PLEK2

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): 1 total
• GTEx eGene: eQTL in 24 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_016445
• Interaction hub: 2,692 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19238
Approved symbol	PLEK2
Name	pleckstrin 2
Location	14q23.3-q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100558
Ensembl biotype	protein_coding
OMIM	608007
Entrez	26499

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000216446

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 2, TSL 5: 3

ENST00000216446, ENST00000553387, ENST00000554395, ENST00000555803, ENST00000556532, ENST00000557388, ENST00000858707, ENST00000998134, ENST00001051484, ENST00001051485, ENST00001119996, ENST00001137480

RefSeq mRNA: 1 — MANE Select: NM_016445 NM_016445

CCDS: CCDS9782

Canonical transcript exons

ENST00000216446 — 9 exons

Exon	Start	End
ENSE00000658600	67388224	67388302
ENSE00000658607	67395402	67395583
ENSE00000807769	67397662	67397826
ENSE00002438547	67386984	67387456
ENSE00002515137	67412018	67412165
ENSE00003468959	67390663	67390746
ENSE00003514914	67392662	67392849
ENSE00003592367	67392326	67392427
ENSE00003663452	67393150	67393241

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.

Highest expression (Bgee): oocyte, secondary oocyte, mucosa of transverse colon, adrenal gland cortex, adrenal gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLEK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	eqtl	6.8e-37	+0.78	14:67397156:G:C
Adipose Visceral Omentum	eqtl	2.9e-31	+0.65	14:67401396:A:G
Heart Atrial Appendage	eqtl	5.3e-21	+0.82	14:67401396:A:G
Colon Transverse	eqtl	1.1e-13	+0.21	14:67418453:T:G
Pancreas	eqtl	4.8e-12	+0.41	14:67412320:A:G
Thyroid	eqtl	4.0e-09	-0.22	14:67266144:G:A
Brain Cerebellar Hemisphere	eqtl	6.4e-09	+1.22	14:67473949:G:C
Brain Cerebellum	eqtl	1.0e-06	+1.25	14:67473949:G:C
Liver	eqtl	1.0e-06	-0.74	14:67246340:A:G
Heart Left Ventricle	eqtl	3.4e-06	+0.50	14:67397156:G:C
Brain Anterior cingulate cortex BA24	eqtl	6.4e-06	+1.17	14:67473949:G:C
Skin Sun Exposed Lower leg	eqtl	2.9e-05	+0.13	14:67418453:T:G
Skin Not Sun Exposed Suprapubic	eqtl	6.6e-05	+0.13	14:67420631:T:C
Spleen	eqtl	5.4e-04	+1.21	14:66877436:G:A
Cells Cultured fibroblasts	eqtl	6.9e-04	-0.18	14:67197769:G:A
Thyroid	sqtl	5.5e-03	-1.10	14:66891512:G:A
Stomach	eqtl	6.3e-03	+0.12	14:67419400:C:A
Breast Mammary Tissue	eqtl	1.0e-02	-0.45	14:67864616:T:C
Artery Coronary	eqtl	1.3e-02	-0.82	14:67527392:C:T
Prostate	eqtl	1.6e-02	+0.50	14:67337658:C:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
143734	5.2130	890
143735	0.2444	90
143733	0.1244	61
143736	0.0640	27
143732	0.0083	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.23	gold quality
secondary oocyte	CL:0000655	97.54	gold quality
mucosa of transverse colon	UBERON:0004991	94.68	gold quality
right adrenal gland cortex	UBERON:0035827	92.38	gold quality
right adrenal gland	UBERON:0001233	91.92	gold quality
gingival epithelium	UBERON:0001949	91.76	gold quality
left adrenal gland	UBERON:0001234	91.27	gold quality
adrenal tissue	UBERON:0018303	91.25	gold quality
cervix squamous epithelium	UBERON:0006922	91.00	silver quality
left adrenal gland cortex	UBERON:0035825	91.00	gold quality
corpus epididymis	UBERON:0004359	90.95	gold quality
rectum	UBERON:0001052	90.87	gold quality
adrenal cortex	UBERON:0001235	90.44	gold quality
gingiva	UBERON:0001828	89.94	gold quality
adrenal gland	UBERON:0002369	89.78	gold quality
jejunal mucosa	UBERON:0000399	89.11	gold quality
right lobe of thyroid gland	UBERON:0001119	89.09	gold quality
duodenum	UBERON:0002114	88.79	gold quality
left lobe of thyroid gland	UBERON:0001120	88.75	gold quality
epithelial cell of pancreas	CL:0000083	88.68	gold quality
colonic mucosa	UBERON:0000317	88.54	gold quality
ileal mucosa	UBERON:0000331	88.36	gold quality
pancreatic ductal cell	CL:0002079	88.35	silver quality
thyroid gland	UBERON:0002046	88.34	gold quality
right lobe of liver	UBERON:0001114	88.01	gold quality
squamous epithelium	UBERON:0006914	87.96	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.65	gold quality
skin of abdomen	UBERON:0001416	86.88	gold quality
lower esophagus mucosa	UBERON:0035834	86.71	gold quality
skin of leg	UBERON:0001511	86.22	gold quality
zone of skin	UBERON:0000014	85.79	gold quality
esophagus squamous epithelium	UBERON:0006920	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.65	gold quality
upper leg skin	UBERON:0004262	84.55	gold quality
epithelium of esophagus	UBERON:0001976	84.51	gold quality
esophagus mucosa	UBERON:0002469	83.82	gold quality
liver	UBERON:0002107	83.44	gold quality
cauda epididymis	UBERON:0004360	83.16	gold quality
palpebral conjunctiva	UBERON:0001812	83.11	gold quality
hair follicle	UBERON:0002073	82.98	silver quality
cervix epithelium	UBERON:0004801	81.29	silver quality
trabecular bone tissue	UBERON:0002483	81.26	gold quality
tongue squamous epithelium	UBERON:0006919	81.23	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	81.12	gold quality
transverse colon	UBERON:0001157	81.02	gold quality
blood	UBERON:0000178	80.61	gold quality
skin of hip	UBERON:0001554	79.98	gold quality
amniotic fluid	UBERON:0000173	79.67	gold quality
small intestine	UBERON:0002108	79.59	gold quality
islet of Langerhans	UBERON:0000006	79.48	gold quality
jejunum	UBERON:0002115	79.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.23	gold quality
bone marrow	UBERON:0002371	79.03	gold quality
body of pancreas	UBERON:0001150	78.52	gold quality
nasal cavity mucosa	UBERON:0001826	78.39	gold quality
epithelium of nasopharynx	UBERON:0001951	78.28	gold quality
pancreas	UBERON:0001264	78.16	gold quality
nasal cavity epithelium	UBERON:0005384	77.93	gold quality
germinal epithelium of ovary	UBERON:0001304	77.07	gold quality
renal glomerulus	UBERON:0000074	76.86	gold quality
mouth mucosa	UBERON:0003729	76.74	gold quality
mammalian vulva	UBERON:0000997	76.65	gold quality
metanephric glomerulus	UBERON:0004736	76.58	gold quality
metanephros cortex	UBERON:0010533	76.51	gold quality
oral cavity	UBERON:0000167	76.40	gold quality
minor salivary gland	UBERON:0001830	76.04	gold quality
metanephros	UBERON:0000081	75.82	gold quality
cortex of kidney	UBERON:0001225	75.67	gold quality
intestine	UBERON:0000160	75.63	gold quality
saliva-secreting gland	UBERON:0001044	75.17	gold quality
prostate gland	UBERON:0002367	74.94	gold quality
colonic epithelium	UBERON:0000397	74.43	gold quality
caecum	UBERON:0001153	74.30	gold quality
large intestine	UBERON:0000059	74.25	gold quality
vagina	UBERON:0000996	74.15	gold quality
vermiform appendix	UBERON:0001154	73.92	gold quality
tonsil	UBERON:0002372	73.79	gold quality
colon	UBERON:0001155	73.62	gold quality
nephron tubule	UBERON:0001231	73.59	silver quality
type B pancreatic cell	CL:0000169	73.38	gold quality
body of stomach	UBERON:0001161	73.32	gold quality
kidney epithelium	UBERON:0004819	73.19	gold quality
gall bladder	UBERON:0002110	72.92	gold quality
stomach	UBERON:0000945	72.32	gold quality
olfactory bulb	UBERON:0002264	71.69	gold quality
periodontal ligament	UBERON:0008266	71.65	silver quality
adult mammalian kidney	UBERON:0000082	71.56	gold quality
kidney	UBERON:0002113	71.41	gold quality
parotid gland	UBERON:0001831	71.34	gold quality
thymus	UBERON:0002370	71.10	gold quality
penis	UBERON:0000989	71.06	gold quality
caput epididymis	UBERON:0004358	70.87	gold quality
stromal cell of endometrium	CL:0002255	70.55	gold quality
bone marrow cell	CL:0002092	70.43	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.34	gold quality
upper arm skin	UBERON:0004263	70.19	silver quality
urinary bladder	UBERON:0001255	70.03	gold quality
oviduct epithelium	UBERON:0004804	69.45	silver quality
pharyngeal mucosa	UBERON:0000355	68.35	silver quality
mucosa of urinary bladder	UBERON:0001259	68.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.47

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Small intestine	tissue	30.7	high
Epididymis	tissue	30.5	low
Adrenal gland	tissue	30.3	medium
Duodenum	tissue	27.8	medium
Liver	tissue	27.7	high
Rectum	tissue	26.9	medium
Skin 1	tissue	25.1	medium
Colon	tissue	23.5	low
Thyroid gland	tissue	22.0	low
Thymus	tissue	21.3
Stomach 1	tissue	19.5	low
Bone marrow	tissue	11.9	medium
Urinary bladder	tissue	11.3	low
Esophagus	tissue	8.8	low
Vagina	tissue	8.0	not detected
Parathyroid gland	tissue	6.5	low
Prostate	tissue	5.9	low
Appendix	tissue	5.2	medium
Tonsil	tissue	5.1	medium
Pancreas	tissue	4.8	high
Kidney	tissue	4.7	high
Seminal vesicle	tissue	4.0	low
Salivary gland	tissue	4.0	medium
Breast	tissue	3.7	low
Gallbladder	tissue	3.7	medium
Olfactory bulb	tissue	3.4
Testis	tissue	2.9	low
Ovary	tissue	2.4	low
Superior colliculi	tissue	2.4
Cervix	tissue	1.8	low
Cerebral cortex	tissue	1.7	medium
Hippocampal formation	tissue	1.7
Occipital cortex	tissue	1.7
Ventral forebrain	tissue	1.6
Fallopian tube	tissue	1.6	low
Prefrontal cortex	tissue	1.5
Lung	tissue	1.5	high
Endometrium 1	tissue	1.4	low
Hypothalamus	tissue	1.4
Placenta	tissue	1.4	medium
Pituitary gland	tissue	1.3
Pons	tissue	1.3
Motor cortex	tissue	1.3
Basal ganglia	tissue	1.3	not detected
Entorhinal cortex	tissue	1.3
Septum	tissue	1.3
Retrosplenial cortex	tissue	1.3
Smooth muscle	tissue	1.2	not detected
Putamen	tissue	1.2
Amygdala	tissue	1.2
Retrosplenial and cingulate cortex	tissue	1.2
Periaqueductal gray	tissue	1.2
Insular cortex	tissue	1.2
Medulla oblongata	tissue	1.1
Substantia nigra	tissue	1.1
Somatosensory cortex	tissue	1.1
Temporal cortex	tissue	1.1
Midbrain	tissue	0.9
Thalamus	tissue	0.8
Cerebellum	tissue	0.7	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Vermis (1.8), Dorsal hippocampus (1.7), Flocculonodular lobe (1.4), Anterior thalamic nucleus, ventral (1.2), Cerebellar cortex (1.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

Targeting PLEK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 34 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-8089	97.74	66.21	1698

Functional genomics

gnomAD constraint: pLI 2.15e-05, LOEUF 0.924, missense Z 0.931 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000216446 — one region, missense o/e 0.89.

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

Organism	Symbol	Gene ID
danio_rerio	plek2	ENSDARG00000012789
mus_musculus	Plek2	ENSMUSG00000021118
rattus_norvegicus	Plek2	ENSRNOG00000010098

Paralogs (1): PLEK (ENSG00000115956)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1351466) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sternum morphology	1
abnormal megakaryocyte differentiation	1
enlarged spleen	1
anemia	1
abnormal skin morphology	1
abnormal cell differentiation	1
abnormal granulocyte differentiation	1
increased cellular sensitivity to oxidative stress	1
increased erythroblast number	1
abnormal reticulocyte cell number	1
impaired bone marrow erythropoiesis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Chlorocebus aethiops	Q76MY7	99.8%	Diamond
Canis lupus familiaris	Q6Q308	94.0%	Diamond
Bos taurus	Q3ZBA3	92.2%	Diamond
Xenopus laevis	Q6PA69	60.8%	Diamond
Dictyostelium discoideum	Q54KA7	54.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GPHN	protein-coding	10243
TMEM229B	protein-coding	161145
EIF2S1	protein-coding	1965
PLEKHH1	protein-coding	57475
MIR5694	ncRNA	100847064
VTI1B	protein-coding	10490
LINC02290	ncRNA	105370540
RDH12	protein-coding	145226
GARIN2	protein-coding	161142
ZFYVE26	protein-coding	23503
ARG2	protein-coding	384
CCDC196	protein-coding	440184
RDH11	protein-coding	51109
ATP6V1D	protein-coding	51382
PIGH	protein-coding	5283
PALS1	protein-coding	64398

Protein

Protein identifiers

Pleckstrin-2 — Q9NYT0 (reviewed: Q9NYT0)

All UniProt accessions (5): G3V337, Q9NYT0, 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)

ID	Name	Type
IPR000591	DEP_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR037369	PLEK2_DEP	Domain
IPR037370	Pleckstrin	Family

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 by resolution:

PDB	Title	Method	Resolution (Å)
1X1G	Solution structure of the C-terminal PH domain of human pleckstrin 2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYT0-F1	85.98	0.55

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; cytosol

Antibody reliability (HPA): IH enhanced · IF uncertain

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)

Type	Positions
N-acetylmethionine	1
Phosphoserine	120

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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), erythrocyte enucleation (GO:0043131), positive regulation of plasma membrane bounded cell projection assembly (GO:0120034)

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 (4): cytoskeleton (GO:0005856), plasma membrane (GO:0005886), lamellipodium membrane (GO:0031258), membrane (GO:0016020)

GO top-level categories

19 GO namespaces:

Category	Terms
phosphatidylinositol phosphate binding	2
phosphatidylinositol bisphosphate binding	2
cytoskeleton organization	1
actin filament-based process	1
intracellular anatomical structure	1
signal transduction	1
enucleate erythrocyte maturation	1
enucleation	1
positive regulation of cell projection organization	1
positive regulation of cellular component biogenesis	1
plasma membrane bounded cell projection assembly	1
regulation of plasma membrane bounded cell projection assembly	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
lamellipodium	1
cell projection membrane	1
leading edge membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 2,692 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEK2	MCF2	P10911	964
PLEK2	OSBP	P22059	906
PLEK2	PLCD1	P51178	897
PLEK2	SRC	P12931	868
PLEK2	CYTH1	Q15438	868
PLEK2	AKT1	P31749	851
PLEK2	RABIF	P47224	838
PLEK2	CDC42	P21181	831
PLEK2	CYTH3	O43739	816
PLEK2	RHOA	P06749	811
PLEK2	SERPINA4	P29622	805
PLEK2	PIK3CG	P48736	795
PLEK2	RASA1	P20936	790
PLEK2	PLEKHA3	Q9HB20	783
PLEK2	ARF1	P10947	781

IntAct

BioGRID (25 interactions; top human partners by supporting records): INPPL1 (Affinity Capture-Western; 4 records), MYC (Affinity Capture-MS; 3 records), EGFR (Affinity Capture-Western; 2 records), ANLN (Affinity Capture-MS), DDRGK1 (Co-fractionation), DGCR8 (Co-fractionation), GNB2 (Proximity Label-MS), HADHA (Cross-Linking-MS (XL-MS)), KLC4 (Co-fractionation), KRAS (Proximity Label-MS), MUS81 (Synthetic Growth Defect), NR2C2 (Affinity Capture-MS), PIP4K2A (Proximity Label-MS), RAC1 (Proximity Label-MS), RNF128 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for PLEK2: 1 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 768):

Position(s)	Effect	Δscore	Sites
14:67387457–67387458	acceptor_loss	1.0000	6
14:67393176	donor_gain	1.0000
14:67393246	acceptor_gain	1.0000
14:67395584–67395585	acceptor_loss	1.0000	5
14:67395586	acceptor_gain	1.0000
14:67397660–67397661	donor_loss	1.0000	5
14:67397827–67397828	acceptor_loss	1.0000	6
14:67412016–67412017	donor_loss	1.0000	5
14:67387463	acceptor_gain	0.9900
14:67388303–67388304	acceptor_loss	0.9900	6

AlphaMissense

833 missense substitutions predicted likely pathogenic (of 2,311 scored), across 212 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F269	8	0.960	0.998
F26	8	0.954	0.998
F322	8	0.927	0.999
D93	8	0.915	0.981
D215	8	0.907	0.973
H259	8	0.897	0.977
D306	8	0.812	0.950
N263	8	0.806	0.975
H16	8	0.803	0.932
W264	7	0.997	1.000
W21	7	0.995	0.999
W345	7	0.995	1.000
W95	7	0.992	0.999
W25	7	0.976	0.994
K256	7	0.963	1.000
F10	7	0.961	0.993
K13	7	0.956	0.999
W167	7	0.914	0.984
R272	7	0.869	0.986
H279	7	0.867	0.979

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	4.21e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000201

Disease associations

OMIM: gene MIM:608007 | disease phenotypes:

GWAS associations

8 associations:

Study	Trait	p-value
GCST90002387_371	Immature fraction of reticulocytes	9e-45
GCST90002386_365	High light scatter reticulocyte percentage of red cells	1e-21
GCST90002385_454	High light scatter reticulocyte count	2e-21
GCST004628_151	Immature fraction of reticulocytes	7e-20
GCST004611_48	High light scatter reticulocyte count	4e-12
GCST004612_172	High light scatter reticulocyte percentage of red cells	5e-12
GCST007256_1	Broad depression or major depressive disorder (recurrent)	4e-9
GCST004024_1	Depressive symptom measurement or major depressive disorder	4e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
bisphenol S	affects cotreatment, increases methylation, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression	1
chloropicrin	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression	1
Aldehydes	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.