PLEKHO2

Summary

PLEKHO2 (pleckstrin homology domain containing O2, HGNC:30026) is a protein-coding gene on chromosome 15q22.31, encoding Pleckstrin homology domain-containing family O member 2 (Q8TD55).

Predicted to be involved in macrophage apoptotic process. Predicted to be located in extracellular region and ficolin-1-rich granule lumen.

Source: NCBI Gene 80301 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 85 total — 1 pathogenic
• MANE Select transcript: NM_025201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30026
Approved symbol	PLEKHO2
Name	pleckstrin homology domain containing O2
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761K2312, PP1628, pp9099
Ensembl gene	ENSG00000241839
Ensembl biotype	protein_coding
Entrez	80301

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000323544, ENST00000616065, ENST00000866141, ENST00000925882, ENST00000925883, ENST00000925884, ENST00000925885

RefSeq mRNA: 2 — MANE Select: NM_025201 NM_001195059, NM_025201

CCDS: CCDS10196, CCDS73739

Canonical transcript exons

ENST00000323544 — 6 exons

Exon	Start	End
ENSE00001245279	64864899	64868002
ENSE00001412207	64841915	64842028
ENSE00003572664	64861477	64861575
ENSE00003615993	64859894	64859998
ENSE00003644329	64848593	64848742
ENSE00003676807	64854921	64855037

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 95.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.6378 / max 1216.2656, expressed in 1788 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147189	30.6378	1788

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	95.83	gold quality
granulocyte	CL:0000094	95.36	gold quality
blood	UBERON:0000178	94.58	gold quality
leukocyte	CL:0000738	93.82	gold quality
monocyte	CL:0000576	93.67	gold quality
mononuclear cell	CL:0000842	93.61	gold quality
upper lobe of left lung	UBERON:0008952	91.00	gold quality
gall bladder	UBERON:0002110	90.51	gold quality
upper lobe of lung	UBERON:0008948	90.39	gold quality
decidua	UBERON:0002450	90.28	gold quality
right adrenal gland	UBERON:0001233	90.19	gold quality
omental fat pad	UBERON:0010414	90.19	gold quality
right lobe of thyroid gland	UBERON:0001119	90.18	gold quality
peritoneum	UBERON:0002358	90.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.99	gold quality
lower esophagus	UBERON:0013473	89.95	gold quality
right adrenal gland cortex	UBERON:0035827	89.94	gold quality
left adrenal gland	UBERON:0001234	89.91	gold quality
left uterine tube	UBERON:0001303	89.86	gold quality
left adrenal gland cortex	UBERON:0035825	89.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.69	gold quality
left lobe of thyroid gland	UBERON:0001120	89.67	gold quality
right lung	UBERON:0002167	89.31	gold quality
adrenal cortex	UBERON:0001235	89.22	gold quality
stromal cell of endometrium	CL:0002255	89.05	gold quality
thyroid gland	UBERON:0002046	88.95	gold quality
lymph node	UBERON:0000029	88.81	gold quality
tendon of biceps brachii	UBERON:0008188	88.69	gold quality
adrenal gland	UBERON:0002369	88.68	gold quality
vermiform appendix	UBERON:0001154	88.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting PLEKHO2, 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-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-6873-3P	100.00	71.42	2626
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-605-3P	99.88	69.22	1833

Literature-anchored findings (GeneRIF, showing 1)

• The miR-106b/NR2F2-AS1/PLEKHO2 Axis Regulates Migration and Invasion of Colorectal Cancer through the MAPK Pathway. (PMID:34070923)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekho2	ENSDARG00000016774
mus_musculus	Plekho2	ENSMUSG00000050721
rattus_norvegicus	Plekho2	ENSRNOG00000029242

Paralogs (1): PLEKHO1 (ENSG00000023902)

Protein

Protein identifiers

Pleckstrin homology domain-containing family O member 2 — Q8TD55 (reviewed: Q8TD55)

Alternative names: Pleckstrin homology domain-containing family Q member 1

All UniProt accessions (1): Q8TD55

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TD55-1	1	yes
Q8TD55-2	2

RefSeq proteins (2): NP_001181988, NP_079477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR043448	PKHO1/2	Family

Pfam: PF00169

UniProt features (20 total): modified residue 11, compositionally biased region 3, chain 1, domain 1, splice variant 1, sequence variant 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD55-F1	63.47	0.20

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 (11): 235, 237, 238, 273, 298, 311, 390, 468, 164, 167, 232

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 189 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MODULE_45, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_LEUKOCYTE_APOPTOTIC_PROCESS, MODULE_88, MODULE_60, MODULE_38, NAGASHIMA_EGF_SIGNALING_UP, GOCC_SECRETORY_VESICLE, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D

GO Biological Process (1): macrophage apoptotic process (GO:0071888)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inflammatory cell apoptotic process	1
myeloid cell apoptotic process	1
leukocyte apoptotic process	1
binding	1
cellular anatomical structure	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHO2	C12orf56	Q8IXR9	396
PLEKHO2	C16orf46	Q6P387	368
PLEKHO2	TMC7	Q7Z402	355
PLEKHO2	CSRNP2	Q9H175	331
PLEKHO2	AADACL4	Q5VUY2	323
PLEKHO2	CCDC183	Q5T5S1	316
PLEKHO2	ARMCX5	Q6P1M9	313
PLEKHO2	RNF148	Q8N7C7	306
PLEKHO2	THEMIS2	Q5TEJ8	304
PLEKHO2	TMEM217B	A0A494BZU4	296
PLEKHO2	TMEM217	Q8N7C4	293
PLEKHO2	CYTH4	Q9UIA0	290
PLEKHO2	CMTR1	Q8N1G2	289
PLEKHO2	CRACDL	Q6NV74	285
PLEKHO2	SPAG11A	Q6PDA7	277

IntAct

20 interactions, top by confidence:

A	B	Type	Score
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
PLEKHO2	CAPZB	psi-mi:“MI:0914”(association)	0.640
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
Capza1		psi-mi:“MI:0915”(physical association)	0.400
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
PLTP	CLGN	psi-mi:“MI:0914”(association)	0.350
PLEKHO2	MAP3K6	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TACC3	TNC	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (71): PLEKHO2 (Affinity Capture-MS), RNF20 (Affinity Capture-MS), RNF40 (Affinity Capture-MS), VEZT (Affinity Capture-MS), ANAPC7 (Affinity Capture-MS), FLAD1 (Affinity Capture-MS), TACC3 (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), MAP3K6 (Affinity Capture-MS), FAM184A (Affinity Capture-MS), UBR2 (Affinity Capture-MS), BBS7 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZM56, A2AG50, A2AI08, A2AJI0, A5D7K1, D4A4L4, E1C2Q8, F1LR10, O00515, O14529, O75128, O88573, O88735, P51825, P57016, Q14244, Q32LQ1, Q3KQU3, Q3U2K0, Q5JTD0, Q5NBX1, Q5PR69, Q5R7F9, Q5XHX2, Q5ZIA2, Q5ZJJ1, Q68DK7, Q6IPM2, Q6NV74, Q6NZF1, Q6PDH0, Q6PDM1, Q6PG95, Q6ZU35, Q86UU1, Q8CCJ4, Q8K124, Q8N7J2, Q8TD55, Q96PV7

Diamond homologs: A4IFK0, A4IG55, Q32LQ1, Q53GL0, Q5BJM5, Q5F3C8, Q8K124, Q8TD55, Q9JIY0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Membrane Trafficking	5	12.4×	5e-04
Vesicle-mediated transport	5	11.6×	6e-04
Signaling by Rho GTPases	5	11.4×	6e-04
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	5	11.2×	6e-04
Adaptive Immune System	5	9.9×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	78
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442892	GRCh37/hg19 15q11.2-26.3(chr15:22770422-102429112)	Pathogenic

SpliceAI

878 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64842023:G:GT	donor_gain	1.0000
15:64842025:GGAG:G	donor_gain	1.0000
15:64842026:GAGG:G	donor_gain	1.0000
15:64842026:GAGGT:G	donor_loss	1.0000
15:64842027:AGGT:A	donor_loss	1.0000
15:64842028:GGTG:G	donor_loss	1.0000
15:64842030:T:G	donor_loss	1.0000
15:64848741:AGG:A	donor_loss	1.0000
15:64848743:G:GA	donor_loss	1.0000
15:64848744:T:G	donor_loss	1.0000
15:64854919:A:AG	acceptor_gain	1.0000
15:64854919:AG:A	acceptor_gain	1.0000
15:64854919:AGGAT:A	acceptor_gain	1.0000
15:64854920:G:GC	acceptor_gain	1.0000
15:64854920:G:GG	acceptor_gain	1.0000
15:64854920:GG:G	acceptor_gain	1.0000
15:64854920:GGA:G	acceptor_gain	1.0000
15:64854920:GGAT:G	acceptor_gain	1.0000
15:64854920:GGATG:G	acceptor_gain	1.0000
15:64855035:AAGG:A	donor_loss	1.0000
15:64855035:AAGGT:A	donor_loss	1.0000
15:64855036:AGG:A	donor_loss	1.0000
15:64855037:GGTA:G	donor_loss	1.0000
15:64855038:G:A	donor_loss	1.0000
15:64855038:GT:G	donor_loss	1.0000
15:64855039:T:A	donor_loss	1.0000
15:64859994:ATGAG:A	donor_loss	1.0000
15:64859995:TGAGG:T	donor_loss	1.0000
15:64859996:GAGG:G	donor_loss	1.0000
15:64859997:AG:A	donor_loss	1.0000

AlphaMissense

3163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64855009:T:C	F84S	0.999
15:64859910:T:C	F99S	0.999
15:64859942:T:A	W110R	0.999
15:64859942:T:C	W110R	0.999
15:64854969:T:C	C71R	0.997
15:64855015:T:C	L86P	0.997
15:64859944:G:C	W110C	0.997
15:64859944:G:T	W110C	0.997
15:64848723:T:C	L48P	0.996
15:64859943:G:C	W110S	0.996
15:64859955:T:C	L114P	0.996
15:64848696:G:C	R39P	0.995
15:64854952:T:A	L65Q	0.995
15:64854971:C:G	C71W	0.995
15:64855015:T:A	L86Q	0.995
15:64848698:T:G	Y40D	0.993
15:64848702:T:C	L41P	0.993
15:64848723:T:A	L48Q	0.993
15:64854960:T:G	Y68D	0.992
15:64859955:T:A	L114H	0.992
15:64848661:G:C	K27N	0.991
15:64848661:G:T	K27N	0.991
15:64855015:T:G	L86R	0.991
15:64859942:T:G	W110G	0.991
15:64848686:T:A	W36R	0.990
15:64848686:T:C	W36R	0.990
15:64854970:G:A	C71Y	0.990
15:64859967:T:C	I118T	0.990
15:64861509:T:A	H139Q	0.990
15:64861509:T:G	H139Q	0.990

dbSNP variants (sampled 300 via entrez): RS1000185570 (15:64845689 C>G,T), RS1000196867 (15:64845434 G>A), RS1000261199 (15:64852964 A>G), RS1000425325 (15:64858973 T>C), RS1000565511 (15:64850037 G>A,C), RS1000617918 (15:64850318 C>G,T), RS1000682271 (15:64852738 A>G), RS1000717414 (15:64852666 G>A,T), RS1000793822 (15:64851497 G>C,T), RS1001114892 (15:64841511 T>C,G), RS1001124080 (15:64843878 C>G), RS1001319458 (15:64853927 C>G), RS1001423325 (15:64860174 G>A), RS1001565856 (15:64840566 C>G,T), RS1001583452 (15:64866256 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): internal carotid artery stenosis (MONDO:0005189)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000975_4	LDL cholesterol	9.000000e-06
GCST005991_38	Platelet count	6.000000e-10
GCST90002401_96	Platelet distribution width	7.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	increases methylation, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
licochalcone B	increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzene	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01591005	PHASE3	COMPLETED	SONOlysis in Prevention of Brain Infarctions dUring Carotid Stenting and caroTid EndaRterectomy
NCT03121209	PHASE3	ACTIVE_NOT_RECRUITING	Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)
NCT00737334	Not specified	COMPLETED	EEG, Cerebral Oximetry, and Arterial to Jugular Venous Lactate to Assess Cerebral Ischemia During Carotid Endarterectomy
NCT01877174	Not specified	COMPLETED	MICHI™ Neuroprotection System (NPS+f) Filter Debris Analysis Study (The F-1 Study)
NCT02398734	Not specified	COMPLETED	SONOlysis in Prevention of Brain InfaRctions During Internal Carotid Endarterectomy
NCT02794974	Not specified	COMPLETED	Ultrasound-guided Intermediate Cervical Plexus Block
NCT05260229	Not specified	UNKNOWN	The Observation About the Effects of Internal Carotid Artery Stenosis on Fundus Vessels and the Changes of Fundus Vessels After Interventional Therapy