PLCB1

Chr 20AR

phospholipase C beta 1

Also known as: DEE12, EIEE12, PI-PLC, PLC-154, PLC-I, PLC-beta-1, PLC154, PLCB1A

NCBI Gene: 23236ENSG00000182621UniProt: Q9NQ66

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 12MIM #613722
AR
575
ClinVar variants
30
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PLCB1
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 191 VUS of 575 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.30LOEUF
pLI 0.983
Z-score 6.30
OE 0.19 (0.12–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.83Z-score
OE missense 0.58 (0.53–0.63)
381 obs / 657.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.12–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.53–0.63)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 13 / 69.8Missense obs/exp: 381 / 657.7Syn Z: -1.21

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic11
VUS191
Likely Benign293
Benign56
Conflicting5
19
Pathogenic
11
Likely Pathogenic
191
VUS
293
Likely Benign
56
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
14
0
19
Likely Pathogenic
7
0
4
0
11
VUS
1
165
22
3
191
Likely Benign
0
3
169
121
293
Benign
0
0
56
0
56
Conflicting
—5
Total13168265124575

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PLCB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PLCB1-related epileptic encephalopathy, early infantile

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 12

MIM #613722

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism.
Sun L et al.·Nat Chem Biol
2023
Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas.
Ma K et al.·Drug Resist Updat
2024
Lnc-PLCB1 is stabilized by METTL14 induced m6A modification and inhibits Helicobacter pylori mediated gastric cancer by destabilizing DDX21.
Chang M et al.·Cancer Lett
2024
PLCB1 epileptic encephalopathies; Review and expansion of the phenotypic spectrum.
Schoonjans AS et al.·Eur J Paediatr Neurol
2016Review
Pharmacogenetics of Bronchodilator Response: Future Directions.
Sordillo JE et al.·Curr Allergy Asthma Rep
2021Review
Exportin-5 SUMOylation promotes hepatocellular carcinoma progression.
Lin D et al.·Exp Cell Res
2020
The identification of key molecules and pathways in the crosstalk of calcium oxalate-treated TCMK-1 cells and macrophage via exosomes.
Sun Y et al.·Sci Rep
2024
[Phospholipase Cβ1 (PLCB1) promotes gastric adenocarcinoma metastasis by inducing epithelial mesenchymal transition and inhibiting tumour immune infiltration and is associated with poor patient prognosis].
Yue L et al.·Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
2025
Genetic predisposition to differentiated thyroid cancer in the Polish population.
Borowczyk M et al.·Pol Arch Intern Med
2024
Three novel patients with epileptic encephalopathy due to biallelic mutations in the PLCB1 gene.
Desprairies C et al.·Clin Genet
2020Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools