the proliferation and migration of non-small cell lung cancer cells in a BRD4-dependent manner. (PMID:35122599)
  • The correlation between miR -34a-3p, miR -31, PLEK2 and the occurrence, development and prognosis of colorectal cancer. (PMID:35809313)
  • PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop. (PMID:36002342)
  • Pleckstrin-2-promoted PPM1B degradation plays an important role in transforming growth factor-beta-induced breast cancer cell invasion and metastasis. (PMID:36928924)
  • Pleckstrin-2 promotes tumour immune escape from NK cells by activating the MT1-MMP-MICA signalling axis in gastric cancer. (PMID:37591356)
  • PLEK2 mediates metastasis and invasion via alpha5-nAChR activation in nicotine-induced lung adenocarcinoma. (PMID:37921560)
  • PLEK2 activates the PI3K/AKT signaling pathway to drive lung adenocarcinoma progression by upregulating SPC25. (PMID:38894536)
  • Pleckstrin-2 Mediates the Activation of AKT in Prostate Cancer and Is Repressed by Androgen Receptor. (PMID:39069167)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_rerioplek2ENSDARG00000012789
mus_musculusPlek2ENSMUSG00000021118
rattus_norvegicusPlek2ENSRNOG00000010098

Paralogs (1): PLEK (ENSG00000115956)

Protein

Protein identifiers

Pleckstrin-2 — Q9NYT0 (reviewed: Q9NYT0)

All UniProt accessions (5): Q9NYT0, G3V337, H0YIZ5, H0YJ64, H0YJD0

UniProt curated annotations — full annotation on UniProt →

Function. May help orchestrate cytoskeletal arrangement. Contribute to lamellipodia formation.

Subcellular location. Cell projection. Lamellipodium membrane. Cytoplasm. Cytoskeleton.

RefSeq proteins (1): NP_057529* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000591DEP_domDomain
IPR001849PH_domainDomain
IPR011993PH-like_dom_sfHomologous_superfamily
IPR036388WH-like_DNA-bd_sfHomologous_superfamily
IPR036390WH_DNA-bd_sfHomologous_superfamily
IPR037369PLEK2_DEPDomain
IPR037370PleckstrinFamily

Pfam: PF00169, PF00610

UniProt features (16 total): strand 8, domain 3, modified residue 2, chain 1, helix 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
1X1GSOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9NYT0-F185.980.55

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 (2): 1, 120

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, AMIT_EGF_RESPONSE_480_MCF10A, MARTINEZ_RB1_TARGETS_UP, IRF7_01, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, chr14q24, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (4): actin cytoskeleton organization (GO:0030036), intracellular signal transduction (GO:0035556), positive regulation of plasma membrane bounded cell projection assembly (GO:0120034), positive regulation of cell projection organization (GO:0031346)

GO Molecular Function (3): phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025)

GO Cellular Component (6): cytoskeleton (GO:0005856), plasma membrane (GO:0005886), lamellipodium membrane (GO:0031258), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
intracellular anatomical structure2
phosphatidylinositol phosphate binding2
phosphatidylinositol bisphosphate binding2
cytoskeleton organization1
actin filament-based process1
signal transduction1
positive regulation of cell projection organization1
positive regulation of cellular component biogenesis1
plasma membrane bounded cell projection assembly1
regulation of plasma membrane bounded cell projection assembly1
cell projection organization1
regulation of cell projection organization1
positive regulation of cellular component organization1
intracellular membraneless organelle1
membrane1
cell periphery1
lamellipodium1
cell projection membrane1
leading edge membrane1

Protein interactions and networks

STRING

3274 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PLEK2MCF2P10911969
PLEK2CYTH1Q15438913
PLEK2OSBPP22059910
PLEK2PLCD1P51178902
PLEK2AKT1P31749871
PLEK2SRCP12931868
PLEK2BTKQ06187868
PLEK2RABIFP47224847
PLEK2CDC42P21181843
PLEK2CYTH3O43739821
PLEK2RHOAP06749821
PLEK2ANK1P16157806
PLEK2ANK3Q12955803
PLEK2ANK2Q01484801
PLEK2RASA1P20936800

IntAct

7 interactions, top by confidence:

ABTypeScore
ZNRD2MYO9Apsi-mi:“MI:0914”(association)0.530
AGPSpsi-mi:“MI:0914”(association)0.350
PLEKHG3psi-mi:“MI:0914”(association)0.350
HLA-Cpsi-mi:“MI:0914”(association)0.350
FTLpsi-mi:“MI:0914”(association)0.350
MYO1Cpsi-mi:“MI:0914”(association)0.350

BioGRID (25): PLEK2 (Synthetic Growth Defect), PLEK2 (Affinity Capture-MS), PLEK2 (Proximity Label-MS), PLEK2 (Positive Genetic), PLEK2 (Affinity Capture-MS), EGFR (Affinity Capture-Western), PLEK2 (Affinity Capture-Western), PLEK2 (Affinity Capture-MS), PLEK2 (Co-fractionation), PLEK2 (Co-fractionation), PLEK2 (Affinity Capture-Western), MYC (Affinity Capture-Western), INPPL1 (Affinity Capture-Western), PLEK2 (Affinity Capture-Western), INPPL1 (Reconstituted Complex)

ESM2 similar proteins: O00170, O08915, O75689, O97627, O97628, P08487, P08567, P10686, P16885, P19174, P21146, P24135, P25098, P26817, P26818, P26819, P34512, P35626, P41229, P49619, P49620, P70392, Q09639, Q22070, Q24145, Q38JA7, Q3UYH7, Q4KM33, Q4PMC9, Q5F3R2, Q5FWY5, Q62077, Q64682, Q6IQX0, Q6Q308, Q7YRC1, Q8CIG3, Q8CIH5, Q8NB78, Q8R2V5

Diamond homologs: A0A0G2JUG7, A2A5R2, A5PKW4, A6H7I5, B6RSP1, D3ZL52, D4A631, E1JIT7, F1MUS9, F4IXW2, F4JN05, F4JSZ5, F4K2K3, G3X9K3, G5EET6, G5EGS5, O08967, O13817, O43739, O46382, P08567, P11075, P31749, P31751, P34512, P39052, P39054, P39993, P47102, P47196, P50570, P54644, P60669, P63034, P63035, P97694, P97696, Q00IB7, Q01314, Q10491

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance1
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1483 predictions. Top by Δscore:

VariantEffectΔscore
14:67387454:CCC:Cacceptor_gain1.0000
14:67387455:CC:Cacceptor_gain1.0000
14:67387455:CCC:Cacceptor_gain1.0000
14:67387456:CC:Cacceptor_gain1.0000
14:67387457:C:CCacceptor_gain1.0000
14:67387457:C:CGacceptor_loss1.0000
14:67387458:T:Cacceptor_loss1.0000
14:67390661:A:ACdonor_gain1.0000
14:67390662:C:CCdonor_gain1.0000
14:67392660:A:ACdonor_gain1.0000
14:67392661:C:CCdonor_gain1.0000
14:67392661:CAAA:Cdonor_gain1.0000
14:67392661:CAAAA:Cdonor_gain1.0000
14:67393176:C:Adonor_gain1.0000
14:67393237:TGCGA:Tacceptor_gain1.0000
14:67393239:CGA:Cacceptor_gain1.0000
14:67393240:GA:Gacceptor_gain1.0000
14:67393242:C:CCacceptor_gain1.0000
14:67393245:CA:Cacceptor_gain1.0000
14:67393246:A:Cacceptor_gain1.0000
14:67395400:A:ACdonor_gain1.0000
14:67395400:ACTG:Adonor_gain1.0000
14:67395401:C:CTdonor_gain1.0000
14:67395401:CTG:Cdonor_gain1.0000
14:67395401:CTGC:Cdonor_gain1.0000
14:67395401:CTGCA:Cdonor_gain1.0000
14:67395579:AGGAG:Aacceptor_gain1.0000
14:67395580:GGAG:Gacceptor_gain1.0000
14:67395581:GAG:Gacceptor_gain1.0000
14:67395582:AG:Aacceptor_gain1.0000

