Details for: PDE6B

Gene ID: 5158

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: PDE6B

Ensembl ID: ENSG00000133256

Description: phosphodiesterase 6B

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 19.29
    rCSI 34%
    PRS 92.32
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 6.41
    rCSI 7.97%
    PRS 85.5
  • S cone cell CL0003050
    CSI 4.7
    rCSI 20.65%
    PRS 91.8
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 3.69
    rCSI 8.97%
    PRS 85.53
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.2
    rCSI 11.5%
    PRS 85.81
  • hematopoietic stem cell CL0000037
    CSI 2.65
    rCSI 1.76%
    PRS 96.18
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.53
    rCSI 2.28%
    PRS 94.67
  • retinal bipolar neuron CL0000748
    CSI 2.46
    rCSI 4.61%
    PRS 89.89
  • ciliated epithelial cell CL0000067
    CSI 2.27
    rCSI 2%
    PRS 89.2
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.17
    rCSI 6.78%
    PRS 89.59
  • rod bipolar cell CL0000751
    CSI 2.07
    rCSI 3.72%
    PRS 91.79
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.01
    rCSI 2.4%
    PRS 87.4
  • amacrine cell CL0000561
    CSI 1.99
    rCSI 5.77%
    PRS 89.7
  • retinal pigment epithelial cell CL0002586
    CSI 1.89
    rCSI 3.75%
    PRS 92.97
  • retinal cone cell CL0000573
    CSI 1.78
    rCSI 2.86%
    PRS 89.74
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.76
    rCSI 5.52%
    PRS 88.28
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.74
    rCSI 2.24%
    PRS 88.25
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.62
    rCSI 9.56%
    PRS 87.8
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.43
    rCSI 2.31%
    PRS 88.27
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.28
    rCSI 2.15%
    PRS 87.48
  • retinal ganglion cell CL0000740
    CSI 1.07
    rCSI 2.37%
    PRS 88.4
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.87
    rCSI 3.28%
    PRS 87.51
  • direct pathway medium spiny neuron CL4023026
    CSI 0.31
    rCSI 7.36%
    PRS 85.17
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.29
    rCSI 6.96%
    PRS 84.96

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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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • 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 [PDE6B](/details-gene/5158) encodes the beta-subunit of cGMP phosphodiesterase 6, an enzyme critical for the phototransduction cascade in the retina. As a key component of the PDE6 holoenzyme, it is responsible for hydrolyzing cyclic GMP (cGMP) in response to light, leading to the closure of cGMP-gated cation channels and hyperpolarization of photoreceptor cells. **Overall**, expression data reveals that [PDE6B](/details-gene/5158) is overwhelmingly significant in [retinal rod cell](/details-cell/CL0000604)s, underscoring its indispensable role in scotopic (low-light) vision. Mutations in this gene are clinically associated with hereditary retinal diseases, including autosomal recessive retinitis pigmentosa ([163500](https://omim.org/entry/163500)) and autosomal dominant congenital stationary night blindness ([180072](https://omim.org/entry/180072)), highlighting its non-redundant function in maintaining photoreceptor health and function. ## Cellular Roles and Expression Landscape The expression profile of [PDE6B](/details-gene/5158) demonstrates profound specificity for retinal photoreceptors. Its highest significance is observed in [retinal rod cell](/details-cell/CL0000604)s (CSI: 19.29), which is substantially greater than in any other cell type, firmly establishing it as a defining functional marker for these cells. This is consistent with its canonical role in rod-mediated vision. The gene also shows notable, albeit lower, significance in other cells of the retina, including [S cone cell](/details-cell/CL0003050), [retinal bipolar neuron](/details-cell/CL0000748), and [amacrine cell](/details-cell/CL0000561), suggesting a broader involvement within the retinal neurocircuitry than exclusively in rods. Interestingly, [PDE6B](/details-gene/5158) also exhibits significant expression in several neuronal subtypes outside the retina, particularly [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) and various glutamatergic neurons. This observation is supported by early research that provided evidence for its expression in the brain ([Link](https://doi.org/10.1016/0888-7543(92)90144-h)), suggesting a potential extra-retinal role for cGMP signaling modulation in cortical circuits. The expression in [hematopoietic stem cell](/details-cell/CL0000037)s and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)s indicates a possible, though less characterized, function in hematopoiesis. The gene's general absence from major immune, stromal, and non-ciliated epithelial lineages further highlights its specialized role in sensory and neuronal signal transduction. ## Pathways and Molecular Function [PDE6B](/details-gene/5158) is fundamentally involved in sensory perception, primarily through its role in the visual phototransduction cascade. Its molecular function is centered on its 3',5'-cyclic-GMP phosphodiesterase activity ([GO:0047555](https://www.ebi.ac.uk/QuickGO/term/GO:0047555)), which is a critical step in converting a light stimulus into an electrochemical signal. This activity is integral to the Reactome pathway 'The phototransduction cascade' ([R-HSA-2514856](https://reactome.org/content/detail/R-HSA-2514856)) and 'Visual phototransduction' ([R-HSA-2187338](https://reactome.org/content/detail/R-HSA-2187338)). The gene product localizes to the [photoreceptor outer segment membrane](/details-cell/GO:0042622) and [photoreceptor disc membrane](/details-cell/GO:0097381), the precise subcellular locations where these signaling events occur. Beyond vision, functional annotations suggest a broader role in signal transduction ([R-HSA-162582](https://reactome.org/content/detail/R-HSA-162582)), including involvement in the [Ca2+ pathway](/details-cell/R-HSA-4086398) and [beta-catenin independent Wnt signaling](/details-cell/R-HSA-3858494). This indicates that the cGMP-modulating activity of [PDE6B](/details-gene/5158) may be integrated with other major cellular signaling networks, which could be relevant to its function in both retinal and extra-retinal contexts. ## Research Directions The highly specific expression and critical function of [PDE6B](/details-gene/5158) in retinal photoreceptors are well-established, but its significance in other neuronal populations remains an area for further investigation. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis on Extra-Retinal Function:** The significant expression of [PDE6B](/details-gene/5158) in cortical neurons, such as [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s, suggests it plays a functional role in regulating neuronal excitability. We hypothesize that [PDE6B](/details-gene/5158) modulates local cGMP concentrations in these interneurons to fine-tune synaptic transmission and plasticity, contributing to cortical circuit function. 2. **Hypothesis on Disease Pathogenicity:** Given that heterozygous mutations can cause autosomal dominant stationary night blindness ([Link](https://doi.org/10.1038/ng0594-64)), we hypothesize that certain missense mutations in [PDE6B](/details-gene/5158) exert a dominant-negative effect. This could occur by producing a catalytically impaired but structurally stable protein that incorporates into the PDE6 holoenzyme, disrupting the function of the complex even when a wild-type allele is present. 3. **Hypothesis on Cone Photoreceptor Function:** The notable expression of [PDE6B](/details-gene/5158) in [S cone cell](/details-cell/CL0003050)s suggests it may contribute to phototransduction in cones, not just rods. We hypothesize that [PDE6B](/details-gene/5158) can substitute for or work alongside the cone-specific PDE6C subunit under certain conditions, potentially influencing the kinetics or light adaptation of cone photoreceptor responses. **Experimental Approach to Test Hypothesis 1:** To investigate the role of [PDE6B](/details-gene/5158) in cortical interneurons, a conditional knockout mouse model could be generated to specifically delete [PDE6B](/details-gene/5158) in parvalbumin-expressing neurons. Electrophysiological recordings (e.g., whole-cell patch-clamp) could then be performed on brain slices from these mice to measure changes in membrane properties, firing rates, and synaptic currents in [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s. Furthermore, applying cGMP analogs or phosphodiesterase inhibitors during recordings would help elucidate the specific contribution of the cGMP pathway to the observed phenotypes. **Therapeutic Potential:** As loss-of-function mutations in [PDE6B](/details-gene/5158) lead to retinal degeneration ([Link](https://doi.org/10.1038/ng0693-130); [Link](https://doi.org/10.1006/geno.1995.0001)), therapeutic strategies should focus on **gene replacement or augmentation** rather than inhibition. The high specificity of its expression in photoreceptors makes it an excellent candidate for AAV-mediated gene therapy. Delivering a functional copy of the [PDE6B](/details-gene/5158) cDNA via subretinal injection could restore PDE6 function, prevent photoreceptor cell death, and preserve vision in patients with [PDE6B](/details-gene/5158)-associated retinitis pigmentosa. This approach has shown promise for other monogenic retinal dystrophies and represents the most direct path to a potential cure.

Genular Protein ID: 648791670

Symbol: PDE6B_HUMAN

Name: N/A

UniProtKB Accession Codes:

P35913 B7Z9T9 E7ETT3 Q53XN5 Q9BWH5 Q9UD49

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChEBI 10 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 1 EMBL 14 Ensembl 3 ExpressionAtlas 1 GO 12 Gene3D 2 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 3 RefSeq 5 Rhea 2 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 1720239

Title: Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p16.3.

PubMed ID: 1720239

DOI: 10.1093/nar/19.22.6263

PubMed ID: 1338685

Title: Structural studies of cDNA and the gene for the beta-subunit of cGMP phosphodiesterase from human retina.

PubMed ID: 1338685

PubMed ID: 1322354

Title: The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain.

PubMed ID: 1322354

DOI: 10.1016/0888-7543(92)90144-h

PubMed ID: 8394243

Title: The human rod photoreceptor cGMP phosphodiesterase beta-subunit. Structural studies of its cDNA and gene.

PubMed ID: 8394243

DOI: 10.1016/0014-5793(93)81003-i

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 8075643

Title: Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness.

PubMed ID: 8075643

DOI: 10.1038/ng0594-64

PubMed ID: 7951329

Title:

PubMed ID: 7951329

DOI: 10.1038/ng0894-551a

PubMed ID: 8768262

Title: Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase.

PubMed ID: 8768262

PubMed ID: 8394174

Title: Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa.

PubMed ID: 8394174

DOI: 10.1038/ng0693-130

PubMed ID: 20940301

Title: Rod phosphodiesterase-6 PDE6A and PDE6B subunits are enzymatically equivalent.

PubMed ID: 20940301

DOI: 10.1074/jbc.m110.170068

PubMed ID: 8595886

Title: Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa.

PubMed ID: 8595886

DOI: 10.1006/geno.1995.0001

PubMed ID: 8698075

Title: Screening of the PDE6B gene in patients with autosomal dominant retinitis pigmentosa.

PubMed ID: 8698075

DOI: 10.1006/exer.1996.0019

PubMed ID: 8557257

Title: A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family.

PubMed ID: 8557257

DOI: 10.1007/bf00218829

PubMed ID: 8956055

Title: Identification of a novel R552Q mutation in exon 13 of the beta-subunit of rod phosphodiesterase gene in a Spanish family with autosomal recessive retinitis pigmentosa.

PubMed ID: 8956055

DOI: 10.1002/humu.1380080403

PubMed ID: 9543643

Title: A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase beta-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa.

PubMed ID: 9543643

DOI: 10.1076/ceyr.17.3.332.5214

PubMed ID: 22334370

Title: Next-generation genetic testing for retinitis pigmentosa.

PubMed ID: 22334370

DOI: 10.1002/humu.22045

Sequence Information:

  • Length: 854
  • Mass: 98336
  • Checksum: BB11A519BE88C9DF
  • Sequence:
    • MSLSEEQARS FLDQNPDFAR QYFGKKLSPE NVAAACEDGC PPDCDSLRDL CQVEESTALL 
ELVQDMQESI NMERVVFKVL RRLCTLLQAD RCSLFMYRQR NGVAELATRL FSVQPDSVLE 
DCLVPPDSEI VFPLDIGVVG HVAQTKKMVN VEDVAECPHF SSFADELTDY KTKNMLATPI 
MNGKDVVAVI MAVNKLNGPF FTSEDEDVFL KYLNFATLYL KIYHLSYLHN CETRRGQVLL 
WSANKVFEEL TDIERQFHKA FYTVRAYLNC ERYSVGLLDM TKEKEFFDVW SVLMGESQPY 
SGPRTPDGRE IVFYKVIDYV LHGKEEIKVI PTPSADHWAL ASGLPSYVAE SGFICNIMNA 
SADEMFKFQE GALDDSGWLI KNVLSMPIVN KKEEIVGVAT FYNRKDGKPF DEQDEVLMES 
LTQFLGWSVM NTDTYDKMNK LENRKDIAQD MVLYHVKCDR DEIQLILPTR ARLGKEPADC 
DEDELGEILK EELPGPTTFD IYEFHFSDLE CTELDLVKCG IQMYYELGVV RKFQIPQEVL 
VRFLFSISKG YRRITYHNWR HGFNVAQTMF TLLMTGKLKS YYTDLEAFAM VTAGLCHDID 
HRGTNNLYQM KSQNPLAKLH GSSILERHHL EFGKFLLSEE TLNIYQNLNR RQHEHVIHLM 
DIAIIATDLA LYFKKRAMFQ KIVDESKNYQ DKKSWVEYLS LETTRKEIVM AMMMTACDLS 
AITKPWEVQS KVALLVAAEF WEQGDLERTV LDQQPIPMMD RNKAAELPKL QVGFIDFVCT 
FVYKEFSRFH EEILPMFDRL QNNRKEWKAL ADEYEAKVKA LEEKEEEERV AAKKVGTEIC 
NGGPAPKSST CCIL

Genular Protein ID: 3982041041

Symbol: B4DHV7_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DHV7

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 10 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 2 InterPro 7 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSR 3 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 RuleBase 1 SAM 1 SMART 2 SMR 1 SUPFAM 2

Sequence Information:

  • Length: 575
  • Mass: 66409
  • Checksum: 61A48F882C2613A7
  • Sequence:
    • MTKEKEFFDV WSVLMGESQP YSGPRTPDGR EIVFYKVIDY ILHGKEEIKV IPTPSADHWA 
LASGLPSYVA ESGFICNIMN ASADEMFKFQ EGALDDSGWL IKNVLSMPIV NKKEEIVGVA 
TFYNRKDGKP FDEQDEVLME SLTQFLGWSV MNTDTYDKMN KLENRKDIAQ DMVLYHVKCD 
GDEIQLILPT RARLGKEPAD CDEDELGEIL KEELPGPTTF DIYEFHFSDL ECTELDLVKC 
GIQMYYELGV VRKFQIPQEV LVRFLFSISK GYRRITYHNW RHGFNVAQTM FTLLMTGKLK 
SYYTDLEAFA MVTAGLCHDI DHRGTNNLYQ MKSQNPLAKL HGSSILERHH LEFGKFLLSE 
ETLNIYQNLN RRQHEHVIHL MDIAIIATDL ALYFKKRAMF QKIVDESKNY QDKKSWVEYL 
SLETTRKEIV MAMMMTACDL SAITKPWEVQ SKVALLVAAE FWEQGDLERT VLDQQPIPMM 
DRNKAAELPK LQVGFIDFVC TFVYKEFSRF HEEILPMFDR LQNNRKEWKA LADEYEAKVK 
ALEEKEEEER VAAKKVGTEI CNGGPAPKSS TCCIL