PDE8A Gene

HGNC Family	Phosphodiesterases (PDE)
Name	phosphodiesterase 8A
Description	The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhosphodiesterase 8A (PDE8A) is a highly specific, cAMP‐degrading enzyme whose catalytic properties have been elucidated at the structural and kinetic levels. Detailed studies of the PDE8A₁ catalytic domain have shown that its substrate specificity is governed by low Kₘ values for cAMP and that unique structural elements—such as extra helical regions—can modulate its sensitivity to inhibitors. Moreover, PDE8A activity is dynamically regulated by direct post‐translational modifications; for instance, under elevated cAMP conditions, protein kinase A (PKA) phosphorylates PDE8A on serine 359, thereby enhancing its catalytic function in a feedback mechanism. In addition, interactions mediated by its PAS domain, including binding to IkappaB family members, further potentiate its activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPDE8A also plays a critical role in orchestrating intracellular signaling cascades by modulating local cAMP levels. It associates with key signaling molecules, such as Raf‐1, protecting this kinase from PKA‐mediated inhibitory phosphorylation and thereby promoting effective ERK/MAPK pathway activation. In certain cellular compartments—exemplified by its localization within lipid rafts of airway smooth muscle cells—PDE8A is strategically positioned to selectively regulate signaling complexes, such as the beta₂-adrenergic receptor–AC6 module. Furthermore, interaction with regulatory proteins like 14-3-3ζ can attenuate PDE8A’s catalytic activity, thereby influencing the balance between cAMP/PKA and MAPK pathway activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPhysiologically, PDE8A has emerged as a significant modulator across diverse tissues and in various disease contexts. Variations in PDE8A expression and genetic polymorphisms are linked to altered outcomes in infectious and neuropsychiatric disorders; for example, lower PDE8A levels in macrophages correlate with reduced HIV-1 replication, while changes in its RNA editing profile have been associated with major depressive disorder and suicide. In addition, PDE8A has been implicated in regulating key processes in the airways—such as modulating CFTR activity—and is expressed during specific stages of spermatogenesis, suggesting roles in reproductive cell differentiation. Although investigation in steroidogenic cell types, including in the context of polycystic ovary syndrome, has not established a dominant role for PDE8A, these findings collectively underscore its importance as a finely tuned regulator of cAMP-mediated signaling in both health and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huanchen Wang, Zier Yan, Serena Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi801487x"}], "href": "https://doi.org/10.1021/bi801487x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18983167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18983167"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michiko Gamanuma, Keizo Yuasa, Takashi Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0898-6568(02)00146-8"}], "href": "https://doi.org/10.1016/s0898-6568(02"}, {"type": "t", "text": "00146-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12681444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12681444"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kim M Brown, Louisa C Y Lee, Jane E Findlay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2012.04.033"}], "href": "https://doi.org/10.1016/j.febslet.2012.04.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22673573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22673573"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ping Wu, Peng Wang "}, {"type": "b", "children": [{"type": "t", "text": "Per-Arnt-Sim domain-dependent association of cAMP-phosphodiesterase 8A1 with IkappaB proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0407649101"}], "href": "https://doi.org/10.1073/pnas.0407649101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15596729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15596729"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kim M Brown, Jon P Day, Elaine Huston, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphodiesterase-8A binds to and regulates Raf-1 kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1303004110"}], "href": "https://doi.org/10.1073/pnas.1303004110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23509299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23509299"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Timothy B Johnstone, Kaitlyn H Smith, Cynthia J Koziol-White, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by β"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "-Adrenergic Receptors and Adenylyl Cyclase 6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2017-0294OC"}], "href": "https://doi.org/10.1165/rcmb.2017-0294OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29262264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29262264"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hanan Qasim, Mehrdad Rajaei, Ying Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AKAP12 Upregulation Associates With PDE8A to Accelerate Cardiac Dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.123.323655"}], "href": "https://doi.org/10.1161/CIRCRESAHA.123.323655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38506047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38506047"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chen Chen, Jessica Wickenheisser, Kathryn G Ewens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDE8A genetic variation, polycystic ovary syndrome and androgen levels in women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gap035"}], "href": "https://doi.org/10.1093/molehr/gap035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19482904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19482904"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sebastiaan M Bol, Thijs Booiman, Evelien M Bunnik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.virol.2011.08.013"}], "href": "https://doi.org/10.1016/j.virol.2011.08.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21920574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21920574"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Srinath Krishnamurthy, Balakrishnan Shenbaga Moorthy, Lim Xin Xiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biophys J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bpj.2014.07.050"}], "href": "https://doi.org/10.1016/j.bpj.2014.07.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25229150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25229150"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nicolas Salvetat, Fabrice Chimienti, Christopher Cayzac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41398-021-01377-9"}], "href": "https://doi.org/10.1038/s41398-021-01377-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33931591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33931591"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Mark J Turner, Yukiko Sato, David Y Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphodiesterase 8A Regulates CFTR Activity in Airway Epithelial Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.33594/000000477"}], "href": "https://doi.org/10.33594/000000477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34936285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34936285"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Federica Campolo, Chiara Capponi, Maria Grazia Tarsitano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Endocrinol (Lausanne) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fendo.2022.1010924"}], "href": "https://doi.org/10.3389/fendo.2022.1010924"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36277728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36277728"}]}]}]}
Synonyms	HST19550
Proteins	PDE8A_HUMAN
NCBI Gene ID	5151
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PDE8A has 8,939 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

Click the + buttons to view associations for PDE8A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PDE8A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PDE8A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PDE8A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PDE8A gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PDE8A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PDE8A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PDE8A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PDE8A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PDE8A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PDE8A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDE8A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PDE8A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PDE8A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PDE8A gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PDE8A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PDE8A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PDE8A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PDE8A protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PDE8A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PDE8A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PDE8A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PDE8A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PDE8A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PDE8A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PDE8A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PDE8A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PDE8A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PDE8A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PDE8A gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PDE8A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PDE8A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PDE8A gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PDE8A gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PDE8A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PDE8A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PDE8A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PDE8A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PDE8A protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PDE8A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PDE8A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PDE8A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.