PLCB2

Summary

PLCB2 (phospholipase C beta 2, HGNC:9055) is a protein-coding gene on chromosome 15q15.1, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 (Q00722). The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.

The protein encoded by this gene is a phosphodiesterase that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. The encoded protein is activated by G proteins and has been shown to be involved in the type 2 taste receptor signal transduction pathway. In addition, nuclear factor kappa B can regulate the transcription of this gene, whose protein product is also an important regulator of platelet responses.

Source: NCBI Gene 5330 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 186 total
• MANE Select transcript: NM_004573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9055
Approved symbol	PLCB2
Name	phospholipase C beta 2
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38135
Ensembl gene	ENSG00000137841
Ensembl biotype	protein_coding
OMIM	604114
Entrez	5330

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 9 retained_intron, 1 nonsense_mediated_decay

ENST00000260402, ENST00000456256, ENST00000543785, ENST00000557821, ENST00000558409, ENST00000558505, ENST00000558588, ENST00000559381, ENST00000559618, ENST00000559634, ENST00000559671, ENST00000560009, ENST00000560093, ENST00000560701, ENST00000561378, ENST00000882413, ENST00000882414, ENST00000949765, ENST00000949766

RefSeq mRNA: 4 — MANE Select: NM_004573 NM_001284297, NM_001284298, NM_001284299, NM_004573

CCDS: CCDS42020, CCDS61591, CCDS61592, CCDS73704

Canonical transcript exons

ENST00000260402 — 32 exons

Exon	Start	End
ENSE00000883837	40291265	40291487
ENSE00000883838	40291606	40291650
ENSE00000883839	40291849	40291924
ENSE00002553740	40307589	40307935
ENSE00003474513	40292926	40293025
ENSE00003515496	40290025	40290082
ENSE00003518026	40296746	40296908
ENSE00003562922	40292339	40292443
ENSE00003601213	40290761	40290837
ENSE00003601655	40298798	40298964
ENSE00003609604	40290577	40290672
ENSE00003639564	40289272	40289358
ENSE00003640725	40287909	40288918
ENSE00003644079	40291018	40291183
ENSE00003661643	40298562	40298708
ENSE00003713611	40293560	40293724
ENSE00003713906	40294936	40295060
ENSE00003714681	40295201	40295285
ENSE00003716101	40301957	40302032
ENSE00003717477	40302136	40302189
ENSE00003720112	40304001	40304078
ENSE00003725288	40298223	40298380
ENSE00003725836	40302270	40302349
ENSE00003726196	40296522	40296634
ENSE00003726697	40297877	40297959
ENSE00003728414	40303288	40303356
ENSE00003728629	40299128	40299228
ENSE00003738776	40302469	40302609
ENSE00003741994	40292064	40292158
ENSE00003744138	40297521	40297605
ENSE00003745681	40296296	40296392
ENSE00003750862	40294266	40294420

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 11.6306 / max 362.0980, expressed in 688 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149487	6.0751	621
149485	3.4609	480
149486	1.4193	339
149484	0.5868	226
149482	0.0691	24
149483	0.0194	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.40	gold quality
monocyte	CL:0000576	98.41	gold quality
mononuclear cell	CL:0000842	97.77	gold quality
leukocyte	CL:0000738	97.59	gold quality
spleen	UBERON:0002106	96.75	gold quality
blood	UBERON:0000178	94.50	gold quality
bone marrow cell	CL:0002092	94.11	gold quality
lymph node	UBERON:0000029	93.55	gold quality
vermiform appendix	UBERON:0001154	93.41	gold quality
upper lobe of left lung	UBERON:0008952	91.83	gold quality
right lung	UBERON:0002167	91.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.33	gold quality
gall bladder	UBERON:0002110	91.03	gold quality
right uterine tube	UBERON:0001302	90.58	gold quality
upper lobe of lung	UBERON:0008948	90.50	gold quality
right coronary artery	UBERON:0001625	89.70	gold quality
nucleus accumbens	UBERON:0001882	89.64	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.62	gold quality
sural nerve	UBERON:0015488	89.53	gold quality
caecum	UBERON:0001153	89.37	gold quality
spinal cord	UBERON:0002240	88.93	gold quality
bone marrow	UBERON:0002371	87.84	gold quality
caudate nucleus	UBERON:0001873	87.59	gold quality
small intestine	UBERON:0002108	87.43	gold quality
putamen	UBERON:0001874	86.61	gold quality
mucosa of transverse colon	UBERON:0004991	86.10	gold quality
right adrenal gland cortex	UBERON:0035827	85.85	gold quality
omental fat pad	UBERON:0010414	85.72	gold quality
peritoneum	UBERON:0002358	85.66	gold quality
right adrenal gland	UBERON:0001233	85.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting PLCB2, 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-4692	100.00	67.32	2066
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-5581-5P	97.91	66.50	965

Literature-anchored findings (GeneRIF, showing 31)

• up-regulated during granulocytic differenetiation of normal and leukemic hematopoietic progenitors (PMID:12050180)
• interacts with mitogen-activated protein kinase kinase 3. (PMID:12054652)
• Conformation determines signal transduction of PLCB2 by Gbeta (PMID:12388553)
• the recognition site for Rac GTPases was localized to the pleckstrin homology (PH) domain of PLC-beta2, and this PH domain is fully sufficient to selectively interact with the active versions of the Rac GTPases, but not with other similar Rho GTPases. (PMID:12657629)
• Pleckstrin homology domains of phospholipases C-beta and -delta confer activation through a common site (PMID:12761218)
• results support a model in which PLCbeta2 suppresses the basal catalytic activity of PLCdelta1, which is relieved by binding of Gbetagamma subunits to PLCbeta2 allowing for amplified calcium signals (PMID:15509571)
• there are two modes of PLC binding to Gbetagamma through the catalytic domain, where interactions with the amino-terminal coiled-coil domain are inhibitory, and interactions with the Galpha subunit switch II binding surface are stimulatory (PMID:15611108)
• Fluid shear flow experiments with MG-63 lacking PLC beta2 revealed a significantly higher level of cells losing attachment to coverslips and a significantly lower number of cells increasing intracellular free calcium. (PMID:15939402)
• Data indicate that PLC-beta2 expression correlates highly with breast cancer malignancy and suggest that it can be included, as an independent marker, among the prognostic indicators in current use. (PMID:16525635)
• May constitute a molecular marker of breast tumor cells able to monitor the progression to invasive cancers and a target for novel therapeutic breast cancer strategies. (PMID:17429106)
• PLCB2 activity on actin-associated polyphosphoinositides promotes migration of differentiating tumoral myeloid precursors. (PMID:17478077)
• Both PLC-beta2 isoforms are expressed at the protein level in platelets. In transfected CV-1 cells, PLC-beta2a is more enriched in the nuclei than PLC-beta2b. The two variants may have different effects in cell proliferation and differentiation. (PMID:17497434)
• all IGF2 actions were exerted predominantly through IGF2R-linked G(i) protein signaling and required intracellular Ca(2+) mobilization induced by the beta2 isoform of phospholipase C in endothelial progenitor cell homing (PMID:18832656)
• associated with Libman-Sacks endocarditis, cardiac manifestation of SLE (PMID:19089657)
• receptor stimulation leads to sequestration of recycling endosomes in a classical protein kinase C- and phospholipase D-dependent manner (PMID:19525236)
• Data show that activation of PLCbeta(2) by alpha(q) and beta1gamma2 differ from activation by Rac2 and from each other. (PMID:20007712)
• Rac1 activates phospholipase Cdelta1 through phospholipase Cbeta2 (PMID:20530480)
• WDR36 acts as a scaffold protein tethering a G-protein-coupled receptor, Galphaq and phospholipase C beta 2 in a signalling complex (PMID:21940795)
• GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4. (PMID:22728827)
• gamma-synuclein has a role in promoting a more robust G protein Galphaq activation of PLCbeta2 (PMID:22905097)
• PLCbeta2 is enriched in the cytosol. (PMID:23006664)
• WDR26 functions as a scaffolding protein to promote PLCbeta2 membrane translocation and interaction with Gbetagamma, thereby enhancing PLCbeta2 activation in leukocytes. (PMID:23625927)
• In this study, we show that staphylococcal enterotoxin B activates a Galphaq and PLCbeta2-dependent pathway in human T cells (PMID:23690479)
• high expression of CD133 in triple-negative breast cancer (TNBC)-derived cells correlates with high invasive potential; aggressive properties of CD133high cells are mitigated by PLC-beta2 which down-modulates expression of CD133 and may play a role in preventing metastatic progression of CD133 positive TNBC (PMID:24330829)
• Neuropeptide Y decreased PLCB2 expression in HUVECs. (PMID:24903829)
• Gnb isoforms control a signaling pathway comprising Rac1, Plcbeta2, and Plcbeta3 leading to LFA-1 activation and neutrophil arrest in vivo (PMID:26468229)
• Hypoxia modulates the expression of PLC-beta-2 in breast tumor cells in a phenotype-related manner, since a decrease of the protein was observed in the BT-474 and MCF7 cell lines while an increase was revealed in MDA-MB-231 cells as a consequence of low oxygen availability. (PMID:26785288)
• this work adds substantial information about the role of PLC-beta2 in invasive breast tumors, demonstrating that its up-regulation in cells with a basal-B triple-negative phenotype is sufficient to down-modulate the expression of surface antigens crucial for malignancy and to reduce the number of cells with a stem-like phenotype. (PMID:28870198)
• High PLCB2 expression is associated with breast cancer. (PMID:30582225)
• Knockdown of PLCB2 expression reduces melanoma cell viability and promotes melanoma cell apoptosis by altering Ras/Raf/MAPK signals. (PMID:31746389)
• PLCbeta2 Promotes VEGF-Induced Vascular Permeability. (PMID:35861069)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000090381
mus_musculus	Plcb2	ENSMUSG00000040061
rattus_norvegicus	Plcb2	ENSRNOG00000058337
drosophila_melanogaster	sl	FBGN0003416
drosophila_melanogaster	Plc21C	FBGN0004611
caenorhabditis_elegans		WBGENE00004038
caenorhabditis_elegans		WBGENE00004039
caenorhabditis_elegans		WBGENE00004045

Paralogs (14): PLCB4 (ENSG00000101333), PLCH1 (ENSG00000114805), PLCD4 (ENSG00000115556), PLCL1 (ENSG00000115896), PLCG1 (ENSG00000124181), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCB3 (ENSG00000149782), PLCL2 (ENSG00000154822), PLCD3 (ENSG00000161714), PLCB1 (ENSG00000182621), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 — Q00722 (reviewed: Q00722)

Alternative names: Phosphoinositide phospholipase C-beta-2, Phospholipase C-beta-2

All UniProt accessions (4): Q00722, H0YKR9, H0YNI4, Q9BVT6

UniProt curated annotations — full annotation on UniProt →

Function. The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway by promoting RASGRP4 activation by DAG, to promote neutrophil functional responses.

Subunit / interactions. Interacts with RAC1. Forms a complex composed of at least WDR26, a G-beta:gamma unit, and PLCB2.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Miscellaneous. The receptor-mediated activation of PLC-beta-2 is most effectively mediated by one G-protein alpha subunit, alpha-16.

Isoforms (3)

UniProt ID	Names	Canonical?
Q00722-1	1	yes
Q00722-2	2
Q00722-3	3

RefSeq proteins (4): NP_001271226, NP_001271227, NP_001271228, NP_004564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000909	PLipase_C_PInositol-sp_X_dom	Domain
IPR001192	PI-PLC_fam	Family
IPR001711	PLipase_C_Pinositol-sp_Y	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR014815	PLC-beta_C	Domain
IPR016280	PLC-beta	Family
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR028403	PLC-beta2_cat	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037862	PLC-beta_PH	Domain
IPR042531	PLC-beta_C_sf	Homologous_superfamily
IPR046969	PLCbeta2_EF	Domain
IPR053945	PLCB1-4-like_EFh	Domain

Pfam: PF00168, PF00387, PF00388, PF08703, PF17787, PF22631

Enzyme classification (BRENDA):

• EC 3.1.4.11 — phosphoinositide phospholipase C (BRENDA: 69 organisms, 175 substrates, 159 inhibitors, 27 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4,5-BISPHOSPHATE	0.006–0.45	8
PHOSPHATIDYLINOSITOL	0.012–100	7
1-PHOSPHATIDYL-1D-MYO-INOSITOL	0.058–18.7	6
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.031–0.182	3
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.031	1

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H(+) (RHEA:33179)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+) (RHEA:43484)

UniProt features (98 total): helix 34, strand 28, turn 8, sequence variant 5, binding site 4, domain 3, compositionally biased region 3, region of interest 3, active site 2, splice variant 2, sequence conflict 2, chain 1, modified residue 1, mutagenesis site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2ZKM	X-RAY DIFFRACTION	1.62
2FJU	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00722-F1	84.71	0.63

Functional residue map

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

Catalytic / active sites (2): 327; 374

Ligand- & substrate-binding residues (4): 328; 357; 359; 408

Post-translational modifications (1): 953

Mutagenesis-validated functional residues (1):

Position	Phenotype
52	strongly reduces interaction with rac1.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-112043	PLC beta mediated events
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-399997	Acetylcholine regulates insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418217	G beta:gamma signalling through PLC beta
R-HSA-434316	Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion
R-HSA-500657	Presynaptic function of Kainate receptors
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste

MSigDB gene sets: 319 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, PID_S1P_S1P1_PATHWAY, FREAC2_01, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_CELL_CHEMOTAXIS, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_SECRETORY_GRANULE, MODULE_45, AREB6_03, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, FOXO4_01, FOXO1_01, CAGCTG_AP4_Q5

GO Biological Process (13): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), phospholipid metabolic process (GO:0006644), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), lipid catabolic process (GO:0016042), phosphatidylinositol metabolic process (GO:0046488), phosphatidylinositol-mediated signaling (GO:0048015), release of sequestered calcium ion into cytosol (GO:0051209), cell chemotaxis (GO:0060326), lipid metabolic process (GO:0006629), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), sensory perception of bitter taste (GO:0050913)

GO Molecular Function (10): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), C-type glycerophospholipase activity (GO:0004629), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), G-protein beta/gamma-subunit complex binding (GO:0031683), phosphatidylinositol phospholipase C activity (GO:0120548), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), G-protein beta/gamma-subunit complex (GO:0031680), neuronal dense core vesicle (GO:0098992)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
G-protein mediated events	1
Inositol phosphate metabolism	1
Regulation of insulin secretion	1
Beta-catenin independent WNT signaling	1
GPCR downstream signalling	1
G-protein beta:gamma signalling	1
Free fatty acids regulate insulin secretion	1
Activation of kainate receptors upon glutamate binding	1
Sensory perception of taste	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
signal transduction	2
intracellular anatomical structure	2
C-type glycerophospholipase activity	2
cellular anatomical structure	2
cytoplasm	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
organophosphate metabolic process	1
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
catabolic process	1
phosphorus metabolic process	1
intracellular signal transduction	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of taste	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
metal ion binding	1
lipid binding	1
protein-containing complex binding	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cation binding	1
protein-containing complex	1
dense core granule	1

Protein interactions and networks

STRING

1968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCB2	GNAT3	A8MTJ3	988
PLCB2	TRPM5	Q9NZQ8	979
PLCB2	GNAQ	P50148	919
PLCB2	TAS2R46	P59540	898
PLCB2	TAS2R4	Q9NYW5	888
PLCB2	TAS2R38	P59533	878
PLCB2	TAS1R3	Q7RTX0	877
PLCB2	TAS2R43	P59537	867
PLCB2	TAS1R2	Q8TE23	866
PLCB2	GNB4	Q9HAV0	836
PLCB2	SUCLG2	Q96I99	803
PLCB2	GNB3	P16520	799
PLCB2	CXCR2	P25025	789
PLCB2	GNB1	P04697	785
PLCB2	GNG2	P59768	765

IntAct

130 interactions, top by confidence:

A	B	Type	Score
CTNNAL1	PLCB2	psi-mi:“MI:0915”(physical association)	0.580
CTNNAL1	DTNB	psi-mi:“MI:0914”(association)	0.500
PLCB2	RAC1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
RHPN1	PLCB2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	GOPC	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB2	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	PLCB2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (25): TRPM7 (Two-hybrid), PLCB2 (Protein-peptide), PLCB2 (Proximity Label-MS), PLCB2 (Affinity Capture-MS), PLCB2 (Affinity Capture-RNA), PLCB2 (Reconstituted Complex), PLCB2 (Affinity Capture-Western), MAP2K3 (Two-hybrid), MAP2K3 (Affinity Capture-Western), MAP2K6 (Affinity Capture-Western), MAPK14 (Affinity Capture-Western), PLCB2 (PCA), PLCB2 (Negative Genetic), PLCB3 (Negative Genetic), PLCB2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0FGR9, A2AP18, A3KGF7, A5D6R3, F8VPU2, O14976, O15068, O43304, O75038, O89040, O94887, P10688, P10895, P19687, P21671, P33402, P51178, P51432, P97874, Q00722, Q01970, Q0V9N0, Q15111, Q3U5C8, Q3USB7, Q4KWH5, Q4KWH8, Q4R6L3, Q5QNQ6, Q5RAB8, Q5RJH2, Q5SVR0, Q62688, Q62711, Q63406, Q64096, Q66K14, Q69Z98, Q86TI0, Q8IWQ3

Diamond homologs: A2AP18, A3KGF7, A5D6R3, G5EBH0, G5EFI8, O75038, O89040, P10687, P10688, P10894, P10895, P21671, P25455, P51178, P51432, Q00722, Q01970, Q07722, Q15111, Q15147, Q1RML2, Q2VRL0, Q32NH8, Q3USB7, Q4KWH5, Q4KWH8, Q4R6L3, Q5FX52, Q5RET0, Q62688, Q62711, Q6NMA7, Q7YRU3, Q86YW0, Q8K2J0, Q8K394, Q8K3R3, Q8K4D7, Q8K4S1, Q8L706

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GNB1	up-regulates	PLCB2	binding
PLCB2	“up-regulates quantity”	“1D-myo-inositol 1,4,5-trisphosphate(6-)”	“chemical modification”
PLCB2	“up-regulates quantity”	superoxide
GNB/GNG	up-regulates	PLCB2

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
Ras activation upon Ca2+ influx through NMDA receptor	5	49.2×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.9×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.9×	3e-06
Long-term potentiation	5	41.0×	5e-06
Assembly and cell surface presentation of NMDA receptors	9	39.4×	1e-10
Neurexins and neuroligins	10	34.0×	6e-11
Protein-protein interactions at synapses	6	27.5×	3e-06
Formation of the dystrophin-glycoprotein complex (DGC)	5	26.6×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	69.2×	6e-14
protein localization to synapse	6	54.7×	1e-07
receptor clustering	7	52.0×	2e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.3×	6e-08
cell-cell adhesion	10	12.1×	1e-06
protein-containing complex assembly	8	10.8×	5e-05
regulation of small GTPase mediated signal transduction	5	8.6×	7e-03
protein localization to plasma membrane	6	7.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	149
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

5234 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40289268:TTA:T	donor_loss	1.0000
15:40289269:TA:T	donor_loss	1.0000
15:40289270:ACCTG:A	donor_loss	1.0000
15:40289271:C:A	donor_loss	1.0000
15:40289271:CCTG:C	donor_gain	1.0000
15:40289292:T:C	donor_gain	1.0000
15:40289354:GTCAT:G	acceptor_gain	1.0000
15:40289355:TCAT:T	acceptor_gain	1.0000
15:40289356:CAT:C	acceptor_gain	1.0000
15:40289356:CATC:C	acceptor_gain	1.0000
15:40289357:AT:A	acceptor_gain	1.0000
15:40289358:TC:T	acceptor_loss	1.0000
15:40289359:C:CA	acceptor_loss	1.0000
15:40289359:C:CC	acceptor_gain	1.0000
15:40289360:T:A	acceptor_loss	1.0000
15:40289363:G:C	acceptor_gain	1.0000
15:40289363:G:GC	acceptor_gain	1.0000
15:40289369:G:C	acceptor_gain	1.0000
15:40289369:G:GC	acceptor_gain	1.0000
15:40289373:A:AC	acceptor_gain	1.0000
15:40289373:A:C	acceptor_gain	1.0000
15:40289377:C:CT	acceptor_gain	1.0000
15:40289385:C:CT	acceptor_gain	1.0000
15:40289386:A:T	acceptor_gain	1.0000
15:40290571:GCTCA:G	donor_loss	1.0000
15:40290573:TCAC:T	donor_loss	1.0000
15:40290574:CACCT:C	donor_loss	1.0000
15:40290575:A:C	donor_loss	1.0000
15:40290576:C:CA	donor_loss	1.0000
15:40290576:CCT:C	donor_gain	1.0000

AlphaMissense

7855 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40294949:G:C	N631K	1.000
15:40294949:G:T	N631K	1.000
15:40295000:G:C	N614K	1.000
15:40295000:G:T	N614K	1.000
15:40295017:G:T	R609S	1.000
15:40295028:G:T	P605H	1.000
15:40295037:C:G	R602P	1.000
15:40295039:G:C	S601R	1.000
15:40295039:G:T	S601R	1.000
15:40295041:T:G	S601R	1.000
15:40296849:C:A	K461N	1.000
15:40296849:C:G	K461N	1.000
15:40297887:G:C	H410D	1.000
15:40297888:G:C	N409K	1.000
15:40297888:G:T	N409K	1.000
15:40297892:T:A	E408V	1.000
15:40298254:C:T	G375D	1.000
15:40298256:A:C	H374Q	1.000
15:40298256:A:T	H374Q	1.000
15:40298258:G:C	H374D	1.000
15:40298295:C:A	W361C	1.000
15:40298295:C:G	W361C	1.000
15:40298297:A:G	W361R	1.000
15:40298297:A:T	W361R	1.000
15:40298302:T:A	D359V	1.000
15:40298302:T:G	D359A	1.000
15:40298305:A:G	L358P	1.000
15:40298307:C:A	E357D	1.000
15:40298307:C:G	E357D	1.000
15:40298567:A:G	L331P	1.000

dbSNP variants (sampled 300 via entrez): RS1000187040 (15:40287858 C>A,G), RS1000208258 (15:40292853 C>G,T), RS1000221627 (15:40285926 A>G), RS1000572357 (15:40285621 G>A,T), RS1000638631 (15:40300300 G>A), RS1000822837 (15:40306233 A>G), RS1000848161 (15:40304382 T>C), RS1001021964 (15:40294195 A>T), RS1001089522 (15:40305884 C>G), RS1001128939 (15:40309721 C>A,G), RS1001373623 (15:40293848 C>G,T), RS1001387392 (15:40288958 G>A), RS1001435175 (15:40298153 C>A,G), RS1001538266 (15:40297568 T>C), RS1001617926 (15:40295310 A>G)

Disease associations

OMIM: gene MIM:604114 | disease phenotypes: MIM:157900

GenCC curated gene-disease

Mondo (2): Mobius syndrome (MONDO:0008006), thrombocytopenia (MONDO:0002049)

Orphanet (1): Moebius syndrome (Orphanet:570)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002539_24	Schizophrenia	4.000000e-09
GCST006803_39	Schizophrenia	2.000000e-08
GCST009879_1	Coronary artery disease	1.000000e-29
GCST010476_1	Myocardial infarction	9.000000e-26
GCST010477_2	Hypertension	3.000000e-07
GCST010478_5	Chronic kidney disease	5.000000e-08
GCST010836_1	Ischemic stroke	4.000000e-09
GCST90002398_229	Neutrophil count	6.000000e-09
GCST90002407_585	White blood cell count	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Phosphoinositide-specific phospholipase C

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
quercitrin	affects expression	1
terbufos	decreases methylation	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
edelfosine	affects localization, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Cytarabine	affects localization, decreases reaction	1
Dapsone	decreases reaction, increases phosphorylation	1
Doxorubicin	decreases expression	1
Dust	decreases expression	1
Fonofos	decreases methylation	1
Estradiol	increases expression	1
Naled	affects expression	1
Ozone	affects expression, increases abundance	1
Paraquat	decreases reaction, increases phosphorylation	1
Parathion	decreases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8T9	Ubigene HCT 116 PLCB2 KO	Cancer cell line	Male
CVCL_E0L5	Ubigene HeLa PLCB2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT