PLCB1

Summary

PLCB1 (phospholipase C beta 1, HGNC:15917) is a protein-coding gene on chromosome 20p12.3, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (Q9NQ66). Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors.

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23236 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 52
• Clinical variants (ClinVar): 1,281 total — 22 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_015192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15917
Approved symbol	PLCB1
Name	phospholipase C beta 1
Location	20p12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0581, PLC-I, PLC154
Ensembl gene	ENSG00000182621
Ensembl biotype	protein_coding
OMIM	607120
Entrez	23236

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 16 protein_coding, 9 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000338037, ENST00000378637, ENST00000378641, ENST00000404098, ENST00000437439, ENST00000439627, ENST00000475958, ENST00000487210, ENST00000494924, ENST00000625874, ENST00000626114, ENST00000626161, ENST00000626966, ENST00000628239, ENST00000628900, ENST00000629992, ENST00000630495, ENST00000630757, ENST00000635830, ENST00000635850, ENST00000635929, ENST00000636319, ENST00000636711, ENST00000636784, ENST00000636825, ENST00000637000, ENST00000637204, ENST00000637254, ENST00000637273, ENST00000637422, ENST00000637919, ENST00000637935

RefSeq mRNA: 2 — MANE Select: NM_015192 NM_015192, NM_182734

CCDS: CCDS13102, CCDS13103

Canonical transcript exons

ENST00000338037 — 32 exons

Exon	Start	End
ENSE00001294794	8371382	8371450
ENSE00001300522	8789518	8789575
ENSE00001309600	8150294	8150371
ENSE00001316999	8628294	8628431
ENSE00001321871	8788633	8788722
ENSE00001325975	8790175	8790261
ENSE00001606688	8716264	8716348
ENSE00001620588	8646102	8646181
ENSE00001633651	8708670	8708752
ENSE00001668571	8657184	8657284
ENSE00001685494	8649374	8649449
ENSE00001692458	8684932	8685078
ENSE00001695898	8647900	8647953
ENSE00001749276	8658538	8658704
ENSE00001788327	8697626	8697783
ENSE00003463769	8757046	8757178
ENSE00003469503	8722354	8722421
ENSE00003533643	8741464	8741573
ENSE00003536094	8765139	8765358
ENSE00003594414	8760407	8760460
ENSE00003595461	8737028	8737192
ENSE00003605565	8717671	8717848
ENSE00003607815	8733238	8733392
ENSE00003623211	8729050	8729174
ENSE00003624118	8788449	8788525
ENSE00003641500	8739261	8739360
ENSE00003658565	8724656	8724752
ENSE00003665939	8881622	8884900
ENSE00003673679	8740344	8740448
ENSE00003680048	8774539	8774719
ENSE00003681942	8727309	8727393
ENSE00003769242	8132266	8132750

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2798 / max 614.1915, expressed in 1292 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183424	15.3325	1273
183425	1.8662	627
183437	0.0475	16
183431	0.0335	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.11	gold quality
superior frontal gyrus	UBERON:0002661	98.08	gold quality
middle temporal gyrus	UBERON:0002771	98.00	gold quality
primary visual cortex	UBERON:0002436	97.93	gold quality
postcentral gyrus	UBERON:0002581	97.93	gold quality
parietal lobe	UBERON:0001872	97.70	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.55	gold quality
occipital lobe	UBERON:0002021	97.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.11	gold quality
frontal pole	UBERON:0002795	97.08	gold quality
entorhinal cortex	UBERON:0002728	96.91	gold quality
parotid gland	UBERON:0001831	96.57	gold quality
CA1 field of hippocampus	UBERON:0003881	96.36	gold quality
orbitofrontal cortex	UBERON:0004167	96.14	gold quality
sural nerve	UBERON:0015488	95.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.17	gold quality
prefrontal cortex	UBERON:0000451	95.11	gold quality
cauda epididymis	UBERON:0004360	94.84	gold quality
cranial nerve II	UBERON:0000941	94.73	gold quality
putamen	UBERON:0001874	94.44	gold quality
frontal cortex	UBERON:0001870	94.35	gold quality
lateral globus pallidus	UBERON:0002476	94.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.35	gold quality
cerebral cortex	UBERON:0000956	94.23	gold quality
caudate nucleus	UBERON:0001873	94.18	gold quality
neocortex	UBERON:0001950	93.95	gold quality
ganglionic eminence	UBERON:0004023	93.78	gold quality
telencephalon	UBERON:0001893	93.70	gold quality
parietal pleura	UBERON:0002400	93.09	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	5477.90
E-GEOD-131882	yes	3258.63
E-CURD-119	yes	2987.47
E-MTAB-11268	yes	2666.44
E-HCAD-25	yes	74.82
E-MTAB-10287	yes	50.28
E-ANND-3	yes	10.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, PAX6

miRNA regulators (miRDB)

255 targeting PLCB1, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-34C-5P	99.97	70.45	1577

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• detailed analysis of the human PLC beta1 gene showing the existence of alternative splicing; complete determination of the exon/intron structure of the gene spanning 250 kb of DNA (PMID:12213492)
• PLC beta 3 and PLC beta 1 bind to calmodulin (PMID:12821674)
• The myelodysplastic syndrome patients, bearing the deletion, rapidly evolved to acute myeloid leukemia. (PMID:15085153)
• This review summarizes current knowledge about nuclear PI-PLC-beta 1, its localization, activity changes during cell cycle phases, and possible involvement in the progression of myelodisplastic syndrome to acute myeloid leukemia. (PMID:16136505)
• alternative pathway operates in the absence of Lck-dependent tyrosine-phosphorylation events and was initiated by the T cell receptor-dependent activation of raft-enriched heterotrimeric Galpha11 proteins (PMID:16860758)
• These results support the model that activation of selected PLC isoforms at the cleavage furrow controls progression of cytokinesis through regulation of PIP2 levels (PMID:17041247)
• New data in this review hints at the fact that the imbalance of nuclear versus cytoplasmic phosphatidylinositol-phospholipase C beta 1 signaling could affect the cell cycle progression of hematopoietic cells. (PMID:17335878)
• These results demonstrate that two waves of nuclear PI-PLCbeta(1b) activity occur in serum-stimulated cells during G(1) phase of the cell cycle and that the later increase in the PLC activity is equally important for the progression into the S phase. (PMID:17363325)
• PC-PLC and ROS were involved in chicken blastodisc differentiation to vascular endothelial cells. PC-PLC was an important factor in the blastodisc cell survival and differentiation, and it might perform its function associated with ROS. (PMID:17393430)
• Spontaneous calcium oscillations and nuclear translocation of PLC-beta1 may reflect some degree of oocyte maturity. (PMID:17620288)
• PC-PLC activation through CCR5 is specifically induced by gp120, since triggering CCR5 through its natural ligand CCL4 (MIP-1beta) does not affect PC-PLC cellular distribution and enzymatic activity, as well as CCL2 secretion (PMID:18203956)
• Ins(1,4,5)P(3) and IP(3)-receptor (type 2) regulate PLCbeta1 and thereby maintain levels of Ins(1,4,5)P(3), which implies some functional significance for Ins(1,4,5)P(3) in the heart (PMID:18692062)
• PLCb1 localization is regulated by its own substrate, phosphatidylinositol (4,5)-bisphosphate. (PMID:18957514)
• The association between the presence of phosphoinositide-phospholipase C beta1 (PI-PLCbeta1) mono-allelic deletion with the clinical outcome of myelodysplastic syndromes (MDS) patients was evaluated. (PMID:19114693)
• An extracellular PI-PLC enzyme activity that may be acutely involved in the regulation of PtdIns levels in lung surfactant, was identified. (PMID:19491339)
• Data show that PI(3,4,5)P3 potentiates Ca(2+)-stimulated phospholipase C-beta activitiy. (PMID:19519170)
• Dilated atria from human and mouse showed heightened expression of PLCbeta1b. (PMID:19729020)
• These findings suggest that PLC/CAMK IV-NF-kappaB is involved in RAGE mediated signaling pathway in human endothelial cells. (PMID:20171262)
• data confirm that phospholipase C beta 1 transcript levels are decreased in the dorsolateral prefrontal cortex from subjects with schizophrenia. However, the changes in levels of mRNA do not translate into a change at the level of protein. (PMID:21091263)
• These studies suggest that Protein kinase C phosphorylation regulates the level of PLCB1 cytosolic and nuclear activity by regulating its cellular compartmentalization. (PMID:21338571)
• For the first time it is shown that SHP-2 and PLCbeta1 are present as a preformed complex. Complex PLCbeta1 is tyr-phosphorylated basally. Ang II increased SHP-2-PLCbeta1 complexes and caused complex associated PLCbeta1 tyr-phosphorylation to decline. (PMID:21663700)
• PI-PLCbeta1 gene amplification seems to be correlated to clinicopathological parameters. (PMID:22076473)
• Alpha-synuclein protects the integrity of PLCbeta1 and its ability to be activated by Galpha q, which may in turn impact calcium signaling. (PMID:22286107)
• PLCbeta1 expression is a key player in myoblast differentiation, functioning as a positive regulator in the correction of delayed differentiation of skeletal muscle in myotonic dystrophy myoblasts (PMID:22459146)
• existence of a susceptibility locus on the short arm of chromosome 20 moved us to analyse PLCB1, the gene codifying for PI-PLC beta1 enzyme, which maps on 20p12 (PMID:22507702)
• case report - homozygous deletion associated with malignant migrating partial seizures in infancy (PMID:22690784)
• Data show a novel role of phospholipase Cbeta1 (PLCbeta1) in gene regulation through translin-associated factor X (TRAX) association. (PMID:22889834)
• PLCbeta1 is enriched at the plasma membrane. (PMID:23006664)
• Nuclear signaling elicited by phospholipase C beta1 plays an important role in the control of the balance between cell cycle progression and apoptosis in myelodysplastic syndrome cells. (Review) (PMID:23058275)
• a concerted gp120-mediated signaling involving both PC- and PI-specific phospholipase C beta1 is required for the expression of CCL2 in macrophages (PMID:23555755)
• PLCbeta1 positively targets cyclin D3, likely through a PKCalpha mediatedpathway, and that, as a downstream effect of its activity, K562 cells undergo to an accumulation in the S phase of the cell cycle, leading to a decrease of cell proliferation. (PMID:23656785)
• A peptide that mimics part of the alpha-synuclein binding site to PLCbeta prevents aggregation. PLCbeta1 can reduce cell damage under oxidative stress and offers a potential site that might be exploited to prevent alpha-synuclein aggregation. (PMID:23659438)
• Cholesterol regulates HERG K+ channel activation by increasing phospholipase C beta1 expression (PMID:23793622)
• Interaction between PLCbeta1 and TRAX affect the function of TRAX as part of the machinery involved in RNA interference. [review] (PMID:23916604)
• PLCbeta1-linked signaling pathways may be involved in the neural system in schizophrenia. [review] (PMID:24035496)
• PLC-beta1 and DAGL-alpha are detected in discrete brain regions, with a marked predominance of pyramidal morphologies of positive cortical cells.[review] (PMID:24076015)
• nuclear PI-PLCb1 signalling is involved in diseases showing an altered myogenic differentiation and affecting the hematopoietic system.[review] (PMID:24296032)
• Novel variations in PLCB1 do not allow prediction of functional phenotypes that might explain, at least in part, the symptoms of malignant migrating partial seizures of infancy (MMPSI). (PMID:24315024)
• The selectivity of PLCbeta toward certain genes lies in the rate at which the RNA is hydrolyzed by C3PO. (PMID:24338081)
• Phospholipase C-beta1 and beta4 contribute to non-genetic cell-to-cell variability in histamine-induced calcium signals in HeLa cells. (PMID:24475116)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	plcb1	ENSDARG00000109726
danio_rerio		ENSDARG00000116804
mus_musculus	Plcb1	ENSMUSG00000051177
rattus_norvegicus	Plcb1	ENSRNOG00000004810
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), PLCB2 (ENSG00000137841), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCB3 (ENSG00000149782), PLCL2 (ENSG00000154822), PLCD3 (ENSG00000161714), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 — Q9NQ66 (reviewed: Q9NQ66)

Alternative names: PLC-154, Phosphoinositide phospholipase C-beta-1, Phospholipase C-I, Phospholipase C-beta-1

All UniProt accessions (17): Q9NQ66, A0A0D9SF51, A0A0D9SFA6, A0A0D9SFE7, A0A0D9SFJ4, A0A0D9SG17, A0A0D9SGI7, A0A1B0GTC7, A0A1B0GVC1, A0A1B0GVT0, A0A1B0GW45, A0A1B0GW62, A0A1B0GWB6, B1AK73, H0YCJ2, Q8IV91, Q8IV92

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors. Regulates the function of the endothelial barrier.

Subunit / interactions. Interacts with DGKQ.

Subcellular location. Nucleus membrane. Cytoplasm.

Post-translational modifications. Palmitoylated. Palmitoylation at Cys-17 by ZDHHC21 regulates the signaling activity of PLCB1 and the function of the endothelial barrier. Palmitoylation by ZDHHC21 is stimulated by inflammation.

Disease relevance. Developmental and epileptic encephalopathy 12 (DEE12) [MIM:613722] A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The receptor-mediated activation of PLC-beta-1 is mediated by two G-protein alpha subunits, alpha-Q and alpha-11.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQ66-1	A	yes
Q9NQ66-2	B

RefSeq proteins (2): NP_056007, NP_877398 (=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
IPR028400	PLC-beta1_EF	Domain
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: 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 (43 total): sequence conflict 12, modified residue 10, compositionally biased region 6, region of interest 5, domain 3, active site 2, sequence variant 2, chain 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ66-F1	84.55	0.67

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): 331; 378

Post-translational modifications (11): 236, 417, 509, 511, 582, 887, 978, 987, 1199, 1200, 17

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: 714 (showing top): GOBP_MEMORY, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_SINGLE_FERTILIZATION, AGGAAGC_MIR5163P, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BIOCARTA_FMLP_PATHWAY, GOBP_COGNITION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_MYELOID_LEUKOCYTE_MIGRATION

GO Biological Process (48): G2/M transition of mitotic cell cycle (GO:0000086), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway (GO:0007207), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), glutamate receptor signaling pathway (GO:0007215), learning (GO:0007612), memory (GO:0007613), regulation of G protein-coupled receptor signaling pathway (GO:0008277), positive regulation of glycoprotein biosynthetic process (GO:0010560), cerebral cortex development (GO:0021987), phosphatidylinositol catabolic process (GO:0031161), positive regulation of insulin secretion (GO:0032024), positive regulation of interleukin-12 production (GO:0032735), inositol trisphosphate metabolic process (GO:0032957), interleukin-12-mediated signaling pathway (GO:0035722), interleukin-15-mediated signaling pathway (GO:0035723), positive regulation of embryonic development (GO:0040019), fat cell differentiation (GO:0045444), positive regulation of myoblast differentiation (GO:0045663), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of JNK cascade (GO:0046330), phosphatidylinositol metabolic process (GO:0046488), insulin-like growth factor receptor signaling pathway (GO:0048009), phosphatidylinositol-mediated signaling (GO:0048015), positive regulation of developmental growth (GO:0048639), release of sequestered calcium ion into cytosol (GO:0051209), activation of meiosis involved in egg activation (GO:0060466), interleukin-1-mediated signaling pathway (GO:0070498), regulation of fertilization (GO:0080154), postsynaptic modulation of chemical synaptic transmission (GO:0099170), regulation of retrograde trans-synaptic signaling by endocanabinoid (GO:0099178), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), cellular response to fluoride (GO:1902618), regulation of establishment of endothelial barrier (GO:1903140), cellular response to vasopressin (GO:1904117), cellular response to ionomycin (GO:1904637), cellular response to glyceraldehyde (GO:1905631), ligand-gated ion channel signaling pathway (GO:1990806)

GO Molecular Function (14): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), C-type glycerophospholipase activity (GO:0004629), GTPase activator activity (GO:0005096), calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), lamin binding (GO:0005521), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), enzyme binding (GO:0019899), identical protein binding (GO:0042802), 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 (12): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), postsynaptic cytosol (GO:0099524), membrane (GO:0016020)

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
protein binding	4
cellular anatomical structure	4
G protein-coupled receptor signaling pathway	2
learning or memory	2
cytokine-mediated signaling pathway	2
C-type glycerophospholipase activity	2
synapse	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
cell surface receptor signaling pathway	1
glutamate receptor activity	1
regulation of signal transduction	1
glycoprotein biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
regulation of glycoprotein biosynthetic process	1
positive regulation of glycoprotein metabolic process	1
pallium development	1
anatomical structure development	1
catabolic process	1
phosphatidylinositol metabolic process	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
positive regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
inositol phosphate metabolic process	1

Protein interactions and networks

STRING

2000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCB1	GNAQ	P50148	985
PLCB1	NHERF2	Q15599	762
PLCB1	SLC25A22	Q9H936	752
PLCB1	TRPM7	Q96QT4	714
PLCB1	PCDH19	Q8TAB3	704
PLCB1	ADCY5	O95622	687
PLCB1	PNKP	Q96T60	668
PLCB1	ARX	Q96QS3	668
PLCB1	PCDH10	Q9P2E7	664
PLCB1	GNG2	P59768	663
PLCB1	EEF2K	O00418	653
PLCB1	GNB1	P04697	650
PLCB1	RGS4	P49798	643
PLCB1	TSNAX	Q99598	641
PLCB1	ARHGEF9	O43307	640

IntAct

160 interactions, top by confidence:

A	B	Type	Score
CTBP2	PLCB1	psi-mi:“MI:0915”(physical association)	0.560
PLCB1	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
CTBP1	PLCB1	psi-mi:“MI:0915”(physical association)	0.560
CEP76	PLCB1	psi-mi:“MI:0915”(physical association)	0.560
PLCB1	CTBP2	psi-mi:“MI:0915”(physical association)	0.560
TFCP2	PLCB1	psi-mi:“MI:0915”(physical association)	0.560
PLCB1	CTBP1	psi-mi:“MI:0915”(physical association)	0.560
PLCB1	CEP76	psi-mi:“MI:0915”(physical association)	0.560
BTN2A1	POTEF	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
PLCB1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
PDZRN3	PLCB1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
PLCB1	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (75): PLCB1 (Two-hybrid), PLCB1 (Two-hybrid), PLCB1 (Two-hybrid), CEP76 (Two-hybrid), PLCB1 (Affinity Capture-MS), PLCB1 (Affinity Capture-MS), PLCB1 (Affinity Capture-MS), GNAQ (Reconstituted Complex), GNAQ (FRET), GNAQ (Affinity Capture-Western), PLCB1 (Affinity Capture-MS), PLCB1 (Affinity Capture-MS), PLCB1 (Affinity Capture-MS), PLCB1 (Proximity Label-MS), PLCB1 (Proximity Label-MS)

ESM2 similar proteins: A0A075QQ08, A0A0P0V4R0, A0A1D8EJF9, A0A1U8F5V2, A0A1U8GR65, A0A2J6L8Y7, A0A3Q7FGP1, A0A3Q7I7R4, A0A445AGS0, A2X0Q3, A7KWF8, C6ZJZ3, C7SG33, D3UW26, K0P2S0, M1J8U6, M1JJT8, O23252, O60573, O77210, O81481, O81482, P0DXI0, P0DXI5, P10687, P10894, P29557, P48599, P48600, Q03389, Q0GRC4, Q3UTA9, Q4QXS7, Q4VQY1, Q4VQY3, Q5ZLV4, Q66UV4, Q66WU1, Q6YXZ7, Q8BMB3

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

17 interactions.

A	Effect	B	Mechanism
PLCB1	up-regulates	GNA11	binding
DVL1	“up-regulates activity”	PLCB1
DVL2	“up-regulates activity”	PLCB1
DVL3	“up-regulates activity”	PLCB1
GNAS	“up-regulates activity”	PLCB1	binding
GNA11	“up-regulates activity”	PLCB1	binding
GNAQ	up-regulates	PLCB1	binding
GNB1	down-regulates	PLCB1	binding
PRKCA	unknown	PLCB1	phosphorylation
MAPK1	“up-regulates activity”	PLCB1	phosphorylation
MAPK3	“up-regulates activity”	PLCB1	phosphorylation
PLCB1	“up-regulates quantity”	1,2-diacyl-sn-glycerol	“chemical modification”
PLCB1	“up-regulates quantity”	“1D-myo-inositol 1,4,5-trisphosphate”	“chemical modification”
Gbeta	“up-regulates activity”	PLCB1	phosphorylation
ERK1/2	“up-regulates activity”	PLCB1	phosphorylation
GNA14	“up-regulates activity”	PLCB1	binding
GNA15	“up-regulates activity”	PLCB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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	8	59.3×	5e-11
Unblocking of NMDA receptors, glutamate binding and activation	5	35.3×	1e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	35.3×	1e-05
Assembly and cell surface presentation of NMDA receptors	10	33.0×	5e-11
Dopamine Neurotransmitter Release Cycle	5	32.2×	2e-05
Long-term potentiation	5	30.9×	2e-05
Neurexins and neuroligins	11	28.1×	4e-11
Protein-protein interactions at synapses	7	24.1×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	55.3×	8e-13
protein localization to synapse	6	43.8×	9e-07
receptor clustering	7	41.6×	9e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	28.3×	9e-06
Ras protein signal transduction	5	9.8×	6e-03
cell-cell adhesion	10	9.7×	1e-05
protein-containing complex assembly	8	8.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1281 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	14
Uncertain significance	499
Likely benign	525
Benign	118

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070278	NC_000020.10:g.(?8608931)(8639361_?)del	Pathogenic
1435065	NM_015192.4(PLCB1):c.2666del (p.Lys889fs)	Pathogenic
1451701	NM_015192.4(PLCB1):c.967del (p.Ser323fs)	Pathogenic
1456484	NC_000020.10:g.(?8639165)(8698515_?)del	Pathogenic
2020515	NM_015192.4(PLCB1):c.1678dup (p.Arg561fs)	Pathogenic
2097870	NM_015192.4(PLCB1):c.2155del (p.Gln719fs)	Pathogenic
2102622	NM_015192.4(PLCB1):c.1087del (p.Asp363fs)	Pathogenic
2426093	NC_000020.10:g.(?8696891)(8698515_?)del	Pathogenic
2907828	NM_015192.4(PLCB1):c.3094C>T (p.Arg1032Ter)	Pathogenic
30644	NC_000020.10:g.(8094049_8094072)_(8580261_8580284)del	Pathogenic
3248294	NC_000020.10:g.(?8113299)(8352117_?)del	Pathogenic
3660331	NM_015192.4(PLCB1):c.569del (p.Glu190fs)	Pathogenic
3903186	NM_015192.4(PLCB1):c.550C>T (p.Arg184Ter)	Pathogenic
4279159	GRCh37/hg19 20p12.3(chr20:8097725-8586513)x1	Pathogenic
433139	NM_015192.4(PLCB1):c.3382C>T (p.His1128Tyr)	Pathogenic
4733406	NM_015192.4(PLCB1):c.3357del (p.Lys1119fs)	Pathogenic
620493	NM_015192.4(PLCB1):c.1332T>A (p.Tyr444Ter)	Pathogenic
648249	NM_015192.4(PLCB1):c.1612G>T (p.Glu538Ter)	Pathogenic
685161	GRCh37/hg19 20p12.3(chr20:8512966-8792352)x1	Pathogenic
685388	GRCh37/hg19 20p12.3(chr20:8089954-8572965)x1	Pathogenic
687733	GRCh37/hg19 20p12.3(chr20:8843844-8880111)x1	Pathogenic
831489	NC_000020.10:g.(?8113279)(8352117_?)del	Pathogenic
1481396	NM_015192.4(PLCB1):c.465-2A>C	Likely pathogenic
1486443	NM_015192.4(PLCB1):c.2208+1G>A	Likely pathogenic
1507516	NM_015192.4(PLCB1):c.1168-1G>A	Likely pathogenic
1907709	NM_015192.4(PLCB1):c.464+1G>A	Likely pathogenic
2016582	NM_015192.4(PLCB1):c.178-2A>G	Likely pathogenic
2086527	NM_015192.4(PLCB1):c.1763+2T>C	Likely pathogenic
2115179	NM_015192.4(PLCB1):c.2656+1G>T	Likely pathogenic
2798897	NM_015192.4(PLCB1):c.862+1G>A	Likely pathogenic

SpliceAI

3143 predictions. Top by Δscore:

Variant	Effect	Δscore
20:8132746:ATGAT:A	donor_gain	1.0000
20:8132747:TGAT:T	donor_gain	1.0000
20:8132748:GAT:G	donor_gain	1.0000
20:8132748:GATG:G	donor_gain	1.0000
20:8132749:AT:A	donor_gain	1.0000
20:8132750:TGTA:T	donor_loss	1.0000
20:8132751:G:GG	donor_gain	1.0000
20:8150287:T:G	acceptor_gain	1.0000
20:8150288:TTCTA:T	acceptor_loss	1.0000
20:8150289:TCTA:T	acceptor_loss	1.0000
20:8150290:CTAG:C	acceptor_loss	1.0000
20:8150291:TA:T	acceptor_loss	1.0000
20:8150292:A:AG	acceptor_gain	1.0000
20:8150293:G:A	acceptor_loss	1.0000
20:8150293:G:GG	acceptor_gain	1.0000
20:8150371:GGTAA:G	donor_loss	1.0000
20:8150372:G:A	donor_loss	1.0000
20:8150373:T:A	donor_loss	1.0000
20:8280935:G:GT	donor_gain	1.0000
20:8406280:A:AG	acceptor_gain	1.0000
20:8406281:G:GG	acceptor_gain	1.0000
20:8132752:TAA:T	donor_loss	0.9900
20:8150285:C:G	acceptor_gain	0.9900
20:8150286:A:AG	acceptor_gain	0.9900
20:8371376:TTCCA:T	acceptor_loss	0.9900
20:8371377:TCCA:T	acceptor_loss	0.9900
20:8371379:CA:C	acceptor_loss	0.9900
20:8371380:A:AG	acceptor_gain	0.9900
20:8371380:A:G	acceptor_loss	0.9900
20:8371381:G:GA	acceptor_loss	0.9900

AlphaMissense

8070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:8685042:T:G	Y325D	1.000
20:8685055:C:T	S329F	1.000
20:8685060:C:G	H331D	1.000
20:8685061:A:T	H331L	1.000
20:8685062:C:A	H331Q	1.000
20:8685062:C:G	H331Q	1.000
20:8685063:A:G	N332D	1.000
20:8685064:A:T	N332I	1.000
20:8685065:C:A	N332K	1.000
20:8685065:C:G	N332K	1.000
20:8685069:T:C	Y334H	1.000
20:8685069:T:G	Y334D	1.000
20:8685073:T:A	L335H	1.000
20:8685073:T:C	L335P	1.000
20:8697633:A:C	Q339H	1.000
20:8697633:A:T	Q339H	1.000
20:8697691:T:C	C359R	1.000
20:8697693:T:G	C359W	1.000
20:8697697:G:A	E361K	1.000
20:8697698:A:T	E361V	1.000
20:8697699:G:C	E361D	1.000
20:8697699:G:T	E361D	1.000
20:8697701:T:A	L362Q	1.000
20:8697701:T:C	L362P	1.000
20:8697703:G:C	D363H	1.000
20:8697704:A:C	D363A	1.000
20:8697704:A:G	D363G	1.000
20:8697704:A:T	D363V	1.000
20:8697705:C:A	D363E	1.000
20:8697705:C:G	D363E	1.000

dbSNP variants (sampled 300 via entrez): RS1000012107 (20:8884382 A>T), RS1000012411 (20:8190480 G>A), RS1000014339 (20:8675639 C>A), RS1000018930 (20:8829535 T>C), RS1000020286 (20:8547162 C>A), RS1000024124 (20:8732261 G>A), RS1000029422 (20:8698192 AAC>A), RS1000034500 (20:8589016 C>T), RS1000042109 (20:8583280 T>G), RS1000050171 (20:8829380 C>G), RS1000052063 (20:8578369 C>T), RS1000054497 (20:8154929 C>A), RS1000059088 (20:8197995 C>A,T), RS1000059259 (20:8498254 C>A,T), RS1000061301 (20:8347672 A>G)

