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Aliases for PDE4D Gene

Aliases for PDE4D Gene

  • Phosphodiesterase 4D, CAMP-Specific 2 3
  • DPDE3 3 4 6
  • ACRDYS2 3 6
  • STRK1 3 6
  • PDE43 3 4
  • Phosphodiesterase 4D, CAMP-Specific (Dunce (Drosophila)-Homolog Phosphodiesterase E3) 2
  • Phosphodiesterase 4D, CAMP-Specific (Phosphodiesterase E3 Dunce Homolog, Drosophila) 3
  • Phosphodiesterase E3 Dunce Homolog (Drosophila) 2
  • CAMP-Specific 3,5-Cyclic Phosphodiesterase 4D 3
  • CAMP-Specific Phosphodiesterase PDE4D6 3
  • EC 63
  • EC 4
  • EC 3.1.4 63
  • HSPDE4D 3
  • PDE4DN2 3

External Ids for PDE4D Gene

Previous HGNC Symbols for PDE4D Gene

  • DPDE3

Previous GeneCards Identifiers for PDE4D Gene

  • GC05M058430
  • GC05M059822
  • GC05M058237
  • GC05M058285
  • GC05M058302
  • GC05M055222

Summaries for PDE4D Gene

Entrez Gene Summary for PDE4D Gene

  • This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

GeneCards Summary for PDE4D Gene

PDE4D (Phosphodiesterase 4D, CAMP-Specific) is a Protein Coding gene. Diseases associated with PDE4D include acrodysostosis 2, with or without hormone resistance and acrodysostosis with multiple hormone resistance. Among its related pathways are Signaling by GPCR and Signaling by GPCR. GO annotations related to this gene include enzyme binding and ion channel binding. An important paralog of this gene is PDE7A.

UniProtKB/Swiss-Prot for PDE4D Gene

  • Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Tocris Summary for PDE4D Gene

  • Phosphodiesterases (PDEs) are a family of related phosphohydrolyases that selectively catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). They regulate the cellular levels, localization and duration of action of these second messengers by controlling the rate of their degradation. There are 11 subtypes of PDEs, named PDE1-11; PDE4, 7 and 8 selectively degrade cAMP, PDE5, 6 and 9 selectively degrade cGMP and PDE1, 2, 3, 10 and 11 degrade both cyclic nucleotides. PDEs are expressed ubiquitously, with each subtype having a specific tissue distribution. These enzymes are involved in many signal transduction pathways and their functions include vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, hormone secretion, immune cell activation, and they are involved in learning and memory.

Gene Wiki entry for PDE4D Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PDE4D Gene

Genomics for PDE4D Gene

Regulatory Elements for PDE4D Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for PDE4D Gene

58,969,038 bp from pter
60,522,120 bp from pter
1,553,083 bases
Minus strand

Genomic View for PDE4D Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PDE4D Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDE4D Gene

Proteins for PDE4D Gene

  • Protein details for PDE4D Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    cAMP-specific 3,5-cyclic phosphodiesterase 4D
    Protein Accession:
    Secondary Accessions:
    • O43433
    • Q13549
    • Q13550
    • Q13551
    • Q7Z2L8
    • Q8IV84
    • Q8IVA9
    • Q8IVD2
    • Q8IVD3
    • Q96HL4
    • Q9HCX7

    Protein attributes for PDE4D Gene

    809 amino acids
    Molecular mass:
    91115 Da
    Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Note=Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.;
    Quaternary structure:
    • Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Isoform 5, isoform N3 and isoform 12 bind GNB2L1 via their unique N-terminus. Binds ARRB2. Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.

    Three dimensional structures from OCA and Proteopedia for PDE4D Gene

    Alternative splice isoforms for PDE4D Gene

neXtProt entry for PDE4D Gene

Proteomics data for PDE4D Gene at MOPED

Post-translational modifications for PDE4D Gene

  • Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through phosphorylation (By similarity). Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.
  • Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

Domains for PDE4D Gene

Gene Families for PDE4D Gene

  • PDE :Phosphodiesterases

Protein Domains for PDE4D Gene

Suggested Antigen Peptide Sequences for PDE4D Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Q08499
  • Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
genes like me logo Genes that share domains with PDE4D: view

Function for PDE4D Gene

Molecular function for PDE4D Gene

GENATLAS Biochemistry:
cAMP specific nucleotide phosphodiesterase class IV,D,with homology to Drosophila dunce gene,involved in signal transduction
UniProtKB/Swiss-Prot CatalyticActivity:
Adenosine 3,5-cyclic phosphate + H(2)O = adenosine 5-phosphate
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by rolipram. Activated by phosphatidic acid.
UniProtKB/Swiss-Prot Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Enzyme Numbers (IUBMB) for PDE4D Gene

Gene Ontology (GO) - Molecular Function for PDE4D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004112 cyclic-nucleotide phosphodiesterase activity --
GO:0004114 3,5-cyclic-nucleotide phosphodiesterase activity NAS 10913353
GO:0004115 3,5-cyclic-AMP phosphodiesterase activity IGI 8413254
GO:0005515 protein binding IPI 20664520
GO:0008144 drug binding IPI 15938621
genes like me logo Genes that share ontologies with PDE4D: view
genes like me logo Genes that share phenotypes with PDE4D: view

Animal Models for PDE4D Gene

MGI Knock Outs for PDE4D:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PDE4D

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting and HOMER Transcription for PDE4D Gene

Localization for PDE4D Gene

Subcellular locations from UniProtKB/Swiss-Prot for PDE4D Gene

Apical cell membrane. Cytoplasm. Membrane. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome (By similarity). Colocalized with SHANK2 to the apical membrane of colonic crypt cells. {ECO:0000250}.

Subcellular locations from

Jensen Localization Image for PDE4D Gene COMPARTMENTS Subcellular localization image for PDE4D gene
Compartment Confidence
cytosol 4
cytoskeleton 2
extracellular 1
mitochondrion 1
nucleus 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for PDE4D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IEA --
GO:0005813 centrosome IEA --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton --
GO:0005886 plasma membrane --
genes like me logo Genes that share ontologies with PDE4D: view

Pathways for PDE4D Gene

genes like me logo Genes that share pathways with PDE4D: view

UniProtKB/Swiss-Prot Q08499-PDE4D_HUMAN

  • Pathway: Purine metabolism; 3,5-cyclic AMP degradation; AMP from 3,5-cyclic AMP: step 1/1

Gene Ontology (GO) - Biological Process for PDE4D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002027 regulation of heart rate ISS 16213210
GO:0006198 cAMP catabolic process IMP 19252089
GO:0006939 smooth muscle contraction IEA --
GO:0007165 signal transduction --
GO:0007568 aging IEA --
genes like me logo Genes that share ontologies with PDE4D: view

Compounds for PDE4D Gene

(5) Tocris Compounds for PDE4D Gene

Compound Action Cas Number
(R)-(-)-Rolipram PDE4 inhibitor. More active enantiomer of rolipram (Cat. No. 0905) [85416-75-7]
Cilostamide PDE3 inhibitor [68550-75-4]
IBMX PDE inhibitor (non-selective) [28822-58-4]
Rolipram PDE4 inhibitor [61413-54-5]
Sildenafil citrate Orally active, potent PDE5 inhibitor [171599-83-0]

(2) ApexBio Compounds for PDE4D Gene

Compound Action Cas Number
Apremilast (CC-10004) PDE4 inhibitor [608141-41-9]
Cilomilast Potent PDE4 inhibitor [153259-65-5]

(19) HMDB Compounds for PDE4D Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
Cyclic AMP
  • Cyclic AMP
Cyclic GMP
  • 3',5'-cyclic GMP
Guanosine monophosphate
  • 5'-GMP
  • Magnesium

(2) IUPHAR Ligand for PDE4D Gene

Ligand Type Action Affinity Pubmed IDs
rolipram Inhibitor Inhibition 7.2
Ro201724 Inhibitor Inhibition 6.2

(7) Novoseek inferred chemical compound relationships for PDE4D Gene

Compound -log(P) Hits PubMed IDs
rolipram 86.9 8
cilomilast 79.9 1
roflumilast 74.9 1
ibmx 54.6 1
forskolin 46.2 1

(1) PharmGKB related drug/compound annotations for PDE4D Gene

Drug/compound Annotation
diuretics CA
genes like me logo Genes that share compounds with PDE4D: view

Transcripts for PDE4D Gene

Unigene Clusters for PDE4D Gene

Phosphodiesterase 4D, cAMP-specific:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PDE4D

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PDE4D Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1: - - - - - - - - -
SP2: - - - - - - - -
SP3: - - - - - - - - - - - -
SP4: - - - - - - -
SP5: - - - - - -
SP6: -
SP7: -
SP9: - - - - -
SP11: - - - - - -

ExUns: 24a · 24b · 24c · 24d · 24e · 24f

Relevant External Links for PDE4D Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for PDE4D Gene

mRNA expression in normal human tissues for PDE4D Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PDE4D Gene

This gene is overexpressed in Muscle - Skeletal (10.6).

Protein differential expression in normal tissues for PDE4D Gene

This gene is overexpressed in Urinary Bladder (11.2), Fetal Brain (10.4), Brain (8.1), Lung (7.4), and Prostate (6.8).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for PDE4D Gene

SOURCE GeneReport for Unigene cluster for PDE4D Gene Hs.117545

mRNA Expression by UniProt/SwissProt for PDE4D Gene

Tissue specificity: Expressed in colonic epithelial cells (at protein level). Widespread; most abundant in skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney. Isoform 7 is detected in heart and skeletal muscle.
genes like me logo Genes that share expressions with PDE4D: view

Expression partners for PDE4D Gene

In Situ Assay Products

Orthologs for PDE4D Gene

This gene was present in the common ancestor of animals.

Orthologs for PDE4D Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia PDE4D 35
  • 92.16 (n)
  • 98.79 (a)
PDE4D 36
  • 93 (a)
(Canis familiaris)
Mammalia PDE4D 35
  • 93.42 (n)
  • 98.66 (a)
PDE4D 36
  • 97 (a)
(Pan troglodytes)
Mammalia PDE4D 35
  • 99.46 (n)
  • 99.46 (a)
PDE4D 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Pde4d 35
  • 90.23 (n)
  • 97.45 (a)
(Mus musculus)
Mammalia Pde4d 16
Pde4d 36
  • 88 (a)
(Monodelphis domestica)
Mammalia PDE4D 36
  • 95 (a)
(Ornithorhynchus anatinus)
Mammalia PDE4D 36
  • 93 (a)
(Gallus gallus)
Aves PDE4D 35
  • 84.86 (n)
  • 95.69 (a)
PDE4D 36
  • 96 (a)
(Anolis carolinensis)
Reptilia PDE4D 36
  • 91 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia pde4d 35
  • 82.15 (n)
  • 93.58 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.21705 35
(Danio rerio)
Actinopterygii pde4d 35
  • 75.16 (n)
  • 88.57 (a)
pde4d 36
  • 80 (a)
fruit fly
(Drosophila melanogaster)
Insecta dnc 37
  • 61 (a)
dnc 35
  • 60.14 (n)
  • 63.02 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000236 35
  • 56.72 (n)
  • 57.87 (a)
(Caenorhabditis elegans)
Secernentea R153.1a 37
  • 57 (a)
R153.1b 37
  • 57 (a)
pde-4 35
  • 55.97 (n)
  • 56.93 (a)
Species with no ortholog for PDE4D:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PDE4D Gene

Gene Tree for PDE4D (if available)
Gene Tree for PDE4D (if available)

Paralogs for PDE4D Gene

Paralogs for PDE4D Gene

genes like me logo Genes that share paralogs with PDE4D: view

Variants for PDE4D Gene

Sequence variations from dbSNP and Humsavar for PDE4D Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type MAF
rs1439 -- 59,202,714(+) GAGGA(A/G)GTCCC intron-variant
rs1960 -- 59,149,625(-) GGAAC(C/T)AACAC intron-variant
rs1961 -- 59,149,566(-) TCCAT(C/T)CCAGT intron-variant
rs26686 -- 59,296,854(-) TATGG(C/T)AGCTA intron-variant
rs26687 -- 59,245,564(-) TTTTC(A/G)AAAAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PDE4D Gene

Variant ID Type Subtype PubMed ID
nsv830312 CNV Gain 17160897
esv2730225 CNV Deletion 23290073
nsv830313 CNV Loss 17160897
esv2730226 CNV Deletion 23290073
esv1000440 CNV Deletion 20482838
esv1454268 CNV Deletion 17803354
esv2730227 CNV Deletion 23290073
esv2730229 CNV Deletion 23290073
esv2309169 CNV Deletion 18987734
esv2730230 CNV Deletion 23290073
esv2730231 CNV Deletion 23290073
esv1621306 CNV Deletion 17803354
nsv526881 CNV Gain 19592680
dgv343n21 CNV Loss 19592680
nsv881702 CNV Loss 21882294
nsv4846 CNV Insertion 18451855
nsv327785 CNV Loss 16902084
nsv328137 CNV Loss 16902084
esv2730232 CNV Deletion 23290073
esv268695 CNV Insertion 20981092
esv274312 CNV Insertion 20981092
nsv881703 CNV Loss 21882294
nsv520721 CNV Loss 19592680
nsv881704 CNV Loss 21882294
nsv881705 CNV Loss 21882294
nsv518845 CNV Loss 19592680
esv2730233 CNV Deletion 23290073
esv2730234 CNV Deletion 23290073
esv2730235 CNV Deletion 23290073
nsv881706 CNV Loss 21882294
nsv881707 CNV Loss 21882294
esv275451 CNV Loss 21479260
nsv881708 CNV Loss 21882294
nsv328623 CNV Loss 16902084
nsv462190 CNV Gain 19166990
esv2730236 CNV Deletion 23290073
nsv462191 CNV Loss 19166990
nsv328919 CNV Loss 16902084
nsv515987 CNV Loss 19592680
esv2672705 CNV Deletion 23128226
esv2671492 CNV Deletion 23128226
esv273089 CNV Insertion 20981092
dgv6075n71 CNV Loss 21882294
nsv508361 CNV Loss 20534489
esv2660953 CNV Deletion 23128226
nsv462192 CNV Loss 19166990
nsv830316 CNV Loss 17160897
esv2665396 CNV Deletion 23128226
esv21678 CNV Loss 19812545
esv32579 CNV Loss 17666407
esv2665058 CNV Deletion 23128226
nsv4847 CNV Loss 18451855
esv270152 CNV Insertion 20981092
esv274157 CNV Insertion 20981092
esv268638 CNV Insertion 20981092
nsv4848 CNV Insertion 18451855
esv2730237 CNV Deletion 23290073
esv272601 CNV Insertion 20981092
nsv4849 CNV Insertion 18451855
dgv705n27 CNV Gain 19166990
nsv516823 CNV Gain 19592680
nsv881711 CNV Gain 21882294
esv9436 CNV Gain 19470904

Relevant External Links for PDE4D Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PDE4D Gene

Disorders for PDE4D Gene

(2) OMIM Diseases for PDE4D Gene (600129)


  • Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.
  • Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems. {ECO:0000269 PubMed:22464250, ECO:0000269 PubMed:22464252, ECO:0000269 PubMed:23033274, ECO:0000269 PubMed:23043190}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for PDE4D Gene

(9) Novoseek inferred disease relationships for PDE4D Gene

Disease -log(P) Hits PubMed IDs
stroke 56.9 77
cerebral infarction 11 3
pulmonary disease chronic obstructive 9.66 1
respiratory disease 6.03 1
atherosclerosis 1.89 3

Relevant External Links for PDE4D

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with PDE4D: view

No data available for Genatlas for PDE4D Gene

Publications for PDE4D Gene

  1. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. (PMID: 14517540) Gretarsdottir S. … Gulcher J.R. (Nat. Genet. 2003) 3 4 23 48
  2. ALOX5AP gene and the PDE4D gene in a central European population of stroke patients. (PMID: 15731479) LA/hmussaar E. … Dichgans M. (Stroke 2005) 3 23 48
  3. Phosphodiesterase 4D gene, ischemic stroke, and asymptomatic carotid atherosclerosis. (PMID: 15802632) Bevan S. … Markus H.S. (Stroke 2005) 3 23 48
  4. Genotype and haplotype association study of the STRK1 region on 5q12 among Japanese: a case-control study. (PMID: 16322495) Nakayama T. … Soma M. (Stroke 2006) 3 23 48
  5. Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study. (PMID: 16373644) Woo D. … Broderick J. (Stroke 2006) 3 23 48

Products for PDE4D Gene

Sources for PDE4D Gene

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