PLCB3

Summary

PLCB3 (phospholipase C beta 3, HGNC:9056) is a protein-coding gene on chromosome 11q13.1, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 (Q01970). Catalyzes the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).

This gene encodes a member of the phosphoinositide phospholipase C beta enzyme family that catalyze the production of the secondary messengers diacylglycerol and inositol 1,4,5-triphosphate from phosphatidylinositol in G-protein-linked receptor-mediated signal transduction. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5331 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondylometaphyseal dysplasia with corneal dystrophy (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 17
• Clinical variants (ClinVar): 176 total — 1 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• MANE Select transcript: NM_000932

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9056
Approved symbol	PLCB3
Name	phospholipase C beta 3
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000149782
Ensembl biotype	protein_coding
OMIM	600230
Entrez	5331

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 retained_intron

ENST00000279230, ENST00000325234, ENST00000536243, ENST00000540288, ENST00000885806, ENST00000885807, ENST00000885808, ENST00000885809, ENST00000885811, ENST00000885813, ENST00000885814, ENST00000885815, ENST00000922180, ENST00000922181

RefSeq mRNA: 3 — MANE Select: NM_000932 NM_000932, NM_001184883, NM_001316314

CCDS: CCDS53654, CCDS8064

Canonical transcript exons

ENST00000279230 — 31 exons

Exon	Start	End
ENSE00000992481	64261581	64261665
ENSE00000992482	64261952	64262076
ENSE00000992483	64262407	64262561
ENSE00000992484	64262647	64262808
ENSE00000992485	64263498	64263597
ENSE00000992491	64265886	64266039
ENSE00000992492	64266126	64266202
ENSE00000992493	64266315	64266404
ENSE00000992494	64266495	64266552
ENSE00000992495	64267185	64267271
ENSE00001195654	64265310	64265502
ENSE00001195667	64265192	64265227
ENSE00001195674	64264951	64265104
ENSE00001195737	64261400	64261496
ENSE00001195745	64260029	64260234
ENSE00001195752	64259058	64259244
ENSE00001195762	64258885	64258969
ENSE00001195771	64258473	64258713
ENSE00001195781	64256618	64256764
ENSE00001195792	64256376	64256542
ENSE00001195800	64255721	64255821
ENSE00001195811	64255541	64255616
ENSE00001195819	64255396	64255449
ENSE00001195828	64255234	64255313
ENSE00001195833	64254898	64255038
ENSE00001195840	64254748	64254816
ENSE00001195847	64254415	64254492
ENSE00002238417	64251530	64251748
ENSE00002302404	64267353	64267923
ENSE00003530559	64264021	64264112
ENSE00003628348	64263691	64263795

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 95.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6359 / max 228.3749, expressed in 1799 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114915	17.6286	1799
114916	0.0074	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	95.26	gold quality
mucosa of transverse colon	UBERON:0004991	94.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.60	gold quality
tendon of biceps brachii	UBERON:0008188	93.42	gold quality
small intestine	UBERON:0002108	92.44	gold quality
duodenum	UBERON:0002114	92.17	gold quality
esophagus mucosa	UBERON:0002469	91.13	gold quality
buccal mucosa cell	CL:0002336	90.05	gold quality
transverse colon	UBERON:0001157	89.57	gold quality
right adrenal gland	UBERON:0001233	88.42	gold quality
ectocervix	UBERON:0012249	88.29	gold quality
esophagus	UBERON:0001043	88.09	gold quality
left adrenal gland cortex	UBERON:0035825	87.97	gold quality
stromal cell of endometrium	CL:0002255	87.85	gold quality
right adrenal gland cortex	UBERON:0035827	87.83	gold quality
right coronary artery	UBERON:0001625	87.76	gold quality
left adrenal gland	UBERON:0001234	87.67	gold quality
body of uterus	UBERON:0009853	87.62	gold quality
left uterine tube	UBERON:0001303	87.45	gold quality
right ovary	UBERON:0002118	87.16	gold quality
left coronary artery	UBERON:0001626	86.93	gold quality
endocervix	UBERON:0000458	86.79	gold quality
ascending aorta	UBERON:0001496	86.74	gold quality
thoracic aorta	UBERON:0001515	86.64	gold quality
ileal mucosa	UBERON:0000331	86.31	gold quality
vagina	UBERON:0000996	86.26	gold quality
adrenal cortex	UBERON:0001235	86.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.87	gold quality
aorta	UBERON:0000947	85.86	gold quality
intestine	UBERON:0000160	85.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	19.48
E-ANND-3	yes	9.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting PLCB3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-4751	98.80	64.95	525

Literature-anchored findings (GeneRIF, showing 30)

• PLC beta 3 and PLC beta 1 bind to calmodulin (PMID:12821674)
• findings demonstrated that G-protein-activated phospholipase C-beta interacts with cell polarity proteins Par3 and Par6 to form protein complexes and to mediate downstream signal transduction (PMID:15782111)
• reduced Ca(2+) signaling in high glucose cannot be explained by reduced Ca(2+) stores but is due to conventional PKC-dependent phosphorylation and inactivation of PLC-beta(3) (PMID:15998840)
• Homodimerization of PLC-beta3 and PLC-beta1 isoenzymes was observed but heterodimerization of these isoenzymes was not detected. (PMID:16763092)
• Fission of transport carriers at the trans-Golgi network is dependent on specifically PLCbeta3, which is necessary to activate PKCeta and PKD in that Golgi compartment, via diacylglycerol production. (PMID:17492941)
• both negative crosstalk from the cAMP/PRKA pathway and a negative feedback loop in the oxytocin/G protein/PLCB pathway involving PRKC operate in myometrial cells (PMID:18322273)
• PLCbeta3 may provide a selective target for inhibiting Ca(2+) responses to mediators of inflammation, including C5a, UDP, PAF, and LPA (PMID:18411281)
• VEGF, specifically through VEGFR2, induces phosphorylation of two serine residues on PLCbeta3. (PMID:19295129)
• study describe the structure of PLC-beta3 in an activated complex with Galphaq, which together with supporting biochemical and physiological analyses reveals its mechanism of transmembrane signaling (PMID:20966218)
• Activation of hPLCbeta3 by U73122 required covalent modification of cysteines as evidenced by the observation that enzyme activation was attenuated by thiol-containing nucleophiles, l-cysteine and glutathione. (PMID:21266572)
• Studies indicate that the complex between the effector protein phospholipase C-beta3 (PLC-beta3) and its activator, Galpha(q), suggests that several effectors independently evolved a structurally similar helix-turn-helix segment for G protein recognition. (PMID:21304157)
• Data demonstrate that PLCB3, by regulating intracellular calcium transients, plays a relevant role in amplifying the expression and release of IL-8, the major chemokine recruiting neutrophils in CF airway lungs. (PMID:21411730)
• Stromal cell-derived factor-1 signaling via the CXCR4-TCR heterodimer uses PLC-beta3 to activate the Ras-ERK pathway and increase intracellular calcium ion concentrations (PMID:21705626)
• PDZ domain-containing 1 (PDZK1) protein regulates phospholipase C-beta3 (PLC-beta3)-specific activation of somatostatin by forming a ternary complex with PLC-beta3 and somatostatin receptors. (PMID:22528496)
• GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4. (PMID:22728827)
• PLCbeta3 is enriched in the cytosol. (PMID:23006664)
• phospholipase C-beta3 structure reveals the role of the its distal C-terminal domain (PMID:23377541)
• the M3 muscarinic receptor maximizes the efficiency of PLCbeta3 signaling beyond its canonical role as a guanine nucleotide exchange factor for Galpha. (PMID:24596086)
• This study provides an understanding of the structural basis for the PDZ-mediated NHERF1-PLCbeta3 interaction that could prove valuable in selective drug design against CXCR2-related cancers. (PMID:24642259)
• membranes are integral for the activation of PLC-beta isozymes by diverse modulators. (PMID:25193662)
• Gnb isoforms control a signaling pathway comprising Rac1, Plcbeta2, and Plcbeta3 leading to LFA-1 activation and neutrophil arrest in vivo (PMID:26468229)
• the MCP1-induced cortactin phosphorylation is dependent on PLCb3-mediated PKC activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2 (PMID:26490115)
• We propose that unliganded PLC-beta exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-beta modulates Gbetagamma access to its binding site. (PMID:27002154)
• These results indicate that the mechanism by which Galphaq and PLC-beta3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined. (PMID:28842497)
• Data suggest that 300-residue C-terminal domain of PLCB3 promotes adsorption to phospholipid monolayer/membrane bilayer and is required for spatial organization/adsorption of PLCB3 on membrane surface; defects in phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis alter monolayer adsorption, thus, suggesting role of active site in this process; PLCB3 is preferentially adsorbed to region of bilayer enriched with PIP2. (PMID:28945350)
• A homozygous loss of function variant in PLCB3 is associated with corneal dystrophy, developmental delay and spondylometaphyseal dysplasia. (PMID:29122926)
• These results, besides identifying S845L as a loss-of-function variant, strengthen the importance of targeting PLCB3 to mitigate the cystic fibrosis inflammatory response in bronchial epithelial cells without blunting the immune response. (PMID:29668297)
• This study reveals detailed mechanistic insight into the role of ORP4L in PLCbeta3 redistribution from storage within the nucleus to the plasma membrane via RAN activation and interaction with VAPA in Jurkat T-cells. (PMID:30237164)
• Intramolecular electrostatic interactions contribute to phospholipase Cbeta3 autoinhibition. (PMID:31254604)
• Phospholipase C controls chloride-dependent short-circuit current in human bronchial epithelial cells. (PMID:33236921)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcb3	ENSDARG00000068246
mus_musculus	Plcb3	ENSMUSG00000024960
rattus_norvegicus	Plcb3	ENSRNOG00000021150
drosophila_melanogaster	Plc21C	FBGN0004611

Paralogs (14): PLCB4 (ENSG00000101333), PLCH1 (ENSG00000114805), PLCD4 (ENSG00000115556), PLCL1 (ENSG00000115896), PLCG1 (ENSG00000124181), PLCB2 (ENSG00000137841), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCL2 (ENSG00000154822), PLCD3 (ENSG00000161714), PLCB1 (ENSG00000182621), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 — Q01970 (reviewed: Q01970)

Alternative names: Phosphoinositide phospholipase C-beta-3, Phospholipase C-beta-3

All UniProt accessions (1): Q01970

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Key transducer of G protein-coupled receptor signaling: activated by G(q)/G(11) G alpha proteins downstream of G protein-coupled receptors activation. 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 SHANK2. Interacts with LPAR2.

Subcellular location. Cytoplasm. Membrane. Nucleus.

Disease relevance. Spondylometaphyseal dysplasia with corneal dystrophy (SMDCD) [MIM:618961] An autosomal recessive disorder characterized by postnatal growth deficiency, profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by G(q)/G(11) G alpha proteins in response to ligand-binding to G protein-coupled receptors.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01970-1	1	yes
Q01970-2	2

RefSeq proteins (3): NP_000923, NP_001171812, NP_001303243 (=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
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037862	PLC-beta_PH	Domain
IPR042531	PLC-beta_C_sf	Homologous_superfamily
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 (121 total): strand 41, helix 39, modified residue 7, mutagenesis site 7, compositionally biased region 5, turn 5, region of interest 4, domain 3, sequence conflict 3, active site 2, sequence variant 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
7SQ2	X-RAY DIFFRACTION	2.6
4QJ3	X-RAY DIFFRACTION	3
4QJ4	X-RAY DIFFRACTION	3.3
8EMX	ELECTRON MICROSCOPY	3.3
8UQO	ELECTRON MICROSCOPY	3.37
8UQN	ELECTRON MICROSCOPY	3.4
4QJ5	X-RAY DIFFRACTION	3.41
8EMW	ELECTRON MICROSCOPY	3.5
8EMV	ELECTRON MICROSCOPY	3.6
4GNK	X-RAY DIFFRACTION	4
9Y7H	ELECTRON MICROSCOPY	4.4
9YAP	ELECTRON MICROSCOPY	4.5
9YAO	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01970-F1	83.47	0.64

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): 332; 379

Post-translational modifications (7): 2, 474, 490, 495, 537, 926, 1105

Mutagenesis-validated functional residues (7):

Position	Phenotype
258	reduced ability to promote the gtpase activity of g(q)/g(11) g alpha proteins.
260	reduced ability to promote the gtpase activity of g(q)/g(11) g alpha proteins.
855	abolished ability to transduce g(q)/g(11) g alpha signaling.
859	abolished ability to transduce g(q)/g(11) g alpha signaling without affecting the phospholipase activity.
861	abolished ability to transduce g(q)/g(11) g alpha signaling.
862	abolished ability to transduce g(q)/g(11) g alpha signaling.
863	abolished ability to transduce g(q)/g(11) g alpha signaling.

Function

Pathways and Gene Ontology

Reactome pathways

8 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

MSigDB gene sets: 321 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GCANCTGNY_MYOD_Q6, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, AP2_Q3, GGGTGGRR_PAX4_03, chr11q13, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (12): regulation of systemic arterial blood pressure (GO:0003073), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208), lipid catabolic process (GO:0016042), phosphatidylinositol metabolic process (GO:0046488), phosphatidylinositol-mediated signaling (GO:0048015), release of sequestered calcium ion into cytosol (GO:0051209), lipid metabolic process (GO:0006629), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway (GO:0140582)

GO Molecular Function (11): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), C-type glycerophospholipase activity (GO:0004629), calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), cadherin binding (GO:0045296), molecular adaptor activity (GO:0060090), phosphatidylinositol phospholipase C activity (GO:0120548), molecular function activator activity (GO:0140677), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), protein-containing complex (GO:0032991), postsynaptic cytosol (GO:0099524)

Reactome top-level categories

Rollup of top-8 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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
intracellular anatomical structure	2
C-type glycerophospholipase activity	2
binding	2
regulation of blood pressure	1
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
Gq/11-coupled serotonin receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled serotonin receptor signaling pathway	1
lipid metabolic process	1
catabolic process	1
phosphorus metabolic process	1
intracellular signal transduction	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
metal ion binding	1
protein binding	1
cell adhesion molecule binding	1
molecular_function	1
molecular function regulator activity	1
phosphoric ester hydrolase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular_component	1
cytosol	1
postsynapse	1

Protein interactions and networks

STRING

1478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCB3	GNAQ	P50148	990
PLCB3	CHRM1	P11229	796
PLCB3	PYGM	P11217	792
PLCB3	FKBP2	P26885	784
PLCB3	AHNAK	Q09666	782
PLCB3	SF1	Q15637	774
PLCB3	COX8A	P10176	769
PLCB3	CAPN1	P07384	769
PLCB3	FTH1	P02794	767
PLCB3	ROM1	Q03395	767
PLCB3	MAP3K11	Q16584	767
PLCB3	FOSL1	P15407	766
PLCB3	SCGB1A1	P11684	765
PLCB3	MARK2	Q7KZI7	765
PLCB3	NHERF1	O14745	744

IntAct

64 interactions, top by confidence:

A	B	Type	Score
RAMAC	RNMT	psi-mi:“MI:0914”(association)	0.810
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
Gnaq	PLCB3	psi-mi:“MI:0407”(direct interaction)	0.750
PLCB3	Gnaq	psi-mi:“MI:0407”(direct interaction)	0.750
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
AP2S1	AP2A2	psi-mi:“MI:0914”(association)	0.640
NHERF1	PLCB3	psi-mi:“MI:0915”(physical association)	0.560
PARD3	PLCB3	psi-mi:“MI:0915”(physical association)	0.520
PARD6A	PLCB3	psi-mi:“MI:0915”(physical association)	0.520
PLCB3	PARD3	psi-mi:“MI:0915”(physical association)	0.520
PLCB3	PARD6A	psi-mi:“MI:0915”(physical association)	0.520
EZR	PLCB3	psi-mi:“MI:0915”(physical association)	0.400
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
NEDD1	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
SNTA1	GNAT3	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
	SDCBP	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
NHERF1	PODXL	psi-mi:“MI:0914”(association)	0.350
MAG	PLCB3	psi-mi:“MI:0914”(association)	0.350

BioGRID (115): PLCB3 (Affinity Capture-RNA), PLCB3 (Affinity Capture-RNA), SMYD3 (Co-fractionation), PLCB3 (Affinity Capture-MS), PLCB3 (Affinity Capture-MS), PLCB3 (Affinity Capture-MS), PLCB3 (Affinity Capture-MS), PLCB3 (Reconstituted Complex), PLCB3 (Affinity Capture-Western), PLCB3 (Proximity Label-MS), PLCB3 (Affinity Capture-MS), PLCB3 (Affinity Capture-MS), PLCB3 (Proximity Label-MS), PLCB3 (Proximity Label-MS), PLCB3 (Proximity Label-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FGR8, A0FGR9, A2AP18, A4IJ05, O08625, O08874, O15357, O75038, P51432, P70218, P70268, Q01970, Q12851, Q3TZZ7, Q3U7R1, Q4VX76, Q5DTI8, Q5FWL4, Q5M7N9, Q5R8Q5, Q5RAG2, Q5RCK6, Q5RJH2, Q61161, Q62807, Q63433, Q6DN12, Q6XYQ8, Q7ZWU7, Q812E4, Q86SS6, Q8K394, Q8TDW5, Q920M7, Q925C0, Q92918, Q99JE6, Q99N48, Q9BSJ8

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

12 interactions.

A	Effect	B	Mechanism
PLCB3	“up-regulates quantity”	“1D-myo-inositol 1,4,5-trisphosphate(6-)”	“chemical modification”
MAP3K8	“up-regulates activity”	PLCB3	phosphorylation
PRKCA	down-regulates	PLCB3	phosphorylation
PRKACA	down-regulates	PLCB3	phosphorylation
PRKG1	“down-regulates activity”	PLCB3	phosphorylation
PRKG2	“down-regulates activity”	PLCB3	phosphorylation
CAMK2B	unknown	PLCB3	phosphorylation
CAMK2G	unknown	PLCB3	phosphorylation
PLCB3	“up-regulates quantity”	superoxide
GNB/GNG	up-regulates	PLCB3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
EPH-Ephrin signaling	5	15.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	127
Likely benign	13
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1686865	NM_000932.5(PLCB3):c.2632G>T (p.Ala878Ser)	Likely pathogenic

SpliceAI

4522 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64251723:GGA:G	donor_gain	1.0000
11:64251724:GAG:G	donor_gain	1.0000
11:64251726:G:GG	donor_gain	1.0000
11:64251748:GGTA:G	donor_loss	1.0000
11:64251749:G:C	donor_loss	1.0000
11:64251750:T:G	donor_loss	1.0000
11:64254411:TCAG:T	acceptor_loss	1.0000
11:64254412:CAG:C	acceptor_loss	1.0000
11:64254413:A:AG	acceptor_gain	1.0000
11:64254413:AG:A	acceptor_gain	1.0000
11:64254413:AGG:A	acceptor_loss	1.0000
11:64254414:G:GG	acceptor_gain	1.0000
11:64254414:G:T	acceptor_loss	1.0000
11:64254414:GG:G	acceptor_gain	1.0000
11:64254414:GGA:G	acceptor_gain	1.0000
11:64254477:G:GT	donor_gain	1.0000
11:64254745:CA:C	acceptor_loss	1.0000
11:64254746:A:AG	acceptor_gain	1.0000
11:64254746:AG:A	acceptor_gain	1.0000
11:64254746:AGG:A	acceptor_loss	1.0000
11:64254747:G:GC	acceptor_gain	1.0000
11:64254747:GG:G	acceptor_gain	1.0000
11:64254747:GGA:G	acceptor_gain	1.0000
11:64255024:G:GT	donor_gain	1.0000
11:64255037:AG:A	donor_loss	1.0000
11:64255038:GGT:G	donor_loss	1.0000
11:64255039:G:C	donor_loss	1.0000
11:64255040:T:G	donor_loss	1.0000
11:64255312:GC:G	donor_gain	1.0000
11:64255314:G:GG	donor_gain	1.0000

AlphaMissense

8046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64251740:T:A	W31R	1.000
11:64251740:T:C	W31R	1.000
11:64256746:C:G	H332D	1.000
11:64256747:A:T	H332L	1.000
11:64256748:T:A	H332Q	1.000
11:64256748:T:G	H332Q	1.000
11:64256749:A:G	N333D	1.000
11:64256751:C:A	N333K	1.000
11:64256751:C:G	N333K	1.000
11:64256755:T:C	Y335H	1.000
11:64256759:T:C	L336P	1.000
11:64258540:C:G	C360W	1.000
11:64258544:G:A	E362K	1.000
11:64258545:A:T	E362V	1.000
11:64258546:G:C	E362D	1.000
11:64258546:G:T	E362D	1.000
11:64258548:T:A	L363Q	1.000
11:64258548:T:C	L363P	1.000
11:64258550:G:C	D364H	1.000
11:64258551:A:C	D364A	1.000
11:64258551:A:G	D364G	1.000
11:64258551:A:T	D364V	1.000
11:64258552:C:A	D364E	1.000
11:64258552:C:G	D364E	1.000
11:64258556:T:A	W366R	1.000
11:64258556:T:C	W366R	1.000
11:64258558:G:C	W366C	1.000
11:64258558:G:T	W366C	1.000
11:64258590:T:A	I377N	1.000
11:64258595:C:A	H379N	1.000

dbSNP variants (sampled 300 via entrez): RS1000087390 (11:64252073 G>A,C), RS1000208240 (11:64255888 A>G), RS1000250866 (11:64264482 C>G), RS1000288474 (11:64267667 A>G,T), RS1000390230 (11:64250016 G>A), RS1000517983 (11:64257811 T>C), RS1000548967 (11:64257359 A>G), RS1000748943 (11:64251256 G>A,T), RS1001031510 (11:64264013 C>A,T), RS1001119105 (11:64251767 G>C,T), RS1001241446 (11:64262705 T>C), RS1001278622 (11:64268976 T>C,G), RS1001498655 (11:64252681 G>C), RS1001503470 (11:64250438 G>A,T), RS1001551157 (11:64252526 C>G)

Disease associations

OMIM: gene MIM:600230 | disease phenotypes: MIM:618961

GenCC curated gene-disease

Disease	Classification	Inheritance
spondylometaphyseal dysplasia with corneal dystrophy	Limited	Unknown
spondylometaphyseal dysplasia	Limited	Autosomal recessive

Mondo (2): spondylometaphyseal dysplasia with corneal dystrophy (MONDO:0030074), spondylometaphyseal dysplasia (MONDO:0016763)

Orphanet (1): Spondylometaphyseal dysplasia-corneal dystrophy syndrome (Orphanet:589435)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000316	Hypertelorism
HP:0000463	Anteverted nares
HP:0000520	Proptosis
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0001156	Brachydactyly
HP:0001319	Neonatal hypotonia
HP:0001643	Patent ductus arteriosus
HP:0002643	Neonatal respiratory distress
HP:0003016	Metaphyseal widening
HP:0003026	Short long bone
HP:0003177	Squared iliac bones
HP:0003196	Short nose
HP:0003819	Death in childhood
HP:0004568	Beaking of vertebral bodies
HP:0004592	Thoracic platyspondyly
HP:0005280	Depressed nasal bridge
HP:0005787	Lumbar platyspondyly
HP:0007957	Corneal opacity
HP:0009826	Limb undergrowth
HP:0011344	Severe global developmental delay
HP:0030320	Increased intervertebral space
HP:0100670	Coarse metaphyseal trabecularization

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004611_180	High light scatter reticulocyte count	2.000000e-10
GCST004612_118	High light scatter reticulocyte percentage of red cells	1.000000e-09
GCST004785_38	Vitiligo	5.000000e-08
GCST007483_23	Waist-to-hip ratio adjusted for BMI (additive genetic model)	9.000000e-15
GCST007487_49	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-13
GCST007500_41	Waist-to-hip ratio adjusted for BMI (additive genetic model)	7.000000e-16
GCST007502_22	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1.000000e-15
GCST007516_26	Type 2 diabetes (adjusted for BMI)	2.000000e-06
GCST007518_21	Type 2 diabetes (adjusted for BMI)	2.000000e-07
GCST90002385_205	High light scatter reticulocyte count	6.000000e-14
GCST90002386_355	High light scatter reticulocyte percentage of red cells	9.000000e-13
GCST90002389_365	Lymphocyte percentage of white cells	4.000000e-10
GCST90002397_526	Mean spheric corpuscular volume	8.000000e-21
GCST90002397_527	Mean spheric corpuscular volume	2.000000e-09
GCST90002403_203	Red blood cell count	2.000000e-10
GCST90002405_283	Reticulocyte count	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5449 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

142 measured of 145 human assays (157 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
5-cyclopentylidene-2-sulfanylidene-1,3-thiazolidin-4-one	IC50	240 nM
4-[(E)-[3-(2-methylanilino)-4-oxo-1-naphthalenylidene]amino]sulfonylbenzoic acid	IC50	522 nM
(NZ)-N-[3-(4-hydroxyanilino)-4-keto-1-naphthylidene]thiophene-2-sulfonamide	IC50	656 nM
4-({(4Z)-1-oxo-4-[(phenylsulfonyl)imino]-1,4-dihydronaphthalen-2-yl}amino)benzoic acid	IC50	967 nM
3-(2-{(E)-[1-(4-chlorophenyl)-2,5-dioxoimidazolidin-4-ylidene]methyl}-1H-pyrrol-1-yl)benzoic acid	IC50	1230 nM
2,3,4,5-tetrahydroxy-6-benzo[7]annulenone	IC50	1230 nM
(2Z)-1,3-diketo-2-[(5-methyl-2-furyl)methylene]indane-5-carboxylic acid	IC50	1650 nM
(5Z)-5-[(E)-3-(2-furanyl)prop-2-enylidene]-3-(4-hydroxyphenyl)-2-sulfanylidene-4-thiazolidinone	IC50	1720 nM
1,6-dimethyl-3-propyl-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1770 nM
5-[(E)-3-(5-Nitro-furan-2-yl)-prop-2-en-(Z)-ylidene]-2-thioxo-thiazolidin-4-one	IC50	1920 nM
2-Methyl-8-morpholin-4-yl-5,6-dioxo-5,6-dihydro-quinoline-4-carboxylic acid methyl ester	IC50	3210 nM
MLS000334119	IC50	3440 nM
1,6-dimethyl-3-(2-pyridinyl)pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione	IC50	10200 nM
4-[(5Z)-5-[(E)-3-(2-furanyl)prop-2-enylidene]-4-oxo-2-sulfanylidene-3-thiazolidinyl]butanoic acid	IC50	19300 nM
1-[[(E)-(2,3-dihydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]amino]-3-(3-pyridyl)thiourea	IC50	19500 nM
cid_360404	IC50	40800 nM
3-[(2Z)-2-(3-formyl-4-oxo-1-cyclohexa-2,5-dienylidene)hydrazinyl]benzoic acid	IC50	42500 nM
SMR003100911	IC50	45100 nM
MLS004342426	IC50	47200 nM
SMR003287627	IC50	55400 nM
cid_60159071	IC50	61900 nM
cid_616832	IC50	102000 nM
cid_340219	IC50	122000 nM
SMR000114997	IC50	122000 nM
cid_240739	IC50	122000 nM
cid_46742345	IC50	122000 nM
3-(2-methoxyphenyl)-2-[(2-oxolanylmethylamino)methyl]-4-quinazolinone	IC50	122000 nM
N-(4-benzamido-3-methylphenyl)-3-ethoxybenzamide	IC50	122000 nM
N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(3-methyl-2-methylimino-4-oxo-5-thiazolidinyl)acetamide	IC50	122000 nM
2-[1,3-bis(oxidanylidene)isoindol-2-yl]-N-[4-[(2,6-dimethoxypyrimidin-4-yl)sulfamoyl]phenyl]ethanamide	IC50	122000 nM
cid_5484353	IC50	122000 nM
2-[[3-(4-methylphenyl)adamantane-1-carbonyl]amino]acetic acid	IC50	122000 nM
3-(2,4-dichlorophenyl)quinazoline-2,4(1H,3H)-dione	IC50	122000 nM
N-[2-(hydroxymethyl)-2,3-dihydro-1H-benzo[f]chromen-1-yl]-N-methylbenzenecarboxamide	IC50	122000 nM
[5-(6-aminopurin-9-yl)-3,4-dihydroxy-2-oxolanyl]methyl hydrogen phosphate;triethylammonium	IC50	122000 nM
N-[4-(5-tert-butyltriazol-1-yl)phenyl]-3-methoxybenzamide	IC50	122000 nM
SMR001399237	IC50	122000 nM
methyl 2-[(2S,4aR,12aR)-8-[(3-fluorophenyl)carbonylamino]-5-methyl-6-oxidanylidene-2,3,4,4a,12,12a-hexahydropyrano[2,3-c][1,5]benzoxazocin-2-yl]ethanoate	IC50	122000 nM
N-(3-fluorophenyl)-2-(phenylmethylthio)acetamide	IC50	122000 nM
cid_5100198	IC50	122000 nM
2-[2-[methyl(phenyl)amino]-2-oxidanylidene-ethoxy]-N-(2-phenoxyethyl)benzamide	IC50	122000 nM
SMR000151524	IC50	122000 nM
N-[2,4-bis(fluoranyl)phenyl]-5-(2-methoxyphenyl)-1,2-oxazole-3-carboxamide	IC50	122000 nM
SMR000475961	IC50	122000 nM
ethyl 2-[[4-(2-methylphenyl)-5-[(2-oxidanylidene-1,3-benzothiazol-3-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]ethanoate	IC50	122000 nM
MLS001157843	IC50	122000 nM
3-(4-methylphenyl)sulfonyl-N-(4-pyridin-4-yl-2-thiazolyl)propanamide	IC50	122000 nM
3-(2-morpholin-4-ylethyl)-5H-pyrimido[5,4-b]indol-4-one	IC50	122000 nM
SMR000125727	IC50	122000 nM
MLS000325723	IC50	122000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	4
bisphenol A	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects expression, affects cotreatment	1
dicrotophos	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	affects expression, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	decreases reaction, increases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3215200	Binding	PubChem BioAssay. Fluorescence-based biochemical high throughput dose response assay to identify inhibitors of phospholipase C isozymes (PLC-B3). (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2B5	Abcam HeLa PLCB3 KO	Cancer cell line	Female
CVCL_B7YU	Abcam Raji PLCB3 KO	Cancer cell line	Male
CVCL_B9ZK	Abcam THP-1 PLCB3 KO	Cancer cell line	Male
CVCL_C7B9	Abcam PC-3 PLCB3 KO	Cancer cell line	Male
CVCL_E0L6	Ubigene HeLa PLCB3 KO	Cancer cell line	Female
CVCL_TE22	HAP1 PLCB3 (-) 1	Cancer cell line	Male
CVCL_TE23	HAP1 PLCB3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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