PDE3A Gene

HGNC Family	Phosphodiesterases (PDE)
Name	phosphodiesterase 3A, cGMP-inhibited
Description	This gene encodes a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes hydrolyze both cAMP and cGMP, and play critical roles in many cellular processes by regulating the amplitude and duration of intracellular cyclic nucleotide signals. The encoded protein mediates platelet aggregation and also plays important roles in cardiovascular function by regulating vascular smooth muscle contraction and relaxation. Inhibitors of the encoded protein may be effective in treating congestive heart failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhosphodiesterase 3A (PDE3A) is a key regulator of cyclic nucleotide signaling in the heart and vascular smooth muscle. In cardiac myocytes, multiple PDE3A isoforms—with distinct N‐terminal domains—mediate cAMP and cGMP hydrolysis, thereby controlling contractile function and regional intracellular signaling. Studies demonstrate that PDE3A expression is modulated by pathophysiological stress (for example, chronic hypoxia and dilated cardiomyopathy) and post‐translational modifications such as PKA phosphorylation and interactions with scaffolding proteins (e.g., CFTR, SERCA2, and AKAP18) that dictate its compartmentalized activity. Moreover, PDE3A can hydrolyze additional cyclic nucleotides such as cUMP and its interaction with regulatory proteins is emerging as an important mechanism for fine‐tuning cardiac performance. These data collectively point to an essential role for PDE3A in modulating myocardial contractility and vascular tone under both normal and diseased conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn platelets and vascular smooth muscle cells, PDE3A activity critically governs cellular cAMP levels and thereby modulates processes such as platelet aggregation, Ca²⁺ mobilization, and smooth muscle proliferation. Pharmacological inhibition of PDE3A attenuates thrombin‐ and PKC–mediated phosphorylation events that stimulate cAMP degradation, which in turn maintains or restores inhibitory cyclic nucleotide pools. Notably, gain‐of‐function mutations in PDE3A have been linked to phenotypes such as hypertension with brachydactyly—syndromes marked by enhanced cAMP hydrolytic activity and aberrant vascular cell proliferation—and associations with altered serum lipid profiles and inflammatory responses further underscore a role for PDE3A in cardiovascular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its cardiovascular roles, PDE3A contributes to diverse biological processes including reproductive cell maturation and cancer biology. Its mRNA is expressed in human germinal vesicle–stage oocytes where selective inhibition arrests meiotic progression, highlighting a regulatory function in oocyte maturation. In cancer cells, emerging evidence indicates that PDE3A levels not only serve as a predictive biomarker for sensitivity to selective PDE inhibitors but also participate in oncogenic signaling; for example, the formation of a multi‐protein complex between PDE3A and SLFN12 has been implicated in increasing RNase activity, which in turn modulates cancer cell proliferation and metastatic potential. Moreover, altered PDE3A expression has been observed in chemoresistant tumors, underscoring its potential as a therapeutic target in oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeremy Wechsler, Young-Hun Choi, Judith Krall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203647200"}], "href": "https://doi.org/10.1074/jbc.M203647200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12154085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12154085"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fiona Murray, Margaret R MacLean, Nigel J Pyne "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of the cGMP-inhibited cAMP-specific (PDE3) and cGMP binding cGMP-specific (PDE5) phosphodiesterases in models of pulmonary hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjp.0704984"}], "href": "https://doi.org/10.1038/sj.bjp.0704984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12466227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12466227"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryan Hambleton, Judith Krall, Eliso Tikishvili, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Phosphodiesterase 3A rs7134375 single nucleotide polymorphism and serum lipid levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2014.2007"}], "href": "https://doi.org/10.3892/mmr.2014.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24604378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24604378"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "A Julià, C Ferrándiz, E Dauden, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PDE3A mutations cause autosomal dominant hypertension with brachydactyly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3302"}], "href": "https://doi.org/10.1038/ng.3302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25961942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25961942"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Hiroko Boda, Hidetoshi Uchida, Nobue Takaiso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A PDE3A mutation in familial hypertension and brachydactyly syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2016.32"}], "href": "https://doi.org/10.1038/jhg.2016.32"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27053290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27053290"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Daniela Nogueira, Carola Albano, Tom Adriaenssens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.103.015982"}], "href": "https://doi.org/10.1095/biolreprod.103.015982"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12773402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12773402"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "F-M Tian, C-Y Zhong, X-N Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDE3A is hypermethylated in cisplatin resistant non-small cell lung cancer cells and is a modulator of chemotherapy response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2017)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28678321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28678321"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Madiha Nazir, Wojciech Senkowski, Frida Nyberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting tumor cells based on Phosphodiesterase 3A expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2017.10.032"}], "href": "https://doi.org/10.1016/j.yexcr.2017.10.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29107068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29107068"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Na Hao, Wenzhi Shen, Renle Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphodiesterase 3A Represents a Therapeutic Target that Drives Stem Cell-like Property and Metastasis in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-18-1233"}], "href": "https://doi.org/10.1158/1535-7163.MCT-18-1233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31871268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31871268"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "You Ran Kim, MyeongJin Yi, Sun-Ah Cho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ahg.12411"}], "href": "https://doi.org/10.1111/ahg.12411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33249558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33249558"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Colin W Garvie, Xiaoyun Wu, Malvina Papanastasiou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-24495-w"}], "href": "https://doi.org/10.1038/s41467-021-24495-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34272366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34272366"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Chia-Ying Yeh, Huei Yu Cai, Han-His Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALDOA coordinates PDE3A through the β-catenin/ID3 axis to stimulate cancer metastasis and M2 polarization in lung cancer with EGFR mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2024.149489"}], "href": "https://doi.org/10.1016/j.bbrc.2024.149489"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38244313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38244313"}]}]}]}
Synonyms	CGI-PDE-A, CGI-PDE, HTNB, CGI-PDE A
Proteins	PDE3A_HUMAN
NCBI Gene ID	5139
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PDE3A has 7,769 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 135 datasets.

Click the + buttons to view associations for PDE3A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PDE3A Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PDE3A gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PDE3A 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 PDE3A 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 PDE3A 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 PDE3A 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 PDE3A 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 PDE3A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving PDE3A protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PDE3A 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 PDE3A 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 PDE3A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PDE3A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDE3A 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 PDE3A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PDE3A 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 PDE3A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PDE3A 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 PDE3A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PDE3A gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PDE3A gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PDE3A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PDE3A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PDE3A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PDE3A 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 PDE3A 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 PDE3A 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 PDE3A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PDE3A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PDE3A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PDE3A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PDE3A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PDE3A gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PDE3A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for PDE3A protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PDE3A 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 PDE3A 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 PDE3A 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 PDE3A 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 PDE3A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PDE3A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.