AlphaMissense

2311 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
14:67387358:A:GW345R1.000
14:67387358:A:TW345R1.000
14:67390728:A:GW264R1.000
14:67390728:A:TW264R1.000
14:67392329:C:AK256N1.000
14:67392329:C:GK256N1.000
14:67387356:C:AW345C0.999
14:67387356:C:GW345C0.999
14:67387426:A:GF322S0.999
14:67390726:C:AW264C0.999
14:67390726:C:GW264C0.999
14:67395506:C:AW95C0.999
14:67395506:C:GW95C0.999
14:67395508:A:GW95R0.999
14:67395508:A:TW95R0.999
14:67395516:C:GR92P0.999
14:67397806:C:AW21C0.999
14:67397806:C:GW21C0.999
14:67397808:A:GW21R0.999
14:67397808:A:TW21R0.999
14:67412021:C:AK13N0.999
14:67412021:C:GK13N0.999
14:67387357:C:GW345S0.998
14:67387366:C:GR342P0.998
14:67390685:A:GL278P0.998
14:67390706:A:GL271P0.998
14:67390712:A:GF269S0.998
14:67390718:C:GR267P0.998
14:67390719:G:TR267S0.998
14:67390727:C:GW264S0.998

dbSNP variants (sampled 300 via entrez): RS1000170281 (14:67409110 A>T), RS1000221076 (14:67408615 G>A), RS1000311255 (14:67386532 T>A), RS1000371365 (14:67396234 G>A), RS1000420788 (14:67396020 T>C), RS1000555041 (14:67410212 T>C,G), RS1000695231 (14:67401374 T>C), RS1000705950 (14:67397472 G>A), RS1000834419 (14:67392848 G>A,C), RS1000871734 (14:67391076 C>T), RS1000927481 (14:67391724 C>G,T), RS1001045363 (14:67396806 T>C), RS1001138903 (14:67403177 G>A,T), RS1001174314 (14:67407537 C>T), RS1001210407 (14:67409955 T>C)

Disease associations

OMIM: gene MIM:608007 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

StudyTraitp-value
GCST004024_1Depressive symptom measurement or major depressive disorder4.000000e-06
GCST004611_198High light scatter reticulocyte count4.000000e-12
GCST004612_132High light scatter reticulocyte percentage of red cells5.000000e-12
GCST004628_57Immature fraction of reticulocytes7.000000e-20
GCST007256_1Broad depression or major depressive disorder (recurrent)4.000000e-09
GCST90002385_29High light scatter reticulocyte count2.000000e-21
GCST90002386_173High light scatter reticulocyte percentage of red cells1.000000e-21
GCST90002387_146Immature fraction of reticulocytes9.000000e-45

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0007006depressive symptom measurement
EFO:0007986reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
sodium arseniteincreases abundance, increases expression, decreases expression3
Benzo(a)pyreneaffects methylation, decreases methylation, increases expression3
potassium chromate(VI)affects cotreatment, decreases expression2
bisphenol Saffects cotreatment, increases methylation, increases expression2
Estradiolaffects cotreatment, increases expression, decreases expression2
Aflatoxin B1increases expression, increases methylation2
sotorasibdecreases expression, affects cotreatment1
propionaldehydeincreases expression1
bisphenol Aincreases methylation, affects cotreatment1
ethyl-p-hydroxybenzoateincreases expression1
arseniteincreases methylation1
butyraldehydeincreases expression1
cupric chlorideincreases expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression1
epigallocatechin gallateaffects cotreatment, decreases expression1
pentanalincreases expression1
chromium hexavalent iondecreases expression1
chloropicrindecreases expression1
erucylphospho-N,N,N-trimethylpropylammoniumincreases expression1
ICG 001decreases expression1
jinfukangdecreases expression, affects cotreatment1
trametinibaffects cotreatment, decreases expression1
NVP-BKM120affects cotreatment, decreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Temozolomidedecreases expression1
Arsenic Trioxidedecreases response to substance1
Fulvestrantaffects cotreatment, increases methylation1
Acetaminophendecreases expression1
Air Pollutantsincreases expression1
Aldehydesincreases expression1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot