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PDE2A phosphodiesterase 2A [ Homo sapiens (human) ]

Gene ID: 5138, updated on 11-Apr-2024

Summary

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Official Symbol
PDE2Aprovided by HGNC
Official Full Name
phosphodiesterase 2Aprovided by HGNC
Primary source
HGNC:HGNC:8777
See related
Ensembl:ENSG00000186642 MIM:602658; AllianceGenome:HGNC:8777
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PDE2A1; PED2A4; cGSPDE; CGS-PDE; IDDPADS
Summary
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 organic cyclic compound; cyclic-nucleotide-mediated signaling; and regulation of vascular permeability. Located in several cellular components, including cytosol; mitochondrial membrane; and perinuclear region of cytoplasm. Colocalizes with plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in spleen (RPKM 45.0), brain (RPKM 27.8) and 14 other tissues See more
Orthologs
mouse all
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Genomic context

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See PDE2A in Genome Data Viewer
Location:
11q13.4
Exon count:
35
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (72576141..72674422, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (72502658..72602659, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (72287185..72385466, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene cyclic nucleotide gated channel subunit alpha 1 pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr11:72273300-72273507 Neighboring gene long intergenic non-protein coding RNA 1537 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72295333-72295856 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72295857-72296378 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3721 Neighboring gene PDE2A antisense RNA 2 Neighboring gene uncharacterized LOC105369377 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5192 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72329425-72329944 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72336883-72337427 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72337428-72337971 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:72339671-72340196 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72340723-72341248 Neighboring gene RNA, U7 small nuclear 105 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72341249-72341773 Neighboring gene microRNA 139 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72344820-72345416 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72345417-72346012 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72353123-72353623 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72354058-72354647 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72363808-72364353 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72367701-72368202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72373037-72373701 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72375031-72375693 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72379106-72379610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5193 Neighboring gene PDE2A antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72384035-72384661 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72384662-72385287 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72385288-72385914 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72385915-72386539 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72386690-72387190 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3723 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72391485-72392310 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:72395779-72396338 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3724 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:72415096-72415932 Neighboring gene ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:72417010-72417596 Neighboring gene ARAP1 antisense RNA 2 Neighboring gene ribosomal protein S12 pseudogene 20

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Low Expression of Phosphodiesterase 2 (PDE2A) Promotes the Progression by Regulating Mitochondrial Morphology and ATP Content and Predicts Poor Prognosis in Hepatocellular Carcinoma. Chen L, et al. Cells, 2022 Dec 23. PMID 36611861, Free PMC Article
  2. Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia. Doummar D, et al. Eur J Hum Genet, 2020 Oct. PMID 32467598, Free PMC Article
  3. A Novel Inhibition Modality for Phosphodiesterase 2A. Nakashima K, et al. SLAS Discov, 2020 Jun. PMID 32343157
  4. A Homozygous Splicing Mutation in PDE2A in a Family With Atypical Rett Syndrome. Haidar Z, et al. Mov Disord, 2020 May. PMID 32196122
  5. Role of phosphodiesterase 2 in growth and invasion of human malignant melanoma cells. Hiramoto K, et al. Cell Signal, 2014 Sep. PMID 24705027, Free PMC Article

See all (50) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The phosphodiesterase 2A controls lymphatic junctional maturation via cGMP-dependent notch signaling.
    Title: The phosphodiesterase 2A controls lymphatic junctional maturation via cGMP-dependent notch signaling.
  2. Low Expression of Phosphodiesterase 2 (PDE2A) Promotes the Progression by Regulating Mitochondrial Morphology and ATP Content and Predicts Poor Prognosis in Hepatocellular Carcinoma.
    Title: Low Expression of Phosphodiesterase 2 (PDE2A) Promotes the Progression by Regulating Mitochondrial Morphology and ATP Content and Predicts Poor Prognosis in Hepatocellular Carcinoma.
  3. miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/beta-catenin signaling.
    Title: miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/β-catenin signaling.
  4. Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.
    Title: Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.
  5. Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease.
    Title: Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease.
  6. A Novel Inhibition Modality for Phosphodiesterase 2A.
    Title: A Novel Inhibition Modality for Phosphodiesterase 2A.
  7. Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy.
    Title: Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy.
  8. Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.
    Title: Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.
  9. A Homozygous Splicing Mutation in PDE2A in a Family With Atypical Rett Syndrome.
    Title: A Homozygous Splicing Mutation in PDE2A in a Family With Atypical Rett Syndrome.
  10. the well-known interaction between AIP and 2 different isoforms of phosphodiesterases (PDEs), PDE2A3 and PDE4A5, is of particular interest. While the interaction with over-expressed AIP does not seem to affect PDE2A3 function, the reported effect on PDE4A5 is, in contrast, reduced enzymatic activity.
    Title: Role of Phosphodiesterases on the Function of Aryl Hydrocarbon Receptor-Interacting Protein (AIP) in the Pituitary Gland and on the Evaluation of AIP Gene Variants.
Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Intellectual developmental disorder with paroxysmal dyskinesia or seizures
MedGen: C5436894 OMIM: 619150 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.
EBI GWAS Catalog
Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat decreases the intracellular levels of cAMP and CREB ser-133 phosphorylation through a signal transduction pathway involving sequential activation of phosphatidylinositol 3-kinase, AKT, and cyclic nucleoside phosphodiesterases PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 3',5'-cyclic-AMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 3',5'-cyclic-AMP phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 3',5'-cyclic-GMP phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables TPR domain binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables cAMP binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables cGMP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cGMP binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables cGMP-stimulated cyclic-nucleotide phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cGMP-stimulated cyclic-nucleotide phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphate ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within aorta development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cAMP-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cAMP-mediated signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cGMP catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cGMP catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cGMP-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cGMP-mediated signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to 2,3,7,8-tetrachlorodibenzodioxine IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to cAMP IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to cGMP IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to macrophage colony-stimulating factor stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to mechanical stimulus ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to transforming growth factor beta stimulus IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in establishment of endothelial barrier ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within heart valve development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cAMP-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of cGMP-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of vascular permeability IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of gene expression IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of vascular permeability IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of cAMP-mediated signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of cGMP-mediated signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of mitochondrion organization IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within ventricular septum development ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in Golgi apparatus ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in mitochondrial inner membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial inner membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrial matrix IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in mitochondrial outer membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial outer membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in perinuclear region of cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
colocalizes_with plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in presynaptic membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in synaptic membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
cGMP-dependent 3',5'-cyclic phosphodiesterase
Names
cGMP-stimulated phosphodiesterase 1
cGMP-stimulated phosphodiesterase 2
cGMP-stimulated phosphodiesterase 4
cyclic GMP-stimulated phosphodiesterase
phosphodiesterase 2A, cGMP-stimulated
NP_001137311.1
NP_001139681.1
NP_001230713.1
NP_002590.1
XP_005274097.1
XP_054225080.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001143839.4 → NP_001137311.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (PDE2A2) is shorter and has a distinct N-terminus, compared to isoform PDE2A3. This variant (2) is assembled from partial human transcripts. The full-length exon combination is inferred from the mouse ortholog (NM_001143849.1, see PMID: 21724846)
    Source sequence(s)
    AP003065, AP005019
    Consensus CDS
    CCDS44670.1
    UniProtKB/TrEMBL
    Q8IW54
    Related
    ENSP00000442256.1, ENST00000544570.5
    Conserved Domains (2) summary
    smart00065
    Location:402 → 551
    GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
    pfam00233
    Location:648 → 878
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  2. NM_001146209.3 → NP_001139681.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform, PDE2A4 (AY495087.1), is shorter and has a distinct N-terminus, compared to isoform PDE2A3.
    Source sequence(s)
    AP003065, AP005019
    Consensus CDS
    CCDS53678.1
    UniProtKB/TrEMBL
    Q8IW54
    Related
    ENSP00000446399.1, ENST00000540345.5
    Conserved Domains (2) summary
    smart00065
    Location:400 → 549
    GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
    pfam00233
    Location:646 → 879
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  3. NM_001243784.2 → NP_001230713.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A1

    See identical proteins and their annotated locations for NP_001230713.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The encoded isoform (PDE2A1) is shorter and has a distinct N-terminus, compared to isoform 1. This variant (2) is assembled from partial human transcripts. The full-length exon combination is inferred from the mouse ortholog (NM_001243757.1, see PMID: 19632989)
    Source sequence(s)
    AP003065, AP005019
    Consensus CDS
    CCDS73345.1
    UniProtKB/TrEMBL
    Q8IW54
    Related
    ENSP00000411657.3, ENST00000444035.6
    Conserved Domains (2) summary
    smart00065
    Location:388 → 537
    GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
    pfam00233
    Location:634 → 867
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  4. NM_002599.5 → NP_002590.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform PDE2A3

    See identical proteins and their annotated locations for NP_002590.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform, PDE2A3 (see PMID:9210593).
    Source sequence(s)
    AP003065, AP005019
    Consensus CDS
    CCDS8216.1
    UniProtKB/Swiss-Prot
    B2R646, B3KRV5, E9PGI1, F6W5Z0, O00408, Q5J791, Q5J792, Q5J793, Q6ZMR1
    UniProtKB/TrEMBL
    Q8IW54
    Related
    ENSP00000334910.5, ENST00000334456.10
    Conserved Domains (2) summary
    smart00065
    Location:409 → 558
    GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
    pfam00233
    Location:655 → 885
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    72576141..72674422 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005274040.4 → XP_005274097.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1

    UniProtKB/TrEMBL
    Q8IW54
    Conserved Domains (2) summary
    smart00065
    Location:408 → 557
    GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
    pfam00233
    Location:654 → 887
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    72502658..72602659 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054369105.1 → XP_054225080.1  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O00408.1 GenPept UniProtKB/Swiss-Prot:O00408

Gene LinkOut

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