PDE2A

protein-coding

phosphodiesterase 2A, the group of Phosphodiesterases|MicroRNA protein coding host genes

Gene summary

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]

MANE transcript

NM_002599.5

Inheritance

ClinVar variants

P:8U:145B:101

Top phenotype

Intellectual developmental disorder with paroxysmal dyskinesia or seizures

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr11:72,576,141-72,674,591

External References & Databases

Ensembl (ENSG00000186642)

Transcript & Mutation Effects

hg38 • Region Span ~98.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with paroxysmal dyskinesia or seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030900

Submitter: PanelApp Australia

intellectual developmental disorder with paroxysmal dyskinesia or seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030900

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder with paroxysmal dyskinesia or seizuresAR

Manifestation: Craniofacial; Neurologic

Intervention: Neurologic

Rationale: While the seizures have been desribed as refractory to antieepileptic mediactions, medical management (eg, with vigabatrin) has been reported as transiently improving the neurologic abnormalities in an individual, and deep brain neurostimulation has been described as resulting in clinical improvement of the movement disorder

Refs: 29392776; 32196122; 32467598

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDE2A variants in ClinVar

12 Conditions Cataloged

not providedTotal: 268

Inborn genetic diseasesTotal: 84

Intellectual developmental disorder with paroxysmal dyskinesia or seizuresTotal: 18

not specifiedTotal: 15

PDE2A-related disorderTotal: 6

Moderate intellectual disabilityTotal: 1

Paroxysmal dystoniaTotal: 1

EEG abnormalityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002599.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	94 clinvar	2 clinvar	99
missense	2 clinvar	1 clinvar	133 clinvar	4 clinvar	1 clinvar	141
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	7 clinvar			10
Total	5	3	145	98	3	254

Highest pathogenic variant AF is 0.0000022068268

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002599.5	RefSeq	NP_002590.1	31	MANE Select
ENST00000334456.10	Ensembl	ENSP00000334910.5	31	MANE Select
NM_001143839.4	RefSeq	NP_001137311.1	30	Standard
NM_001146209.3	RefSeq	NP_001139681.1	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aldosterone synthesis and secretion - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
cGMP-PKG signaling pathway - Homo sapiens (human)
Olfactory transduction - Homo sapiens (human)
Morphine addiction - Homo sapiens (human)

Biological Process

negative regulation of transcription by RNA polymerase II
G protein-coupled receptor signaling pathway
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
positive regulation of gene expression
negative regulation of cGMP-mediated signaling

Molecular Function

magnesium ion binding
3',5'-cyclic-AMP phosphodiesterase activity
cGMP-stimulated cyclic-nucleotide phosphodiesterase activity
calcium channel activity
protein binding

Cellular Component

nucleus
cytoplasm
mitochondrial outer membrane
mitochondrial inner membrane
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334456
Coding exons: 31
Length: 98451
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.06	271	535	0.507	0.0000284	6172
Missense (PolyPhen)		43	177.48	0.24229		1917
Synonymous	0.381	214	221	0.967	0.0000126	1750
Loss of Function	5.44	12	55.9	0.215	0.00000266	635

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000099	0.000079	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cyclic nucleotide phosphodiesterase with a dual- specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Plays an important role in growth and invasion of malignant melanoma cells (e.g. pseudomyxoma peritonei (PMP) cell line) (PubMed:24705027). {ECO:0000269|PubMed:24705027}.;

Recessive Scores

pRec: 0.183

Intolerance Scores

LoFtool: 0.400
RVIS EVS: -1.09
RVIS percentile EVS: 7.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.664

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium