PDE2A
Chr 11ARphosphodiesterase 2A
Also known as: CGS-PDE, IDDPADS, PDE2A1, PED2A4, cGSPDE
The protein functions as a cGMP-activated cyclic nucleotide phosphodiesterase that degrades both cGMP and cAMP second messengers, with higher efficiency for cGMP. Biallelic mutations cause intellectual developmental disorder with paroxysmal dyskinesia or seizures, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.348), indicating intolerance to protein-disrupting changes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
200 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 | 1 | 0 | 1 |
Likely Pathogenic | 1 | 0 | 0 | 0 | 1 |
VUS | 5 | 64 | 3 | 0 | 72 |
Likely Benign | 0 | 2 | 45 | 45 | 92 |
Benign | 0 | 0 | 9 | 1 | 10 |
| Total | 6 | 66 | 58 | 46 | 176 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PDE2A · 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