PDE2A

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

Basic information

Region (hg38): 11:72576141-72674591

Links

ENSG00000186642 ∙ NCBI:5138 ∙ OMIM:602658 ∙ HGNC:8777 ∙ Uniprot:O00408 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile convulsions and choreoathetosis (Supportive), mode of inheritance: AD
• intellectual developmental disorder with paroxysmal dyskinesia or seizures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with paroxysmal dyskinesia or seizures	AR	Neurologic	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	Craniofacial; Neurologic	29392776; 32196122; 32467598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE2A gene.

• not_provided (243 variants)
• Inborn_genetic_diseases (75 variants)
• Intellectual_developmental_disorder_with_paroxysmal_dyskinesia_or_seizures (17 variants)
• PDE2A-related_disorder (2 variants)
• Intellectual_disability,_moderate (1 variants)
• Paroxysmal_dystonia (1 variants)
• EEG_abnormality (1 variants)
• Generalized_hypotonia (1 variants)
• Chorea (1 variants)
• Interictal_EEG_abnormality (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE2A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002599.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	83	3	88
missense	2	1	118	4	1	126
nonsense	1		1			2
start loss						0
frameshift	1					1
splice donor/acceptor (+/-2bp)	1	2	2			5
Total	5	3	123	87	4

Highest pathogenic variant AF is 0.00000220683

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE2A	protein_coding	protein_coding	ENST00000334456	31	98451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.631	0.369	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.06	271	535	0.507	0.0000284	6172
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000988	0.0000791
Middle Eastern	0.000218	0.000217
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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);NO-cGMP-PKG mediated Neuroprotection;Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;actions of nitric oxide in the heart;Purine nucleotides nucleosides metabolism;Hemostasis;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• loftool: 0.400
• rvis_EVS: -1.09
• rvis_percentile_EVS: 7.15

Haploinsufficiency Scores

• pHI: 0.314
• hipred: Y
• hipred_score: 0.756
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.664

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde2a
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• 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;regulation of mitochondrion organization;cAMP-mediated signaling;cGMP-mediated signaling;obsolete negative regulation of protein import into nucleus, translocation;cellular response to drug;cellular response to macrophage colony-stimulating factor stimulus;negative regulation of vascular permeability;positive regulation of vascular permeability;negative regulation of cAMP-mediated signaling;cGMP catabolic process;positive regulation of inflammatory response;establishment of endothelial barrier;calcium ion transmembrane transport;cellular response to mechanical stimulus;cellular response to cAMP;cellular response to cGMP;cellular response to transforming growth factor beta stimulus;cellular response to 2,3,7,8-tetrachlorodibenzodioxine
• Cellular component: nucleus;cytoplasm;mitochondrial outer membrane;mitochondrial inner membrane;mitochondrial matrix;endoplasmic reticulum;Golgi apparatus;cytosol;plasma membrane;presynaptic membrane;perinuclear region of cytoplasm
• Molecular function: magnesium ion binding;3',5'-cyclic-AMP phosphodiesterase activity;cGMP-stimulated cyclic-nucleotide phosphodiesterase activity;calcium channel activity;protein binding;drug binding;zinc ion binding;cAMP binding;cGMP binding;TPR domain binding;phosphate ion binding;protein homodimerization activity;3',5'-cyclic-GMP phosphodiesterase activity