PLCL2
Chr 3phospholipase C like 2
Also known as: PLCE2
The PLCL2 protein enables GABA receptor binding and is predicted to regulate inositol trisphosphate signaling around the endoplasmic reticulum. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.088), indicating that complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
41 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 23 | 0 | 23 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 1 | 0 | 0 | 1 |
Likely Benign | 0 | 0 | 0 | 8 | 8 |
Benign | 1 | 1 | 0 | 1 | 3 |
| Total | 1 | 2 | 24 | 9 | 36 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PLCL2 · 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