PLCE1

Chr 10AR

phospholipase C epsilon 1

Also known as: NPHS3, PLCE, PPLC

This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nephrotic syndrome, type 3MIM #610725
AR

Clinical highlights

Gene-disease validity (ClinGen)
nephrotic syndrome, type 3 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
0.46
LOEUF
LOF
Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.46LOEUF
pLI 0.000
Z-score 6.30
OE 0.35 (0.270.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.38Z-score
OE missense 0.89 (0.840.93)
1061 obs / 1195.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.35 (0.270.46)
00.351.4
Missense OE?0.89 (0.840.93)
00.61.4
Synonymous OE?0.96
01.21.6
LoF obs/exp: 39 / 110.4Missense obs/exp: 1061 / 1195.4Syn Z: 0.61

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PLCE1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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