PACS2
Chr 14ADphosphofurin acidic cluster sorting protein 2
Also known as: DEE66, EIEE66, PACS-2, PACS1L
PACS2 encodes a protein that maintains endoplasmic reticulum calcium homeostasis and tethers mitochondria to the endoplasmic reticulum. Loss-of-function mutations cause developmental and epileptic encephalopathy 66, inherited in an autosomal dominant pattern. The pathogenic mechanism involves disrupted cellular calcium regulation and impaired mitochondrial-ER communication.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PACS2 · 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
External Resources
Links to major genomics databases and tools