PLCB3

Chr 11AR

phospholipase C beta 3

Also known as: SMDCD

NCBI Gene: 5331ENSG00000149782UniProt: Q01970

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.[provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Spondylometaphyseal dysplasia with corneal dystrophyMIM #618961
AR
185
ClinVar variants
9
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PLCB3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 127 VUS of 185 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.
0.31LOEUF
pLI 0.940
Z-score 6.06
OE 0.20 (0.13–0.31)
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.
3.27Z-score
OE missense 0.67 (0.62–0.72)
512 obs / 766.4 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.0.20 (0.13–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.62–0.72)
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.1.02
0≤1.21.6
LoF obs/exp: 13 / 66.2Missense obs/exp: 512 / 766.4Syn Z: -0.29

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS127
Likely Benign13
Benign8
6
Pathogenic
3
Likely Pathogenic
127
VUS
13
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
1
2
0
3
VUS
0
125
2
0
127
Likely Benign
0
8
0
5
13
Benign
0
4
2
2
8
Total0138127157

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

View in ClinVar →

Protein Context — Lollipop Plot

PLCB3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PLCB3-related spondylometaphyseal dysplasia associated with corneal dystrophy and developmental delay (SMDCD)

limited
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spondylometaphyseal dysplasia with corneal dystrophy

MIM #618961

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Surendran P et al.·Nat Genet
2020Meta-analysis
Cetuximab inhibits colorectal cancer development through inactivating the Wnt/β-catenin pathway and modulating PLCB3 expression.
Zhang X et al.·Sci Rep
2024
PLCB3 Loss of Function Reduces Pseudomonas aeruginosa-Dependent IL-8 Release in Cystic Fibrosis.
Rimessi A et al.·Am J Respir Cell Mol Biol
2018
OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome.
Wang Y et al.·Biochim Biophys Acta Mol Basis Dis
2024
Suppression of the neoplastic phenotype by transfection of phospholipase C beta 3 to neuroendocrine tumor cells.
Stålberg P et al.·FEBS Lett
1999
In situ RNA-RNA hybridisation of phospholipase C beta 3 shows lack of expression in neuroendocrine tumours.
Stålberg P et al.·Anticancer Res
2003
Defect in phosphoinositide signalling through a homozygous variant in PLCB3 causes a new form of spondylometaphyseal dysplasia with corneal dystrophy.
Ben-Salem S et al.·J Med Genet
2018Case report
Tibial cortex transverse transport surgery improves wound healing in patients with severe type 2 DFUs by activating a systemic immune response: a cross-sectional study.
Yu L et al.·Int J Surg
2025Cohort
Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson's Disease.
Yemni EA et al.·Sci Rep
2019
Distinct Prognostic Values of Phospholipase C Beta Family Members for Non-Small Cell Lung Carcinoma.
Zhang T et al.·Biomed Res Int
2019
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