Disease associations

OMIM: gene MIM:607120 | disease phenotypes: MIM:613722, MIM:117100, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 12	Strong	Autosomal recessive
malignant migrating partial seizures of infancy	Supportive	Autosomal dominant
infantile spasms	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AR

Mondo (5): developmental and epileptic encephalopathy, 12 (MONDO:0013389), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), developmental and epileptic encephalopathy, 1 (MONDO:0010632), malignant migrating partial seizures of infancy (MONDO:0017385), infantile spasms (MONDO:0018097)

Orphanet (1): Self-limited epilepsy with centrotemporal spikes (Orphanet:1945)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000505	Visual impairment
HP:0000707	Abnormality of the nervous system
HP:0000826	Precocious puberty
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001273	Abnormal corpus callosum morphology
HP:0001276	Hypertonia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002376	Developmental regression
HP:0002384	Focal impaired awareness seizure
HP:0002521	Hypsarrhythmia
HP:0002540	Inability to walk
HP:0002650	Scoliosis
HP:0003593	Infantile onset
HP:0004302	Functional motor deficit
HP:0006813	Focal hemiclonic seizure
HP:0007334	Bilateral tonic-clonic seizure with focal onset
HP:0007359	Focal-onset seizure
HP:0008936	Axial hypotonia
HP:0010821	Focal emotional seizure with laughing
HP:0010841	Multifocal epileptiform discharges
HP:0011097	Epileptic spasm
HP:0011121	Abnormal skin morphology
HP:0012448	Delayed myelination

GWAS associations

52 associations (top):

Study	Trait	p-value
GCST000477_35	Cognitive performance	2.000000e-06
GCST000579_42	Cognitive performance	7.000000e-06
GCST001558_2	Response to irinotecan in non-small-cell lung cancer	6.000000e-06
GCST001792_4	Colorectal cancer	7.000000e-09
GCST001792_6	Colorectal cancer	2.000000e-07
GCST002367_16	Social communication problems	8.000000e-08
GCST002974_1	Suicide ideation score in major depressive disorder	8.000000e-07
GCST003140_3	Chronic kidney disease	6.000000e-06
GCST003518_23	Daytime sleep phenotypes	6.000000e-07
GCST003675_3	Obstructive sleep apnea trait (average respiratory event duration)	2.000000e-07
GCST004280_87	Diastolic blood pressure	1.000000e-11
GCST004603_280	Platelet count	4.000000e-11
GCST004607_31	Plateletcrit	6.000000e-25
GCST004610_97	White blood cell count	3.000000e-11
GCST004616_151	Platelet distribution width	3.000000e-12
GCST004625_220	Monocyte count	1.000000e-14
GCST004627_106	Lymphocyte count	4.000000e-12
GCST007927_43	Medication use (beta blocking agents)	4.000000e-15
GCST007928_90	Medication use (diuretics)	6.000000e-21
GCST007929_33	Medication use (calcium channel blockers)	2.000000e-11
GCST007930_97	Medication use (agents acting on the renin-angiotensin system)	4.000000e-20
GCST008058_210	Estimated glomerular filtration rate	1.000000e-12
GCST008059_175	Estimated glomerular filtration rate	4.000000e-13
GCST008747_141	Estimated glomerular filtration rate	2.000000e-08
GCST008829_6	Neuritic plaque	5.000000e-06
GCST009028_5	Adverse response to drug	4.000000e-07
GCST009218_35	Lateral ventricle temporal horn volume	9.000000e-06
GCST009391_1653	Metabolite levels	3.000000e-06
GCST012047_21	Fasting glucose	4.000000e-07
GCST012490_358	Femur bone mineral density x serum urate levels interaction	2.000000e-12

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0005427	social communication impairment
EFO:0007619	suicide ideation measurement
EFO:0007828	daytime rest measurement
EFO:0007817	sleep apnea measurement
EFO:0006336	diastolic blood pressure
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0006798	neuritic plaque measurement
EFO:0009658	adverse effect
EFO:0010469	carnitine measurement
EFO:0004531	urate measurement
EFO:0004348	hematocrit
EFO:0007986	reticulocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4034 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6108160	Efficacy	3	Selective serotonin reuptake inhibitors	Depression

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2745761	PLCB1		0.00	0
rs6108160	PLCB1	3	3.00	1	Selective serotonin reuptake inhibitors

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphoinositide-specific phospholipase C

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	7
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	6
Aflatoxin B1	affects expression, affects methylation, decreases expression	4
bisphenol A	affects methylation, decreases methylation, increases expression, decreases expression, affects cotreatment	3
trichostatin A	decreases expression, increases expression	2
bisphenol S	decreases expression, affects cotreatment, increases methylation	2
Estradiol	increases expression	2
Zearalenone	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Genistein	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
potassium perchlorate	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
dibenzo(a,l)pyrene	decreases expression	1
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

11 unique, capped per target: 9 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL760998	Binding	Critical Micellar Concentration for the compound was calculated for phospholipase C from Bacillus cereus	Enzymatic synthesis of a modified phospholipid and its evaluation as a substrate for B. cereus phospholipase C. — Bioorg Med Chem Lett
CHEMBL761003	Functional	Agonistic activity against phospholipase C (PLC) was determined in adult rat hippocampal slices	(2R,1’S,2’R,3’S)-2-(2’-Carboxy-3’-phenylcyclopropyl)glycine (PCCG-13), the first potent and selective competitive antagonist of phospholipase D-coupled metabotropic glutamate receptors: asymmetric synthesis and preliminary biological properties. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2B4	Abcam HeLa PLCB1 KO	Cancer cell line	Female
CVCL_D8T8	Ubigene HCT 116 PLCB1 KO	Cancer cell line	Male
CVCL_TE20	HAP1 PLCB1 (-) 1	Cancer cell line	Male
CVCL_TE21	HAP1 PLCB1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT03490487	PHASE4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	PHASE4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT00441896	PHASE2	COMPLETED	A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
NCT00442104	PHASE2	TERMINATED	Open-label Extension to Protocol 1042-0500
NCT02829827	PHASE2	TERMINATED	A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
NCT03976076	PHASE2	TERMINATED	A Study of Orally Administered JBPOS0101 in Refractory Infantile Spasms Patients
NCT06819670	PHASE2	RECRUITING	A Study to Prevent Infantile Spasms Relapse
NCT01006811	PHASE2/PHASE3	COMPLETED	Use of the Modified Atkins Diet in Infantile Spasms
NCT01549288	PHASE2/PHASE3	WITHDRAWN	Trial of the Modified Atkins Diet in Infantile Spasms Refractory to Hormonal Therapy
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT06201897	PHASE2/PHASE3	RECRUITING	Cortical Excitability in West Syndrome Using Transcranial Magnetic Stimulation
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00552045	Not specified	COMPLETED	Epilepsy Phenome/Genome Project
NCT00968136	Not specified	COMPLETED	Short-term Ketogenic Diet as Compared With Conventional Long-term Trial in Refractory Infantile Spasms: A Randomized, Controlled Study
NCT01073579	Not specified	COMPLETED	Sabril Patient Registry
NCT01367964	Not specified	UNKNOWN	Prevention of West Syndrome With Low-dose Adrenocorticotropin Hormone (ACTH)
NCT01723787	Not specified	COMPLETED	Genetic Studies in Patients and Families With Infantile Spasms
NCT02220114	Not specified	COMPLETED	Acceptability Study of a New Paediatric Form of Vigabatrin in Infants and Children With Infantile Spasms or Pharmacoresistant Partial Epilepsy
NCT02885389	Not specified	COMPLETED	Molecular Genetics in Infantile Spasms
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05126914	Not specified	RECRUITING	Multicentre Real-life Follow-up Study of Rare Epileptic Syndromes in Children and Adolescents
NCT06315829	Not specified	COMPLETED	Artificial Intelligence-based Video Analysis to Detect Infantile Spasms
NCT01046760	Not specified	UNKNOWN	Scholar Performance and Praxis Assessment in Children With Rolandic Epilepsy
NCT01335425	Not specified	COMPLETED	The Rolandic Epilepsy/ESES/Landau-Kleffner Syndrome and Correlation With Language Impairment Study
NCT01515436	Not specified	COMPLETED	The Effect of Music Periodicity on Interictal Epileptiform Discharges
NCT03465566	Not specified	UNKNOWN	Emotion Recognition in Benign Epilepsy of Childhood With Centro-Temporal Spikes (BECTS)
NCT03547050	Not specified	COMPLETED	Rolandic Epilepsy Genomewide Association International Study
NCT03865771	Not specified	RECRUITING	Sleep Related Memory Consolidation in Children With Age Related Focal Epilepsy.
NCT04325282	Not specified	COMPLETED	Transcranial Magnetic Stimulation for BECTS
NCT04357236	Not specified	COMPLETED	18F-FDG PET Imaging Analysis of Antiepileptic Drug Response in BECTS
NCT04569708	Not specified	COMPLETED	Sleep Spindles and Memory in Rolandic Epilepsy
NCT06545708	Not specified	RECRUITING	Music Perception in SeLECTs