Property Summary

NCBI Gene PubMed Count 80
PubMed Score 124.49
PubTator Score 119.84

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Type 2 diabetes mellitus 192 0.0 1.0
Disease Target Count Z-score Confidence
Acrodysostosis 9 3.653 1.8
Chronic obstructive pulmonary disease 147 3.442 1.7

Expression

  Differential Expression (33)

Disease log2 FC p
Bipolar Disorder 2.418 2.2e-02
gastric carcinoma 1.700 4.6e-02
Waldenstrons macroglobulinemia 1.116 1.9e-02
malignant mesothelioma -2.800 6.7e-07
oligodendroglioma 1.400 2.7e-02
osteosarcoma 1.890 5.4e-03
sonic hedgehog group medulloblastoma -2.700 1.5e-06
cystic fibrosis 2.093 3.2e-05
glioblastoma 1.400 3.5e-02
atypical teratoid/rhabdoid tumor -2.000 3.0e-04
medulloblastoma, large-cell -2.000 2.3e-05
acute quadriplegic myopathy 1.232 1.3e-02
tuberculosis -1.800 4.3e-04
lung cancer -2.800 4.5e-06
active Crohn's disease 1.387 3.1e-02
interstitial cystitis 2.500 5.4e-04
pilocytic astrocytoma 2.000 1.8e-05
posterior fossa group B ependymoma -1.100 6.6e-05
aldosterone-producing adenoma -1.077 2.0e-02
subependymal giant cell astrocytoma -1.424 4.9e-02
lung adenocarcinoma -1.411 1.1e-04
psoriasis -1.400 4.1e-06
Breast cancer -2.200 1.1e-05
invasive ductal carcinoma 1.800 2.6e-02
ulcerative colitis 4.000 7.6e-08
ovarian cancer 2.000 1.3e-04
Gaucher disease type 3 -2.100 1.7e-02
pituitary cancer 1.800 1.1e-02
Down syndrome 1.300 2.2e-03
chronic rhinosinusitis 1.006 3.5e-02
dermatomyositis 1.400 1.1e-02
head and neck cancer 1.200 4.8e-02
head and neck cancer and chronic obstruc... 1.300 3.4e-03

Synonym

Accession Q07343 A5YW33 O15443 Q13945 Q5TEK4 Q5TEK5 Q5TEK6
Symbols DPDE4
PDEIVB

Gene

PANTHER Protein Class (2)

PDB

2CHM   3HC8   3HDZ   1F0J   1JP1   1JP2   1RO6   1RO9   1ROR   1TB5   1XLX   1XLZ   1XM4   1XM6   1XMU   1XMY   1XN0   1XOS   1XOT   1Y2H   1Y2J   2QYL   3D3P   3FRG   3G45   3GWT   3HMV   3KKT   3LY2   3O0J   3O56   3O57   3W5E   3WD9   4KP6   4MYQ   4NW7   4WZI   4X0F  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
607 confirmatory 38 / 1666 / 7498 qHTS Assay for Inhibitors of PDE-IV

Gene RIF (50)

