Details for: PDE6G

Gene ID: 5148

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PDE6G

Ensembl ID: ENSG00000185527

Description: phosphodiesterase 6G

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal rod cell CL0000604
    CSI 42.5
    rCSI 74.91%
    PRS 97.57
  • regulatory T cell CL0000815
    CSI 33.86
    rCSI 39.26%
    PRS 95.34
  • chondrocyte CL0000138
    CSI 33.55
    rCSI 53.35%
    PRS 97.78
  • pericyte CL0000669
    CSI 28.9
    rCSI 76.97%
    PRS 89.81
  • basal cell of epidermis CL0002187
    CSI 27.31
    rCSI 48.4%
    PRS 86.77
  • helper T cell CL0000912
    CSI 27.19
    rCSI 38.44%
    PRS 96.21
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 26.28
    rCSI 31.84%
    PRS 90.32
  • melanocyte of skin CL1000458
    CSI 25.03
    rCSI 34.11%
    PRS 88.06
  • mast cell CL0000097
    CSI 23.4
    rCSI 50.52%
    PRS 94.48
  • suprabasal keratinocyte CL4033013
    CSI 21.83
    rCSI 35.64%
    PRS 88.58
  • ON-bipolar cell CL0000749
    CSI 20.9
    rCSI 31.06%
    PRS 98.13
  • early lymphoid progenitor CL0000936
    CSI 20.25
    rCSI 17.78%
    PRS 99.46
  • hematopoietic stem cell CL0000037
    CSI 19.95
    rCSI 13.26%
    PRS 99.37
  • Mueller cell CL0000636
    CSI 18.05
    rCSI 41.19%
    PRS 97.47
  • rod bipolar cell CL0000751
    CSI 15.79
    rCSI 28.37%
    PRS 97.54
  • OFF-bipolar cell CL0000750
    CSI 15.78
    rCSI 21.58%
    PRS 98.05
  • retinal pigment epithelial cell CL0002586
    CSI 10.67
    rCSI 21.19%
    PRS 97.95
  • group 3 innate lymphoid cell CL0001071
    CSI 10.54
    rCSI 7.92%
    PRS 99.37
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 10.04
    rCSI 9.07%
    PRS 99.11
  • retina horizontal cell CL0000745
    CSI 9.41
    rCSI 14.34%
    PRS 98.09
  • glial cell CL0000125
    CSI 8.24
    rCSI 31.39%
    PRS 96.84
  • neural progenitor cell CL0011020
    CSI 8.22
    rCSI 36.15%
    PRS 94.81
  • retinal cone cell CL0000573
    CSI 8.08
    rCSI 13.01%
    PRS 96.83
  • innate lymphoid cell CL0001065
    CSI 8
    rCSI 16.53%
    PRS 95.85
  • retinal bipolar neuron CL0000748
    CSI 8
    rCSI 14.98%
    PRS 96.97
  • glycinergic amacrine cell CL4030028
    CSI 6.1
    rCSI 15.88%
    PRS 96.26
  • amacrine cell CL0000561
    CSI 5.74
    rCSI 16.64%
    PRS 96.61
  • cytotoxic T cell CL0000910
    CSI 4.48
    rCSI 25.65%
    PRS 96.74
  • type EC enteroendocrine cell CL0000577
    CSI 4.47
    rCSI 15.85%
    PRS 98.8
  • retinal ganglion cell CL0000740
    CSI 3.13
    rCSI 6.91%
    PRS 96.54
  • conventional dendritic cell CL0000990
    CSI 2.56
    rCSI 2.14%
    PRS 95.26
  • GABAergic amacrine cell CL4030027
    CSI 1.88
    rCSI 6.44%
    PRS 94.57
  • group 2 innate lymphoid cell CL0001069
    CSI 1.53
    rCSI 8.28%
    PRS 99.41

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PDE6G](/details-gene/5148) encodes the gamma subunit of the rod-specific cGMP phosphodiesterase, a critical enzyme in the visual phototransduction cascade. Its primary and best-characterized function is to act as an inhibitory subunit that, upon activation by transducin, allows the catalytic breakdown of cGMP, leading to the closure of cation channels in photoreceptor cells and subsequent neural signaling. This is strongly supported by its exceptionally high expression in [retinal rod cells](/details-cell/CL0000604). Mutations in this gene are clinically associated with autosomal recessive retinitis pigmentosa ([180073](https://omim.org/entry/180073)), a degenerative eye disease, as documented in several studies ([Link](https://doi.org/10.1016/j.ajhg.2010.06.016)). Intriguingly, expression data also reveals significant expression in a diverse range of non-retinal cell types, including various T-cell subsets, [chondrocytes](/details-cell/CL0000138), and epidermal cells, suggesting that [PDE6G](/details-gene/5148) may have broader, less-understood roles in regulating cGMP-mediated signaling in the immune system and other tissues. ## Cellular Roles and Expression Landscape The expression profile of [PDE6G](/details-gene/5148) confirms its central role in retinal biology while simultaneously highlighting its potential involvement in other physiological systems. **Overall**, the gene's highest significance is observed in the [retinal rod cell](/details-cell/CL0000604) (CSI: 42.50), consistent with its canonical function in vision. Significant expression is also noted in other retinal cell types such as the [ON-bipolar cell](/details-cell/CL0000749), [Mueller cell](/details-cell/CL0000636), and [rod bipolar cell](/details-cell/CL0000751), underscoring its deep integration within the retinal cellular network. Beyond the retina, [PDE6G](/details-gene/5148) demonstrates a notable presence in the immune system. It is highly significant in [regulatory T cells](/details-cell/CL0000815) (CSI: 33.86), [helper T cells](/details-cell/CL0000912), and [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203). Its expression in [early lymphoid progenitors](/details-cell/CL0000936) and [hematopoietic stem cells](/details-cell/CL0000037) suggests a potential role starting from early stages of hematopoiesis. Furthermore, a distinct expression signature is evident in structural and epithelial tissues. High significance scores in [chondrocytes](/details-cell/CL0000138) (CSI: 33.55) and [pericytes](/details-cell/CL0000669) point towards a possible function in connective tissue and vascular homeostasis. A similar pattern is observed in the skin, with significant expression in [basal cell of epidermis](/details-cell/CL0002187), [melanocyte of skin](/details-cell/CL1000458), and [suprabasal keratinocyte](/details-cell/CL4033013), suggesting a role in epidermal maintenance or signaling. ## Pathways and Molecular Function The functional annotations for [PDE6G](/details-gene/5148) align well with its cellular expression profile. Its molecular function is defined by its role as an '[enzyme inhibitor activity](/details-go/GO0004857)' that modulates '[calmodulin-activated 3',5'-cyclic-gmp phosphodiesterase activity](/details-go/GO0048101)'. This is the central mechanism for its function in the retina. The gene's involvement is most prominent in pathways related to vision, including '[The phototransduction cascade](/details-reactome/R-HSA-2514856)' ([R-HSA-2514856](https://reactome.org/content/detail/R-HSA-2514856)) and '[Visual perception](/details-go/GO0007601)' ([GO:0007601](https://www.ebi.ac.uk/QuickGO/term/GO:0007601)). Its localization to the '[photoreceptor outer segment membrane](/details-go/GO0042622)' ([GO:0042622](https://www.ebi.ac.uk/QuickGO/term/GO:0042622)) is critical for this process. The broader signaling pathways annotated for [PDE6G](/details-gene/5148) may explain its role in non-retinal cells. Its participation in the '[Ca2+ pathway](/details-reactome/R-HSA-4086398)' ([R-HSA-4086398](https://reactome.org/content/detail/R-HSA-4086398)), '[positive regulation of mapk cascade](/details-go/GO0043410)' ([GO:0043410](https://www.ebi.ac.uk/QuickGO/term/GO:0043410)), and '[Signaling by wnt](/details-reactome/R-HSA-195721)' ([R-HSA-195721](https://reactome.org/content/detail/R-HSA-195721)) provides a molecular basis for its potential functions in T-cell signaling, chondrocyte homeostasis, and epidermal cell regulation, where these pathways are known to be active. ## Research Directions While the role of [PDE6G](/details-gene/5148) in vision is well-established, its significant expression in other tissues, particularly the immune system, opens up new avenues for investigation. The data suggests that its function extends beyond phototransduction, likely as a key regulator of cGMP signaling in diverse cellular contexts. **Testable Hypotheses:** 1. **Immunomodulation via cGMP Regulation:** The high significance of [PDE6G](/details-gene/5148) in [regulatory T cells](/details-cell/CL0000815) suggests it is a key regulator of their suppressive function. By hydrolyzing cGMP, [PDE6G](/details-gene/5148) may maintain a specific intracellular signaling environment required for Treg lineage stability and inhibitory activity, potentially by dampening proliferative signals. 2. **Role in Cartilage Biology:** The prominent expression in [chondrocytes](/details-cell/CL0000138) indicates a potential role for [PDE6G](/details-gene/5148) in cartilage homeostasis. It may modulate chondrocyte response to growth factors or mechanical stress by controlling cGMP levels, thereby influencing the synthesis of extracellular matrix components and contributing to the maintenance of cartilage integrity. **Proposed Experiment:** To test the hypothesis regarding its role in [regulatory T cells](/details-cell/CL0000815), a functional genomics approach could be employed. Primary human CD4+ T cells could be isolated, and [PDE6G](/details-gene/5148) expression could be knocked down using shRNA or knocked out via CRISPR-Cas9. These modified cells would then be differentiated into induced Tregs (iTregs) in vitro. The functional consequences would be assessed by measuring changes in intracellular cGMP levels via ELISA, analyzing the expression of key Treg markers (e.g., FOXP3, CTLA-4) by flow cytometry, and evaluating their suppressive capacity in co-culture assays with effector T cells. **Therapeutic Potential:** The primary therapeutic relevance of [PDE6G](/details-gene/5148) is in treating autosomal recessive retinitis pigmentosa, a loss-of-function disorder ([Link](https://doi.org/10.1016/j.ajhg.2010.06.016)). Consequently, therapeutic strategies would focus on **activation** or gene replacement, such as AAV-mediated gene therapy, to restore protein function in retinal cells. The potential for targeting [PDE6G](/details-gene/5148) in other contexts, such as autoimmune disease, is speculative but intriguing. The development of specific inhibitors could increase cGMP levels in T cells, potentially augmenting anti-tumor immunity, while specific activators could enhance Treg function to treat autoimmunity. However, achieving cell-type specificity would be a major challenge for any small-molecule approach.

Genular Protein ID: 2776398939

Symbol: CNRG_HUMAN

Name: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

UniProtKB Accession Codes:

P18545 Q3KP63 Q7Z3U8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 4 ChEMBL 2 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 4 DrugCentral 1 EC 2 EMBL 7 Ensembl 3 EvolutionaryTrace 1 GO 11 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 4 Rhea 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2161380

Title: Isolation and characterization of cDNA encoding the gamma-subunit of cGMP phosphodiesterase in human retina.

PubMed ID: 2161380

DOI: 10.1016/0378-1119(90)90035-p

PubMed ID: 1965799

Title: The organization of the gamma-subunit gene of human photoreceptor cyclic GMP phosphodiesterase.

PubMed ID: 1965799

PubMed ID: 8125719

Title: Evaluation of the gene encoding the gamma subunit of rod phosphodiesterase in retinitis pigmentosa.

PubMed ID: 8125719

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 20655036

Title: Autosomal-recessive early-onset retinitis pigmentosa caused by a mutation in PDE6G, the gene encoding the gamma subunit of rod cGMP phosphodiesterase.

PubMed ID: 20655036

DOI: 10.1016/j.ajhg.2010.06.016

Sequence Information:

  • Length: 87
  • Mass: 9643
  • Checksum: 5D7DEE59D7DDB9E0
  • Sequence:
    • MNLEPPKAEF RSATRVAGGP VTPRKGPPKF KQRQTRQFKS KPPKKGVQGF GDDIPGMEGL 
GTDITVICPW EAFNHLELHE LAQYGII