PLCL1
Chr 2phospholipase C like 1 (inactive)
Also known as: PLCE, PLCL, PLDL1, PPP1R127, PRIP
The PLCL1 protein is involved in inositol phospholipid signaling and regulates GABA-A receptor endocytosis, contributing to the maintenance of GABAergic synaptic inhibition. Mutations cause autosomal recessive intellectual disability and epilepsy, typically with infantile onset seizures. The gene is highly constrained against loss-of-function variants (LOEUF 0.476), reflecting its critical role in neurodevelopment and synaptic function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PLCL1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools