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): 188 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 20 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 24
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_000932
• Notable: 188 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 19 — 16 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000279230

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1

ENST00000279230, ENST00000325234, ENST00000536243, ENST00000540288, ENST00000885806, ENST00000885807, ENST00000885808, ENST00000885809, ENST00000885811, ENST00000885813, ENST00000885814, ENST00000885815, ENST00000922180, ENST00000922181, ENST00000979815, ENST00001013275, ENST00001013276, ENST00001120670, ENST00001140774

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.

Highest expression (Bgee): lower esophagus mucosa, mucosa of transverse colon, small intestine Peyer’s patch, tendon of biceps brachii, small intestine.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLCB3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 27 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	8.7e-37	-0.41	11:64322950:G:A
Artery Tibial	sqtl	1.2e-06	-0.80	11:64259996:T:C
Artery Tibial	eqtl	4.1e-06	+0.44	11:64129874:C:G
Nerve Tibial	sqtl	5.7e-06	-0.87	11:64317591:G:C
Adipose Subcutaneous	sqtl	2.0e-05	+0.68	11:64266276:T:C
Brain Cerebellum	eqtl	9.1e-05	+0.33	11:64402802:G:A
Testis	eqtl	2.4e-04	+0.57	11:65056529:A:G
Brain Cerebellar Hemisphere	eqtl	2.5e-04	-0.35	11:64343211:G:C
Skin Sun Exposed Lower leg	sqtl	3.4e-04	+0.65	11:64259996:T:C
Whole Blood	eqtl	6.2e-04	-0.09	11:64279169:C:T
Thyroid	sqtl	9.0e-04	-0.63	11:64259996:T:C
Brain Cortex	eqtl	1.4e-03	+0.19	11:64256576:G:C
Cells EBV-transformed lymphocytes	eqtl	1.5e-03	-0.46	11:64112182:C:A
Skin Sun Exposed Lower leg	eqtl	1.7e-03	+0.08	11:64258672:G:A
Esophagus Muscularis	eqtl	2.7e-03	+0.56	11:64145630:C:T
Nerve Tibial	eqtl	5.6e-03	+0.08	11:64245438:A:G
Spleen	eqtl	5.6e-03	-0.21	11:64302069:T:C
Heart Left Ventricle	eqtl	5.8e-03	-0.29	11:64413244:C:T
Muscle Skeletal	eqtl	7.9e-03	+0.13	11:64271703:G:A
Brain Hippocampus	eqtl	1.2e-02	+0.27	11:64117833:C:T

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 271 tissues 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
descending thoracic aorta	UBERON:0002345	85.79	gold quality
coronary artery	UBERON:0001621	85.75	gold quality
skin of leg	UBERON:0001511	85.48	gold quality
popliteal artery	UBERON:0002250	85.46	gold quality
left ovary	UBERON:0002119	85.45	gold quality
tibial artery	UBERON:0007610	85.43	gold quality
skin of abdomen	UBERON:0001416	85.38	gold quality
lower esophagus	UBERON:0013473	85.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.03	gold quality
apex of heart	UBERON:0002098	84.97	gold quality
upper lobe of left lung	UBERON:0008952	84.96	gold quality
mucosa of stomach	UBERON:0001199	84.95	gold quality
metanephros cortex	UBERON:0010533	84.70	gold quality
adrenal gland	UBERON:0002369	84.56	gold quality
endometrium epithelium	UBERON:0004811	84.55	gold quality
body of stomach	UBERON:0001161	84.41	gold quality
jejunal mucosa	UBERON:0000399	84.24	gold quality
colon	UBERON:0001155	84.16	gold quality
omental fat pad	UBERON:0010414	83.98	gold quality
minor salivary gland	UBERON:0001830	83.96	gold quality
peritoneum	UBERON:0002358	83.92	gold quality
large intestine	UBERON:0000059	83.85	gold quality
upper lobe of lung	UBERON:0008948	83.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.27	gold quality
right lung	UBERON:0002167	83.09	gold quality
pancreatic ductal cell	CL:0002079	83.04	silver quality
adipose tissue of abdominal region	UBERON:0007808	83.02	gold quality
right lobe of thyroid gland	UBERON:0001119	82.83	gold quality
mouth mucosa	UBERON:0003729	82.79	gold quality
granulocyte	CL:0000094	82.75	gold quality
rectum	UBERON:0001052	82.63	gold quality
spleen	UBERON:0002106	82.58	gold quality
ovary	UBERON:0000992	82.40	gold quality
tibial nerve	UBERON:0001323	82.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.30	gold quality
sural nerve	UBERON:0015488	82.29	gold quality
zone of skin	UBERON:0000014	82.22	gold quality
stomach	UBERON:0000945	82.16	gold quality
monocyte	CL:0000576	82.07	gold quality
right atrium auricular region	UBERON:0006631	81.89	gold quality
saliva-secreting gland	UBERON:0001044	81.66	gold quality
mononuclear cell	CL:0000842	81.59	gold quality
sigmoid colon	UBERON:0001159	81.52	gold quality
leukocyte	CL:0000738	81.36	gold quality
left lobe of thyroid gland	UBERON:0001120	81.36	gold quality
cerebellar hemisphere	UBERON:0002245	81.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.96	gold quality
ventricular zone	UBERON:0003053	80.93	gold quality
cerebellar cortex	UBERON:0002129	80.87	gold quality
thyroid gland	UBERON:0002046	80.41	gold quality
heart left ventricle	UBERON:0002084	80.28	gold quality
gall bladder	UBERON:0002110	80.04	gold quality
subcutaneous adipose tissue	UBERON:0002190	79.74	gold quality
cardiac ventricle	UBERON:0002082	79.73	gold quality
cardiac atrium	UBERON:0002081	79.61	gold quality
prostate gland	UBERON:0002367	79.56	gold quality
heart	UBERON:0000948	79.51	gold quality
ganglionic eminence	UBERON:0004023	79.12	gold quality
gastrocnemius	UBERON:0001388	78.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.65	gold quality
cerebellum	UBERON:0002037	78.60	gold quality
fundus of stomach	UBERON:0001160	78.48	gold quality
female reproductive system	UBERON:0000474	78.39	gold quality
muscle of leg	UBERON:0001383	78.03	gold quality
smooth muscle tissue	UBERON:0001135	78.02	gold quality
right uterine tube	UBERON:0001302	77.98	gold quality
myometrium	UBERON:0001296	77.97	gold quality
adipose tissue	UBERON:0001013	77.92	gold quality
right lobe of liver	UBERON:0001114	77.73	gold quality
anatomical system	UBERON:0000467	77.61	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Duodenum	tissue	107.1	medium
Small intestine	tissue	95.7	medium
Skin 1	tissue	19.2	not detected
Vagina	tissue	18.1	not detected
Colon	tissue	17.4	low
Esophagus	tissue	15.2	not detected
Stomach 1	tissue	13.9	not detected
Spinal cord	tissue	12.8
Rectum	tissue	11.7	low
Choroid plexus	tissue	11.3
Smooth muscle	tissue	10.6	not detected
Superior colliculi	tissue	10.6
Medulla oblongata	tissue	10.5
Substantia nigra	tissue	10.2
Spleen	tissue	10.1	not detected
Seminal vesicle	tissue	9.8	not detected
Caudate putamen	tissue	9.8
Thalamus	tissue	9.7
Placenta	tissue	9.7	not detected
Adrenal gland	tissue	9.7	not detected
Pons	tissue	9.5
Parathyroid gland	tissue	9.4	not detected
Midbrain	tissue	9.4
Lung	tissue	9.4	low
Hippocampus	tissue	9.3	not detected
Hypothalamus	tissue	9.2
Appendix	tissue	9.2	medium
Locus coeruleus	tissue	8.9
Periaqueductal gray	tissue	8.9
Salivary gland	tissue	8.7	not detected
Frontal cortex	tissue	8.6
Adipose tissue	tissue	8.5	not detected
Hippocampal formation	tissue	8.5
Ovary	tissue	8.4	not detected
Cerebral cortex	tissue	8.3	not detected
Urinary bladder	tissue	8.3	low
Motor cortex	tissue	8.3
Amygdala	tissue	8.3
Endometrium 1	tissue	8.1	not detected
Nucleus accumbens	tissue	8.0
Septum	tissue	7.4
Prefrontal cortex	tissue	7.3
Corpus callosum	tissue	7.3
Fallopian tube	tissue	7.3	not detected
Insular cortex	tissue	7.2
Cervix	tissue	7.1	low
Entorhinal cortex	tissue	7.1
Bone marrow	tissue	7.0	not detected
Somatosensory cortex	tissue	7.0
Temporal cortex	tissue	7.0
Putamen	tissue	6.9
Ventral forebrain	tissue	6.9
Retrosplenial cortex	tissue	6.7
Gallbladder	tissue	6.6	low
Basal ganglia	tissue	6.4	not detected
Cerebellum	tissue	6.4	medium
Retrosplenial and cingulate cortex	tissue	6.3
Occipital cortex	tissue	6.3
Postcentral gyrus	tissue	6.1
Prostate	tissue	6.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Posterior thalamic nucleus (16.1), Anterior thalamic nucleus, ventral (15.9), Inferior olive (15.9), Blood vessel (15.8), Area postrema (15.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PLCB3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 56 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.995, LOEUF 0.468, missense Z 3.71 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000279230 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:64,251,650–64,256,716	299 / 434.7	0.69	no
11:64,256,717–64,256,756	1 / 16.1	0.06	yes (p 1.7e-04)
11:64,256,757–64,259,185	122 / 221.8	0.55	no
11:64,259,186–64,260,206	105 / 100.9	1.04	no
11:64,260,207–64,264,076	244 / 424.4	0.57	no
11:64,264,077–64,267,553	477 / 489.6	0.97	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104778) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
spontaneous skin ulceration	1
abnormal extraembryonic tissue morphology	1
absent blastocoele	1
abnormal calcium ion homeostasis	1
analgesia	1
embryonic lethality before implantation, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RET0	98.4%	Diamond
Bos taurus	P10894	97.1%	Diamond
Macaca fascicularis	Q4R6L3	91.4%	Diamond
Sus scrofa	Q8SPR7	85.8%	Diamond
Arabidopsis thaliana	Q39033	80.4%	Diamond
Xenopus laevis	Q32NH8	60.5%	Diamond
Gallus gallus	Q2VRL0	59.6%	Diamond
Caenorhabditis elegans	G5EBH0	52.5%	Diamond
Dictyostelium discoideum	Q02158	37.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FKBP2	protein-coding	2286
PPP1R14B	protein-coding	26472
GPR137	protein-coding	56834
BAD	protein-coding	572
VEGFB	protein-coding	7423
ESRRA	protein-coding	2101
PRDX5	protein-coding	25824
CATSPERZ	protein-coding	25858
KCNK4	protein-coding	50801
TRMT112	protein-coding	51504
PPP1R14B-AS1	ncRNA	105369340
DNAJC4	protein-coding	3338
KCNK4-CATSPERZ	ncRNA	106780802

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. In conjunction with OSBPL2, it may contribute to the control of keratinocyte proliferation and differentiation, probably through the regulation of the ERK pathway and the cell cycle.

Subunit / interactions. Interacts with SHANK2. Interacts with LPAR2. Interacts with OSBPL2; the interaction inhibits PLCB3 ubiquitination and degradation.

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)

• 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 (135 total): helix 48, strand 42, modified residue 7, mutagenesis site 7, compositionally biased region 5, turn 5, binding site 4, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7SQ2	Reprocessed and refined structure of Phospholipase C-beta and Gq signaling complex	X-RAY DIFFRACTION	2.6
4QJ3	Structure of a fragment of human phospholipase C-beta3 delta472-559, in complex with …	X-RAY DIFFRACTION	3
4QJ4	Structure of a fragment of human phospholipase C-beta3 delta472-569, bound to IP3 and in …	X-RAY DIFFRACTION	3.3
8EMX	Phospholipase C beta 3 (PLCb3) in complex with Gbg on lipid nanodiscs	ELECTRON MICROSCOPY	3.3
8UQO	PLCb3-Gbg-Gaq complex on membranes	ELECTRON MICROSCOPY	3.37
8UQN	PLCb3-Gaq complex on membranes	ELECTRON MICROSCOPY	3.4
4QJ5	Structure of a fragment of human phospholipase C-beta3 delta472-581, bound to IP3 and in …	X-RAY DIFFRACTION	3.41
8EMW	Phospholipase C beta 3 (PLCb3) in complex with Gbg on liposomes	ELECTRON MICROSCOPY	3.5
8EMV	Phospholipase C beta 3 (PLCb3) in solution	ELECTRON MICROSCOPY	3.6
4GNK	Crystal structure of Galphaq in complex with full-length human PLCbeta3	X-RAY DIFFRACTION	4
9Y7H	Gb1g2 crosslinked to PLCb3	ELECTRON MICROSCOPY	4.4
9YAP	Gbg crosslinked to PLCb3 - second conformation	ELECTRON MICROSCOPY	4.5
9YAO	Gbg crosslinked to PLCb3 - second conformation	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the musculoskeletal system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
332
379

Ligand- & substrate-binding residues (4)

Position	Role
333	Ca(2+)
362	Ca(2+)
364	Ca(2+)
413	Ca(2+)

Post-translational modifications (7)

Type	Positions
N-acetylalanine	2
Phosphoserine	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

4 curated (TAS) of 26; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

26 pathways:

ID	Pathway	Evidence
R-HSA-4086398	Ca2+ pathway	curated
R-HSA-418217	G beta:gamma signalling through PLC beta	curated
R-HSA-500657	Presynaptic function of Kainate receptors	curated
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol	curated
R-HSA-399997	Acetylcholine regulates insulin secretion	electronic
R-HSA-451326	Activation of kainate receptors upon glutamate binding	—
R-HSA-3858494	Beta-catenin independent WNT signaling	—
R-HSA-434316	Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	electronic
R-HSA-400451	Free fatty acids regulate insulin secretion	—
R-HSA-418594	G alpha (i) signalling events	—
R-HSA-416476	G alpha (q) signalling events	electronic
R-HSA-397795	G-protein beta:gamma signalling	—
R-HSA-112040	G-protein mediated events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-1483249	Inositol phosphate metabolism	—
R-HSA-163685	Integration of energy metabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-111885	Opioid Signalling	—
R-HSA-112043	PLC beta mediated events	electronic
R-HSA-422356	Regulation of insulin secretion	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-195721	Signaling by WNT	—
R-HSA-112315	Transmission across Chemical Synapses	—

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 (11): 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)

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 (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), protein-containing complex (GO:0032991), postsynaptic cytosol (GO:0099524), nucleus (GO:0005634)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Metabolism	2
Signal Transduction	2
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
G alpha (i) signalling events	1
Opioid Signalling	1
Transmission across Chemical Synapses	1
Neuronal System	1
Signaling by WNT	1

GO top-level categories

38 GO namespaces:

Category	Terms
cellular anatomical structure	4
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
glycerophospholipid metabolic process	1
intracellular signal transduction	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
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
nuclear lumen	1
cytoplasm	1
cellular_component	1
cytosol	1
postsynapse	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
phosphatidylinositol metabolic process	BP	direct assay
phospholipase C-activating G protein-coupled receptor signaling pathway	BP	direct assay
phospholipase C-activating serotonin receptor signaling pathway	BP	direct assay
regulation of systemic arterial blood pressure	BP	direct assay
cytoplasm	CC	direct assay
nucleoplasm	CC	direct assay
postsynaptic cytosol	CC	direct assay
protein-containing complex	CC	direct assay
cadherin binding	MF	high-throughput assay
calmodulin binding	MF	direct assay
molecular adaptor activity	MF	direct assay
molecular function activator activity	MF	experiment
phosphatidylinositol-4,5-bisphosphate phospholipase C activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,360 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCB3	CHRM1	P11229	782
PLCB3	FKBP2	P26885	779
PLCB3	PYGM	P11217	778
PLCB3	AHNAK	Q09666	767
PLCB3	SF1	Q15637	762
PLCB3	MAP3K11	Q16584	761
PLCB3	COX8A	P10176	760
PLCB3	CAPN1	P07384	760
PLCB3	FTH1	P02794	759
PLCB3	ROM1	Q03395	759
PLCB3	FOSL1	P15407	759
PLCB3	SLC3A2	P08195	759
PLCB3	MARK2	Q7KZI7	758
PLCB3	GNAQ	P50148	735
PLCB3	MEN1	O00255	702

IntAct

Human interaction partners of PLCB3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
NHERF1	physical association	0.560	1
PARD3	physical association	0.520	5
PARD6A	physical association	0.520	2
EZR	physical association	0.400	1
C8orf76	association	0.350	1
MAG	association	0.350	1

BioGRID (118 interactions; top human partners by supporting records): SLC9A3R2 (Two-hybrid; 5 records), KRIT1 (Reconstituted Complex; 2 records), LPAR2 (Reconstituted Complex; 2 records), PRKAR1A (Affinity Capture-MS; 2 records), RAC1 (Affinity Capture-MS; 2 records), ACRC (Cross-Linking-MS (XL-MS)), ADD1 (Co-fractionation), AGPAT3 (Affinity Capture-MS), ANAPC16 (Affinity Capture-MS), AP2S1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), C8orf76 (Affinity Capture-MS), CAB39L (Affinity Capture-MS), CAMSAP2 (Co-fractionation), CDC42 (Proximity Label-MS)

SIGNOR signaling

showing 10 of 12 signaling 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

Protein complexes (CORUM) (9)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

9 complexes by size:

Complex	Subunits	Members
PARD3-PARD6A-PLCB3 complex	3	PARD3, PARD6A, PLCB3
LPAR2-NHERF2-PLCB3 complex	3	LPAR2, NHERF2, PLCB3
CXCR2-SLC9A3R1-PLCB3 complex	3	CXCR2, NHERF1, PLCB3
★ PDZK1-PLCB3-SSTR5 complex	3	PDZK1, PLCB3, SSTR5
★ PDZK1-PLCB3-SSTR1 complex	3	PDZK1, PLCB3, SSTR1
★ PDZK1-PLCB3-SSTR2 complex	3	PLCB3, SSTR2, PDZK1
★ PDZK1-PLCB3-SSTR3 complex	3	SSTR3, PDZK1, PLCB3
★ PDZK1-PLCB3-SSTR4 complex	3	PDZK1, PLCB3, SSTR4
★ CHRM3-PLCB3 complex	2	CHRM3, PLCB3

Disease & clinical

Genetic variants

Variant evidence for PLCB3: 188 ClinVar records (1 pathogenic / likely pathogenic); 17 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	130
Likely benign	22
Benign	8

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1686865	NM_000932.5(PLCB3):c.2632G>T (p.Ala878Ser)	Likely pathogenic	criteria provided, single submitter	2

Per-variant reference — Sugi Variant

Explore PLCB3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 45 predictions of 2,575):

Position(s)	Effect	Δscore	Sites
11:64251749–64251750	donor_loss	1.0000	4
11:64254413–64254414	acceptor_loss	1.0000	5
11:64254746–64254747	acceptor_loss	1.0000	5
11:64255039–64255040	donor_loss	1.0000	5
11:64255394	acceptor_loss	1.0000	3
11:64255822	donor_loss	1.0000
11:64256374–64256375	acceptor_loss	1.0000	6
11:64256543–64256544	donor_loss	1.0000	5
11:64256616–64256617	acceptor_loss	1.0000	6
11:64256765–64256766	donor_loss	1.0000	5

AlphaMissense

3,193 missense substitutions predicted likely pathogenic (of 8,046 scored), across 768 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M590	9	0.963	1.000
M383	9	0.879	0.997
M425	9	0.878	0.998
D364	8	1.000	1.000
H379	8	1.000	1.000
H332	8	0.999	1.000
N414	8	0.999	1.000
H415	8	0.999	1.000
N333	8	0.998	1.000
F412	8	0.995	1.000
N467	8	0.994	1.000
N675	8	0.993	1.000
D71	8	0.982	0.996
D721	8	0.979	0.995
F401	8	0.978	0.999
F712	8	0.978	0.997
D757	8	0.977	0.993
D655	8	0.974	0.996
F602	8	0.973	0.999
F620	8	0.970	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000167
Lung Adenocarcinoma (validation)	unfavorable	0.000223

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
spondylometaphyseal dysplasia with corneal dystrophy	Limited	Unknown	2
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 phenotypes (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:

Study	Trait	p-value
GCST90002397_136	Mean spheric corpuscular volume	8e-21
GCST007500_19	Waist-to-hip ratio adjusted for BMI (additive genetic model)	7e-16
GCST007502_22	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1e-15
GCST007483_32	Waist-to-hip ratio adjusted for BMI (additive genetic model)	9e-15
GCST90002385_518	High light scatter reticulocyte count	6e-14
GCST007487_54	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3e-13
GCST90002386_206	High light scatter reticulocyte percentage of red cells	9e-13
GCST004611_209	High light scatter reticulocyte count	2e-10
GCST90002403_457	Red blood cell count	2e-10
GCST90002389_440	Lymphocyte percentage of white cells	4e-10
GCST004612_155	High light scatter reticulocyte percentage of red cells	1e-9
GCST90002405_506	Reticulocyte count	1e-9
GCST90002397_137	Mean spheric corpuscular volume	2e-9
GCST004785_14	Vitiligo	5e-8
GCST007518_21	Type 2 diabetes (adjusted for BMI)	2e-7
GCST007516_22	Type 2 diabetes (adjusted for BMI)	2e-6
GCST004132_83	Crohn’s disease	5e-6

EFO canonical traits (from GWAS)

4 canonical traits:

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 (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphoinositide-specific phospholipase C

Binding affinities (BindingDB)

154 measured of 155 human assays (157 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2,3,4,5-tetrahydroxy-6-benzo[7]annulenone	IC50	1230 nM
1,6-dimethyl-3-propyl-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1770 nM
1,2-Dione-Based Compound, 14	IC50	1920 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
MLS000775432	IC50	40800 nM
cid_360404	IC50	40800 nM
SMR003100911	IC50	45100 nM
MLS004342426	IC50	47200 nM
SMR003287627	IC50	55400 nM
cid_60159071	IC50	61900 nM
cid_616832	IC50	102000 nM
MLS001332477	IC50	109000 nM
cid_340219	IC50	122000 nM
3-[(2Z)-2-(3-methanoyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)hydrazinyl]benzoic acid	IC50	122000 nM
SMR000114997	IC50	122000 nM
cid_5388680	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
SMR000279973	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
SMR000518325	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
cid_1591868	IC50	122000 nM
SMR000313157	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
2-[(5Z)-5-[(E)-3-(furan-2-yl)prop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanedioic acid	IC50	122000 nM
SMR000125727	IC50	122000 nM
MLS000325723	IC50	122000 nM
SMR000349781	IC50	122000 nM
5-[2-[(5Z)-5-(furan-2-ylmethylidene)-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]propanoylamino]-2-hydroxybenzoic acid	IC50	122000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
bisphenol A	decreases expression	2
Air Pollutants	increases oxidation, increases expression, affects cotreatment, increases abundance	2
Tobacco Smoke Pollution	affects expression	2
Particulate Matter	increases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	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 cotreatment, affects expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLCB3 across ~30M SureChEMBL compounds — explore on Sugi Predict.