PDE2A

Chr 11AR

phosphodiesterase 2A

Also known as: CGS-PDE, IDDPADS, PDE2A1, PED2A4, cGSPDE

NCBI Gene: 5138ENSG00000186642UniProt: O00408

Enables several functions, including 3',5'-cyclic-nucleotide phosphodiesterase activity; anion binding activity; and metal ion binding activity. Involved in several processes, including cellular response to cytokine stimulus; regulation of signal transduction; and regulation of vascular permeability. Located in several cellular components, including cytosol; mitochondrial membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with paroxysmal dyskinesia or seizuresMIM #619150
AR
364
ClinVar variants
17
Pathogenic / LP
0.63
pLI score
0
Active trials
Clinical Summary— PDE2A
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 150 VUS of 364 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.35LOEUF
pLI 0.631
Z-score 5.44
OE 0.21 (0.14–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.06Z-score
OE missense 0.51 (0.46–0.56)
271 obs / 535.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.14–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.46–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 12 / 55.9Missense obs/exp: 271 / 535.0Syn Z: 0.38

ClinVar Variant Classifications

364 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic3
VUS150
Likely Benign170
Benign25
Conflicting2
14
Pathogenic
3
Likely Pathogenic
150
VUS
170
Likely Benign
25
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
10
0
14
Likely Pathogenic
2
1
0
0
3
VUS
3
128
17
2
150
Likely Benign
0
4
75
91
170
Benign
0
2
16
7
25
Conflicting
—2
Total7137118100364

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder with paroxysmal dyskinesia or seizures

MIM #619150

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).
Trabanco AA et al.·Expert Opin Ther Pat
2016Review
miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/β-catenin signaling.
Li SZ et al.·Int J Biol Sci
2021
Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.
Delhaye S et al.·Mol Psychiatry
2021Review
Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome.
Santana LS et al.·Front Endocrinol (Lausanne)
2022Review
The Emerging Role of Phosphodiesterases in Movement Disorders.
Erro R et al.·Mov Disord
2021Review
A homozygous founder variant in PDE2A causes paroxysmal dyskinesia with intellectual disability.
Yousaf H et al.·Clin Genet
2023
Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.
Rassi-Cruz M et al.·Endocr Relat Cancer
2021
Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.
Doummar D et al.·Eur J Hum Genet
2020Case report
Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes.
Russwurm C et al.·J Biol Chem
2009
Platelet cyclic adenosine monophosphate phosphodiesterases: targets for regulating platelet-related thrombosis.
Colman RW·Semin Thromb Hemost
2004Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools