PDE2A

Chr 11AR

phosphodiesterase 2A

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

NCBI Gene: 5138 ENSG00000186642 UniProt: O00408 OMIM: 602658

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables several functions, including 3',5'-cyclic-nucleotide phosphodiesterase activity; anion binding activity; and metal ion binding activity. Involved in several processes, including cGMP catabolic process; cellular response to cytokine stimulus; 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, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with paroxysmal dyskinesia or seizuresMIM #619150

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intellectual developmental disorder with paroxysmal dyskinesia or seizures; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in PDE2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 54

1,178 rare PASS variants

Rare truncating (LoF)

1 in 680

164 rare PASS variants

Rare synonymous (reference)

1 in 68

626 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDE2A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 74	1 in 870
South Asian	~43k	1 in 51	1 in 620
Remaining (unassigned)	~30k	1 in 44	1 in 550
European (Finnish)	~27k	1 in 160	1 in 1,400
Admixed American	~22k	1 in 53	1 in 670
African / African American	~21k	1 in 64	1 in 1,700
East Asian	~20k	1 in 64	1 in 1,700
Ashkenazi Jewish	~13k	1 in 220	1 in 600
Middle Eastern	~2,884	1 in 56	≈ 1 in 930

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 24 of 31 coding exons well covered in gnomAD exomes; exons 2, 3, 6, 8, 14 and 2 more marginal. Genomes: all 31.? see exons ↓