PDE6D Gene

HGNC Family	Phosphodiesterases (PDE)
Name	phosphodiesterase 6D, cGMP-specific, rod, delta
Description	This gene encodes the delta subunit of rod-specific photoreceptor phosphodiesterase (PDE), a key enzyme in the phototransduction cascade. A similar protein in cow functions in solubilizing membrane-bound PDE. In addition to its role in the PDE complex, the encoded protein is thought to bind to prenyl groups of proteins to target them to subcellular organelles called cilia. Mutations in this gene are associated with Joubert syndrome-22. Alternative splicing results in multiple splice variants. [provided by RefSeq, Mar 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhosphodiesterase 6D (PDE6D) functions as a prenyl‐binding chaperone that facilitates the solubilization and intracellular trafficking of farnesylated proteins. Notably, PDE6D’s GDI‐like pocket binds to the prenyl moieties of Ras family GTPases, thereby enhancing their diffusion in the cytoplasm and ensuring their proper enrichment at the plasma membrane for effective signal transduction. This activity is critical for maintaining the dynamic spatial distribution of Ras proteins that underlies regulated and oncogenic Ras signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to modulating Ras signaling, PDE6D plays a pivotal role in the trafficking of prenylated proteins to the primary cilium. It functions as an essential mediator for the ciliary targeting of INPP5E, a prenylated inositol polyphosphate-5-phosphatase implicated in ciliopathies such as Joubert syndrome. PDE6D-dependent delivery of INPP5E, which is facilitated by additional ciliary factors like ARL13B and the cargo-release regulator ARL3, ensures that prenylated proteins reach the ciliary compartment where they participate in signaling and structural functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPDE6D is also integral to the maintenance of photoreceptor integrity. By associating with the ciliary protein RPGR, PDE6D engages in the trafficking of farnesylated cargo necessary for the function of the photoreceptor outer segment. Disruption of this interaction has been linked to retinal degeneration and highlights the crucial role of PDE6D in the specialized transport processes in the retina."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established roles in ciliary biology and Ras signaling, PDE6D has emerged as a potential therapeutic target in RAS‐mutated cancers. Recent evidence indicates that small molecules binding to the hydrophobic pocket of PDE6D can disrupt the proper localization of RAS proteins, thereby impairing downstream RAC activation and affecting leukemic cell survival. This finding underscores PDE6D’s importance in the regulation of oncogenic pathways and its potential as a drug target in high‐risk leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, advanced proteomic analyses have broadened our understanding of PDE6D’s cargo repertoire by revealing additional prenylated proteins that depend on PDE6D for their ciliary localization. These studies not only consolidate the role of PDE6D in ciliary protein sorting but also further link its dysfunction to ciliopathies such as Joubert syndrome, thereby emphasizing the clinical importance of prenyl‐binding–dependent trafficking mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anchal Chandra, Hernán E Grecco, Venkat Pisupati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2394"}], "href": "https://doi.org/10.1038/ncb2394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22179043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22179043"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Melissa C Humbert, Katie Weihbrecht, Charles C Searby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1210916109"}], "href": "https://doi.org/10.1073/pnas.1210916109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23150559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23150559"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sophie Thomas, Kevin J Wright, Stéphanie Le Corre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22470"}], "href": "https://doi.org/10.1002/humu.22470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24166846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24166846"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Denise Wätzlich, Ingrid Vetter, Katja Gotthardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/embor.2013.37"}], "href": "https://doi.org/10.1038/embor.2013.37"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23559067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23559067"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kollu N Rao, Wei Zhang, Linjing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prenylated retinal ciliopathy protein RPGR interacts with PDE6δ and regulates ciliary localization of Joubert syndrome-associated protein INPP5E."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw281"}], "href": "https://doi.org/10.1093/hmg/ddw281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28172980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28172980"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sara Canovas Nunes, Serena De Vita, Andrew Anighoro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cancer J (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41408-022-00663-z"}], "href": "https://doi.org/10.1038/s41408-022-00663-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35422065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35422065"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Siebren Faber, Stef J F Letteboer, Katrin Junger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells12020312"}], "href": "https://doi.org/10.3390/cells12020312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36672247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36672247"}]}]}]}
Synonyms	JBTS22, PDED
Proteins	PDE6D_HUMAN
NCBI Gene ID	5147
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PDE6D has 5,613 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for PDE6D from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PDE6D 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 PDE6D 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 PDE6D 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 PDE6D gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PDE6D 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 PDE6D 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 PDE6D 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 PDE6D 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 PDE6D 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 PDE6D 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 PDE6D 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 PDE6D gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PDE6D protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PDE6D 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 PDE6D gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PDE6D 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 PDE6D gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PDE6D gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PDE6D gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PDE6D protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PDE6D protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PDE6D 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 PDE6D 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 PDE6D gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PDE6D gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PDE6D gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PDE6D gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PDE6D 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 PDE6D gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PDE6D gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PDE6D 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 PDE6D 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 PDE6D 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 PDE6D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PDE6D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PDE6D 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 PDE6D gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PDE6D gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PDE6D from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PDE6D gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PDE6D gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.