PLEKHB2

Summary

PLEKHB2 (pleckstrin homology domain containing B2, HGNC:19236) is a protein-coding gene on chromosome 2q21.1, encoding Pleckstrin homology domain-containing family B member 2 (Q96CS7). Involved in retrograde transport of recycling endosomes.

Enables phosphatidylinositol-3,4,5-trisphosphate binding activity. Predicted to be involved in regulation of cell differentiation. Predicted to be located in recycling endosome membrane. Predicted to be active in membrane.

Source: NCBI Gene 55041 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_001100623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19236
Approved symbol	PLEKHB2
Name	pleckstrin homology domain containing B2
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	EVT2, FLJ20783
Ensembl gene	ENSG00000115762
Ensembl biotype	protein_coding
OMIM	618452
Entrez	55041

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 34 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000234115, ENST00000403716, ENST00000404460, ENST00000409158, ENST00000409279, ENST00000409612, ENST00000438882, ENST00000439822, ENST00000482225, ENST00000487980, ENST00000628582, ENST00000693505, ENST00000893315, ENST00000893316, ENST00000893317, ENST00000893318, ENST00000893319, ENST00000893320, ENST00000893321, ENST00000893322, ENST00000893323, ENST00000893324, ENST00000893325, ENST00000893326, ENST00000918036, ENST00000918037, ENST00000918038, ENST00000918039, ENST00000918040, ENST00000918041, ENST00000918042, ENST00000918043, ENST00000950349, ENST00000950350, ENST00000950351, ENST00000950352

RefSeq mRNA: 13 — MANE Select: NM_001100623 NM_001100623, NM_001267062, NM_001267063, NM_001267064, NM_001267065, NM_001267066, NM_001267067, NM_001267068, NM_001309448, NM_001309450, NM_001309451, NM_001309452, NM_017958

CCDS: CCDS2166, CCDS46413, CCDS58729, CCDS58730, CCDS58731, CCDS74576, CCDS74577

Canonical transcript exons

ENST00000693505 — 8 exons

Exon	Start	End
ENSE00000776212	131126684	131126786
ENSE00000827002	131132902	131132991
ENSE00001003386	131130721	131130760
ENSE00001557464	131140167	131140275
ENSE00003501600	131125753	131125905
ENSE00003595262	131120934	131120978
ENSE00003771378	131105336	131105398
ENSE00003923893	131146637	131149845

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.1904 / max 664.7939, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22541	44.1071	1815
22540	13.0832	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	98.79	gold quality
endothelial cell	CL:0000115	98.46	gold quality
superior vestibular nucleus	UBERON:0007227	98.06	gold quality
inferior vagus X ganglion	UBERON:0005363	97.93	gold quality
substantia nigra pars compacta	UBERON:0001965	97.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.62	gold quality
cerebellar vermis	UBERON:0004720	97.59	gold quality
dorsal root ganglion	UBERON:0000044	97.56	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.42	gold quality
palpebral conjunctiva	UBERON:0001812	97.39	gold quality
ventral tegmental area	UBERON:0002691	97.37	gold quality
renal medulla	UBERON:0000362	97.36	gold quality
nephron tubule	UBERON:0001231	97.18	gold quality
adrenal tissue	UBERON:0018303	97.17	gold quality
parietal lobe	UBERON:0001872	97.09	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.09	gold quality
superior frontal gyrus	UBERON:0002661	97.09	gold quality
middle frontal gyrus	UBERON:0002702	97.09	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.06	gold quality
postcentral gyrus	UBERON:0002581	97.01	gold quality
orbitofrontal cortex	UBERON:0004167	97.00	gold quality
medulla oblongata	UBERON:0001896	96.99	gold quality
frontal pole	UBERON:0002795	96.94	gold quality
ileal mucosa	UBERON:0000331	96.93	gold quality
amniotic fluid	UBERON:0000173	96.89	gold quality
adult mammalian kidney	UBERON:0000082	96.81	gold quality
middle temporal gyrus	UBERON:0002771	96.74	gold quality
colonic mucosa	UBERON:0000317	96.70	gold quality
subthalamic nucleus	UBERON:0001906	96.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	422.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

147 targeting PLEKHB2, 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-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
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-4692	100.00	67.32	2066
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 3)

• Data show that depletion of evt-2 or masking of intracellular PS suppressed membrane traffic from REs to the Golgi. (PMID:21911378)
• The crystal structure at 1.75 A resolution of an apo form of human evectin-2 pleckstrin homology domain, in which the ligand-binding site is free from crystal packing and is thus appropriate for comparison with the structure of the complex, is reported. (PMID:22281740)
• Knockdown of evectin-2 (a recycling endosome-resident protein) suppresses nuclear localization of YAP and YAP-dependent transcription. Evectin-2 knockdown reduces the ubiquitination and increased the level of Lats1. (PMID:29093443)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhb2	ENSDARG00000013928
mus_musculus	Plekhb2	ENSMUSG00000026123
rattus_norvegicus	Plekhb2	ENSRNOG00000014162

Paralogs (1): PLEKHB1 (ENSG00000021300)

Protein

Protein identifiers

Pleckstrin homology domain-containing family B member 2 — Q96CS7 (reviewed: Q96CS7)

Alternative names: Evectin-2

All UniProt accessions (4): Q96CS7, A0A0A0MSE9, A0A0A0MSI4, B7WPA5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in retrograde transport of recycling endosomes.

Subcellular location. Recycling endosome membrane.

Domain organisation. The PH domain specifically binds phosphatidylserine, which is enriched in recycling endosome membranes, it doesn’t recognize PIPs.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96CS7-1	1	yes
Q96CS7-2	2
Q96CS7-3	3
Q96CS7-4	4
Q96CS7-5	5
Q96CS7-6	6

RefSeq proteins (13): NP_001094093, NP_001253991, NP_001253992, NP_001253993, NP_001253994, NP_001253995, NP_001253996, NP_001253997, NP_001296377, NP_001296379, NP_001296380, NP_001296381, NP_060428 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR039680	PLEKHB1/2	Family

Pfam: PF00169

UniProt features (21 total): strand 8, splice variant 5, helix 4, chain 1, domain 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3AJ4	X-RAY DIFFRACTION	1
3VIA	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CS7-F1	69.97	0.47

Functional residue map

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

Ligand- & substrate-binding residues (1): 20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 216 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, SHEPARD_BMYB_MORPHOLINO_UP, TAATAAT_MIR126, KAAB_FAILED_HEART_ATRIUM_DN, BROWNE_HCMV_INFECTION_16HR_UP, GOLDRATH_ANTIGEN_RESPONSE, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, WANG_LMO4_TARGETS_DN, MODULE_256, TIEN_INTESTINE_PROBIOTICS_24HR_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, SENESE_HDAC1_TARGETS_UP, MODULE_333

GO Biological Process (1): regulation of cell differentiation (GO:0045595)

GO Molecular Function (2): phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), protein binding (GO:0005515)

GO Cellular Component (3): membrane (GO:0016020), recycling endosome membrane (GO:0055038), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
anion binding	1
phosphatidylinositol phosphate binding	1
binding	1
cellular anatomical structure	1
endosome membrane	1
recycling endosome	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHB2	CELF4	Q9BZC1	608
PLEKHB2	PLEK2	Q9NYT0	602
PLEKHB2	PLEK	P08567	599
PLEKHB2	ATP8A1	Q9Y2Q0	541
PLEKHB2	AMER3	Q8N944	455
PLEKHB2	NPIPA7	E9PJI5	435
PLEKHB2	TMEM87B	Q96K49	378
PLEKHB2	PLEKHH3	Q7Z736	372
PLEKHB2	NUDCD2	Q8WVJ2	370
PLEKHB2	FAM168B	A1KXE4	370
PLEKHB2	FAM76A	Q8TAV0	367
PLEKHB2	EHD1	Q9H4M9	352
PLEKHB2	ARHGEF4	Q9NR80	350
PLEKHB2	CELF5	Q8N6W0	348
PLEKHB2	AGBL5	Q8NDL9	348

IntAct

198 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
PLEKHB2	STAM2	psi-mi:“MI:0915”(physical association)	0.720
PLEKHB2	CDA	psi-mi:“MI:0915”(physical association)	0.720
DAZAP2	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.720
PLEKHB2	C1orf94	psi-mi:“MI:0915”(physical association)	0.720
STAM2	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.720
CDA	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.720
C1orf94	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.720
PLEKHB2	DAZAP2	psi-mi:“MI:0915”(physical association)	0.720
BHLHE40	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
EPN1	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
PLEKHB2	BHLHE40	psi-mi:“MI:0915”(physical association)	0.560
PLEKHB2	EPN1	psi-mi:“MI:0915”(physical association)	0.560
HGS	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
FAM168A	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
PITX1	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
TAX1BP1	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
EPN2	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (89): PLEKHB2 (Two-hybrid), PLEKHB2 (Two-hybrid), PLEKHB2 (Two-hybrid), PLEKHB2 (Two-hybrid), PLEKHB2 (Two-hybrid), C1orf94 (Two-hybrid), PLEKHB2 (Biochemical Activity), PLEKHB2 (Affinity Capture-MS), CST6 (Affinity Capture-MS), ITCH (Affinity Capture-MS), NCCRP1 (Affinity Capture-MS), ALOXE3 (Affinity Capture-MS), PLEKHB2 (Affinity Capture-MS), PLEKHB2 (Affinity Capture-MS), CST6 (Affinity Capture-MS)

ESM2 similar proteins: B6SGC5, O95415, P0C0T0, P28662, P50636, Q32L83, Q3C2P8, Q3T0A9, Q3TWL2, Q4R5H7, Q4R6W2, Q58D45, Q5BJ83, Q5E9E8, Q5EAU3, Q5F3S2, Q5PPK1, Q5PPM8, Q5PQS5, Q5R4K6, Q5RDN2, Q5U2U6, Q5XID0, Q5XKA6, Q5Y171, Q66I51, Q66JG9, Q6DC04, Q6DIE4, Q6GMG8, Q6NYG4, Q6NYK3, Q6P828, Q7Z698, Q7Z699, Q86T03, Q8AVW3, Q8N114, Q8QGW7, Q8VIH7

Diamond homologs: Q5F3S2, Q5R4K6, Q96CS7, Q9QYE9, Q9QZC7, Q9UF11, Q9WU68

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
InlB-mediated entry of Listeria monocytogenes into host cell	6	84.6×	2e-09
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	6	84.6×	2e-09
Regulation of NF-kappa B signaling	7	82.2×	1e-10
MAP3K8 (TPL2)-dependent MAPK1/3 activation	6	79.3×	2e-09
TICAM1, RIP1-mediated IKK complex recruitment	7	77.9×	2e-10
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	6	66.8×	6e-09
IKK complex recruitment mediated by RIP1	7	64.4×	6e-10
Negative regulation of MET activity	6	57.7×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	5	23.2×	3e-04
negative regulation of canonical NF-kappaB signal transduction	7	15.2×	1e-04
epidermis development	5	13.3×	3e-03
positive regulation of canonical NF-kappaB signal transduction	7	6.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3001 predictions. Top by Δscore:

Variant	Effect	Δscore
2:131105395:GCAG:G	donor_gain	1.0000
2:131105399:G:C	donor_loss	1.0000
2:131105399:G:GG	donor_gain	1.0000
2:131107514:A:G	donor_gain	1.0000
2:131107539:G:GT	donor_gain	1.0000
2:131120977:GA:G	donor_gain	1.0000
2:131120979:G:GG	donor_gain	1.0000
2:131120989:G:GT	donor_gain	1.0000
2:131121021:G:T	donor_gain	1.0000
2:131125749:CCAG:C	acceptor_loss	1.0000
2:131125749:CCAGG:C	acceptor_gain	1.0000
2:131125750:CA:C	acceptor_loss	1.0000
2:131125750:CAGG:C	acceptor_gain	1.0000
2:131125751:A:AG	acceptor_gain	1.0000
2:131125751:A:AT	acceptor_loss	1.0000
2:131125751:AG:A	acceptor_gain	1.0000
2:131125751:AGGT:A	acceptor_gain	1.0000
2:131125752:G:GT	acceptor_gain	1.0000
2:131125752:GG:G	acceptor_gain	1.0000
2:131125752:GGT:G	acceptor_gain	1.0000
2:131125752:GGTA:G	acceptor_gain	1.0000
2:131125752:GGTAC:G	acceptor_gain	1.0000
2:131125848:GA:G	donor_gain	1.0000
2:131125897:A:T	donor_gain	1.0000
2:131125901:TCGGG:T	donor_gain	1.0000
2:131125903:GGG:G	donor_gain	1.0000
2:131125904:GG:G	donor_gain	1.0000
2:131125904:GGG:G	donor_gain	1.0000
2:131125905:GG:G	donor_gain	1.0000
2:131125906:G:GA	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000041185 (2:131123393 A>G), RS1000047920 (2:131126454 A>T), RS1000061250 (2:131129908 A>G), RS1000124105 (2:131114670 G>A,C), RS1000182518 (2:131120245 A>G), RS1000190227 (2:131105746 C>G), RS1000295354 (2:131147282 G>A,T), RS1000367233 (2:131111304 C>G), RS1000392444 (2:131133102 C>A,T), RS1000394134 (2:131123890 C>T), RS1000467371 (2:131108096 AT>A), RS1000522759 (2:131107460 G>C), RS1000559556 (2:131149209 C>T), RS1000592375 (2:131121588 C>G,T), RS1000622373 (2:131115090 T>C)

Disease associations

OMIM: gene MIM:618452 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
uranyl acetate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
trichostatin A	affects expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
ICG 001	increases 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	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dietary Carbohydrates	increases expression	1
Doxorubicin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Phenobarbital	affects expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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