PMID Text
26756575 This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia.
26011935 Our results suggest that PDE4B does not play an important role during the chemotactic response of human neutrophils
25926551 Our results support previously reported association of PDE4B variations with schizophrenia in other populations.
25831493 analysis of the mechanism underlying synergistic up-regulation of PDE4B2 via a cross-talk between PKA-Cbeta and p65
24732776 Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity
23575688 ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4
23451206 PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for treatment of certain lymphoid diseases
22832604 Short Disrupted-in-Schizophrenia (DISC)1 splice variants show reduced or no binding to nudE nuclear distribution E homolog (NDEL)1 and PDE4B proteins but fully interact with fasciculation/elongation zeta (FEZ)1 and glycogen synthase kinase 3 GSK3beta.
22610099 PDE4B mediates ERK-dependent up-regulation of mucin MUC5AC by S. pneumoniae by inhibiting cAMP-PKA-dependent MKP-1 pathway.
22529021 PDE4B was downregulated and the protein kinase A pathway was activated in castration-resistant LNCaP prostate cancer cells. PDE4B expression was reduced in advanced prostate cancer and PDE4B knockdown promoted castration-resistant growth of LNCaP cells.
22160351 a study of Northwestern Han Chinese found that rs472952 is significantly associated with schizophrenia (SCZ) and rs7537440 is associated with SCZ in females; results provide further evidence that PDE4B may play important roles in the etiology of SCZ
21854221 The reported anti-inflammatory activity of bresol might be attributed to its abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes.
21742807 Overexpression of the PDE4B in diffuse large B-cell lymphoma (DLBCL) impinge on the same genes/pathways that are abnormally active in GC-resistant tumors.
21595828 Molecular dynamic simulations (with data from crystal structure of catalytic domain of PDE4B with cAMP bound) are used to investigate the catalytic mechanism of PDE4B in the hydrolysis of cAMP.
21520048 these data allow the assignment of different PDE4 subtypes to distinct functions of human lung fibroblasts and highlight the predominant role of PDE4B in controlling pathophysiological processes of human lung fibroblasts.
21184794 found a significant association between PDE4B and PD in the haplotype analysis. Sex-specific analyses demonstrated that PDE4B was associated with PD in females. results suggest PDE4B may play a role in the pathophysiology of PD in the Japanese population.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20436352 results do not support a genetic association between tardive dyskinesia and PDE4B
20436352 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20201926 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19834503 Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
19728060 phosphodiesterase 4B2 gene is an effector of Toll-like receptor signaling in astrocytes, and that its up-regulation at the protein level is controlled by complex mechanisms
19632097 There was no strong evidence for association with PDE4B in schizophrenia.
19632097 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
19506219 Observational study of gene-disease association. (HuGE Navigator)
19350560 Observational study of gene-disease association. (HuGE Navigator)
19251251 Observational study of gene-disease association. (HuGE Navigator)
19240061 Observational study of gene-disease association. (HuGE Navigator)
18983980 NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome.
18785206 the PDE4B gene itself does not link to major depressive disorder (MDD) but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD.
18785206 Observational study of gene-disease association. (HuGE Navigator)
18394866 the present observations suggest that dysregulation of intracellular signaling mediated by PDE4B is a significant factor in the cause and expression, respectively, of schizophrenia.
18394866 Observational study of gene-disease association. (HuGE Navigator)
18329668 Our result suggests that variations at the PDE4B locus may play a significant role in the etiology of SZ in the Japanese population.
18329668 Observational study of gene-disease association. (HuGE Navigator)
17823207 Altered DISC1-PDE4B interaction may thus underlie the symptoms of some cases of schizophrenia and depression.(Review)
17519386 A super-short, brain specific isoform of human PDE4B, PDE4B5, was identified. It has cAMP hydrolyzing activity and is inhibited by PDE4 inhibitors. PDE4B5 bind to DISC1. The 16 N-terminal residues are identical to the corresponding residues of PDE4D6.
17481393 Behavioral phenotypes of Disc1 missense mutations in mice and consequences for PDE4B
17417055 Observational study of gene-disease association. (HuGE Navigator)
17417055 PDE4B haplotype alters the genetic risk of schizophrenia in the Scottish population complements the known participation of this gene in biological processes associated with mental illness
17088426 Compartmentalized PDE4B acts as a sink to drain cAMP from discrete locations, resulting in multiple domains with different cAMP concentrations.
16997058 Reverse-transcription polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B, and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis.
16293762 a mechanistic model whereby DISC1 sequesters phosphodiesterase 4B in resting cells and releases it in an activated state in response to elevated cAMP
15331441 clinically relevant PDE4 and PI3K/AKT inhibitors might be useful in the treatment of Diffuse large B-cell lymphoma and additional B-lymphoid malignancies with increased PDE4B expression
14585965 TCR-dependent signaling activates PDE4B2 and enhances interleukin-2 production in T cells.
11839681 Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia
11156964 Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity
11114167 Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity

AA Sequence

MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQLPPLSQRQSERARTPEGDG      1 - 70
ISRPTTLPLTTLPSIAITTVSQECFDVENGPSPGRSPLDPQASSSAGLVLHATFPGHSQRRESFLYRSDS     71 - 140
DYDLSPKAMSRNSSLPSEQHGDDLIVTPFAQVLASLRSVRNNFTILTNLHGTSNKRSPAASQPPVSRVNP    141 - 210
QEESYQKLAMETLEELDWCLDQLETIQTYRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFL    211 - 280
DKQNDVEIPSPTQKDREKKKKQQLMTQISGVKKLMHSSSLNNTSISRFGVNTENEDHLAKELEDLNKWGL    281 - 350
NIFNVAGYSHNRPLTCIMYAIFQERDLLKTFRISSDTFITYMMTLEDHYHSDVAYHNSLHAADVAQSTHV    351 - 420
LLSTPALDAVFTDLEILAAIFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEE    421 - 490
HCDIFMNLTKKQRQTLRKMVIDMVLATDMSKHMSLLADLKTMVETKKVTSSGVLLLDNYTDRIQVLRNMV    491 - 560
HCADLSNPTKSLELYRQWTDRIMEEFFQQGDKERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETW    561 - 630
ADLVQPDAQDILDTLEDNRNWYQSMIPQSPSPPLDEQNRDCQGLMEKFQFELTLDEEDSEGPEKEGEGHS    631 - 700
YFSSTKTLCVIDPENRDSLGETDIDIATEDKSPVDT                                      701 - 736
//

Text Mined References (83)

PMID Year Title
26756575 2016 Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies.
26011935 2015 The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor.
25926551 2015 Association analysis of PDE4B polymorphisms with schizophrenia and smooth pursuit eye movement abnormality in a Korean population.
25831493 2015 Cross-talk between PKA-C? and p65 mediates synergistic induction of PDE4B by roflumilast and NTHi.
24847357 2014 Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections.
24722188 2014 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
23575688 2013 Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD.
23451206 2013 Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
23007406 2012 Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia.
22832604 2011 Interactions of human truncated DISC1 proteins: implications for schizophrenia.
22610099 2012 Phosphodiesterase 4B mediates extracellular signal-regulated kinase-dependent up-regulation of mucin MUC5AC protein by Streptococcus pneumoniae by inhibiting cAMP-protein kinase A-dependent MKP-1 phosphatase pathway.
22566634 2012 The genetic architecture of economic and political preferences.
22529021 2012 Downregulation of phosphodiesterase 4B (PDE4B) activates protein kinase A and contributes to the progression of prostate cancer.
22384243 2012 ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2.
22160351 2012 Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese.
22076464 2012 Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.
21854221 Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of select mediators of inflammation in human monocytic cells.
21742807 2011 Gene set enrichment analysis unveils the mechanism for the phosphodiesterase 4B control of glucocorticoid response in B-cell lymphoma.
21595828 2011 Insight into the phosphodiesterase mechanism from combined QM/MM free energy simulations.
21520048 2011 The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion.
21358715 2011 Co-ordinated action of DISC1, PDE4B and GSK3? in modulation of cAMP signalling.
21184794 2011 Association study of PDE4B with panic disorder in the Japanese population.
21047676 2010 Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma.
20701803 2010 An evolutionary analysis of cAMP-specific Phosphodiesterase 4 alternative splicing.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20436352 2010 Phosphodiesterase 4B genetic variants are not associated with antipsychotic-induced tardive dyskinesia.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20347962 2010 The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D.
20201926 2010 Human variation in alcohol response is influenced by variation in neuronal signaling genes.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19834503 2009 Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
19728060 2009 Phosphodiesterase 4B2 gene is an effector of Toll-like receptor signaling in astrocytes.
19632097 2009 Genetic association and post-mortem brain mRNA analysis of DISC1 and related genes in schizophrenia.
19506219 2009 Risk alleles for multiple sclerosis in multiplex families.
19350560 2010 Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples.
19251251 2009 Association between genes of Disrupted in schizophrenia 1 (DISC1) interactors and schizophrenia supports the role of the DISC1 pathway in the etiology of major mental illnesses.
19240061 2009 Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.
19060910 2009 Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
18983980 2008 DISC1, PDE4B, and NDE1 at the centrosome and synapse.
18785206 2009 Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population.
18687753 2008 Enhanced PDE4B expression augments LPS-inducible TNF expression in ethanol-primed monocytes: relevance to alcoholic liver disease.
18539455 2008 Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors.
18394866 2008 PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia.
18329668 2008 Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the Japanese population.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17903301 2007 Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study.
17823207 2007 Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illness.
17728464 2007 Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels.
17727341 2007 Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors.
17519386 2007 PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 variant whose isoform-specifying N-terminal region is identical to that of cAMP phosphodiesterase-4D6 (PDE4D6).
17481393 2007 Behavioral phenotypes of Disc1 missense mutations in mice.
17417055 2007 The PDE4B gene confers sex-specific protection against schizophrenia.
17404263 2007 Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4+ T cells: predominant role of PDE4D.
17088426 2006 PGE(1) stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases.
16997058 2006 Hemodialysis modulates gene expression profile in skeletal muscle.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16293762 2005 DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling.
15685167 2005 A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design.
15576036 2004 Structural basis for the activity of drugs that inhibit phosphodiesterases.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15331441 2005 The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma.
15260978 2004 A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases.
15146197 2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.
15003452 2004 Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14585965 2003 Regulation of T-cell activation by phosphodiesterase 4B2 requires its dynamic redistribution during immunological synapse formation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12441002 2003 Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform.
12032334 2002 Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses.
11839681 2002 Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia.
11468344 2001 Identification of overlapping but distinct cAMP and cGMP interaction sites with cyclic nucleotide phosphodiesterase 3A by site-directed mutagenesis and molecular modeling based on crystalline PDE4B.
11114167 2000 Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication.
10846163 2000 Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity.
10385698 1999 Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils.
9882697 1999 Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes.
9371714 1997 Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3.
8413254 1993 A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs.
8392015 1993 The cDNA of a human lymphocyte cyclic-AMP phosphodiesterase (PDE IV) reveals a multigene family.
8384210 1993 A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA.
8009369 1994 Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse.
7958996 1994 Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases.
7835077 1995 Chromosomal localization of the human and rat genes (PDE4D and PDE4B) encoding the cAMP-specific phosphodiesterases 3 and 4.