Details for: GRK7

Gene ID: 131890

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: GRK7

Ensembl ID: ENSG00000114124

Description: G protein-coupled receptor kinase 7

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal cone cell CL0000573
    CSI 2.68
    rCSI 4.31%
    PRS 99.08

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 [GRK7](/details-gene/131890) (G protein-coupled receptor kinase 7) is a protein-coding gene located on chromosome 3 that encodes a rhodopsin kinase. This enzyme plays a highly specialized and critical role in the visual system. Functional annotations and expression data strongly indicate that [GRK7](/details-gene/131890) is essential for the process of visual phototransduction, particularly in the deactivation of light-activated cone opsins. Its expression is remarkably restricted, with data showing its highest significance almost exclusively in '[retinal cone cell](/details-cell/CL0000573)'. This specificity is consistent with its function as a primary kinase responsible for terminating the light response in cones, thereby allowing for rapid recovery and adaptation to changing light conditions [Link](https://pubmed.ncbi.nlm.nih.gov/11754336/). ## Cellular Roles and Expression Landscape The expression profile of [GRK7](/details-gene/131890) is characterized by its exceptional specificity for a single cell type within the human retina. **Overall**, the gene demonstrates its highest significance as a defining marker for the '[retinal cone cell](/details-cell/CL0000573)' (CSI: 2.68). This highly restricted expression pattern underscores its specialized function in color and high-acuity vision. This specificity suggests that [GRK7](/details-gene/131890) is not a general signaling molecule but rather a purpose-built component of the cone phototransduction machinery. Research has confirmed this specificity, identifying GRK7 as the likely cone opsin kinase in primates, in contrast to GRK1, which serves a similar function in rod cells [Link](https://doi.org/10.1523/jneurosci.21-23-09175.2001). The lack of significant expression in other cell types implies a finely tuned regulatory system that confines its activity to the precise cellular environment where its substrate, cone opsins, is located. ## Pathways and Molecular Function The molecular function of [GRK7](/details-gene/131890) is centered on its role within the visual cycle. As a kinase, its primary molecular functions include '[rhodopsin kinase activity](/details-go/GO:0050254)' and '[ATP binding](/details-go/GO:0005524)', which are prerequisites for its enzymatic phosphorylation of target proteins. This activity is situated within the '[photoreceptor disc membrane](/details-go/GO:0097381)', the precise subcellular location where visual pigments are housed. These molecular functions are integral to the biological process of '[visual perception](/details-go/GO:0007601)' and specifically the '[regulation of opsin-mediated signaling pathway](/details-go/GO:0022400)'. According to Reactome, [GRK7](/details-gene/131890) is a key player in '[The phototransduction cascade](/details-pathway/R-HSA-2514856)', contributing specifically to the '[inactivation, recovery and regulation of the phototransduction cascade](/details-pathway/R-HSA-2514859)'. Upon light activation, cone opsins must be rapidly phosphorylated to allow for the binding of arrestin, which terminates the signal. [GRK7](/details-gene/131890) performs this critical phosphorylation step. Furthermore, its own activity is subject to regulation; studies have shown that its enzymatic function is attenuated by phosphorylation via cAMP-dependent protein kinase (PKA) [Link](https://doi.org/10.1074/jbc.m505117200), a process that is itself regulated by light levels in cone photoreceptors [Link](https://doi.org/10.1111/j.1471-4159.2008.05691.x). ## Research Directions The provided data highlights the extreme cell-type specificity of [GRK7](/details-gene/131890) but does not include comparative analyses across different biological contexts, such as health versus disease. Future research should focus on its potential role in retinal pathologies. **Testable Hypotheses:** 1. Given its critical role in cone function, loss-of-function mutations in `[GRK7](/details-gene/131890)` are likely a cause of currently uncharacterised inherited retinal diseases, such as cone dystrophies or forms of day blindness (hemeralopia), where patients experience impaired vision in bright light. 2. The known regulation of `[GRK7](/details-gene/131890)` activity by PKA-mediated phosphorylation [Link](https://doi.org/10.1111/j.1471-4159.2008.05691.x) is a key mechanism for light adaptation in cones. Dysregulation of this pathway, either through mutations in `[GRK7](/details-gene/131890)` phosphorylation sites or in upstream regulators, may lead to an inability to adapt to changing light conditions, resulting in prolonged photostress recovery. **Proposed Experiment:** To test the hypothesis that `[GRK7](/details-gene/131890)` mutations cause cone dystrophies, a targeted sequencing panel for this gene could be applied to a patient cohort with inherited cone-related visual impairment of unknown genetic origin. Variants identified in patients would be functionally characterized by cloning them into expression vectors and testing the kinase activity of the mutant protein against a cone opsin substrate in vitro. For in vivo validation, a CRISPR-Cas9-based mouse model harboring a patient-identified mutation could be generated. Cone function in these mice would be assessed using cone-specific electroretinography (ERG) under photopic (light-adapted) conditions to measure deficits in the cone-mediated light response and recovery. **Therapeutic Potential:** [GRK7](/details-gene/131890) is not a viable target for therapeutic inhibition, as this would impair vision. Instead, it represents an ideal candidate for gene augmentation therapy for retinal diseases caused by its deficiency. The highly restricted expression of [GRK7](/details-gene/131890) in '[retinal cone cell](/details-cell/CL0000573)' is advantageous for this approach. A therapeutic strategy would likely involve subretinal injection of an adeno-associated virus (AAV) vector carrying a functional copy of the `[GRK7](/details-gene/131890)` cDNA under the control of a cone-specific promoter. This would aim to restore kinase activity only in the affected cells, minimizing the risk of off-target effects.

Genular Protein ID: 4198098454

Symbol: GRK7_HUMAN

Name: Rhodopsin kinase GRK7

UniProtKB Accession Codes:

Q8WTQ7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 2 EMBL 3 Ensembl 2 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 6 SABIO-RK 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11754336

Title: Characterization of human GRK7 as a potential cone opsin kinase.

PubMed ID: 11754336

PubMed ID: 11717351

Title: Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction.

PubMed ID: 11717351

DOI: 10.1523/jneurosci.21-23-09175.2001

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 15946941

Title: Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities.

PubMed ID: 15946941

DOI: 10.1074/jbc.m505117200

PubMed ID: 18803695

Title: Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light.

PubMed ID: 18803695

DOI: 10.1111/j.1471-4159.2008.05691.x

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 553
  • Mass: 62212
  • Checksum: C502E301CF8EB688
  • Sequence:
    • MVDMGALDNL IANTAYLQAR KPSDCDSKEL QRRRRSLALP GLQGCAELRQ KLSLNFHSLC 
EQQPIGRRLF RDFLATVPTF RKAATFLEDV QNWELAEEGP TKDSALQGLV ATCASAPAPG 
NPQPFLSQAV ATKCQAATTE EERVAAVTLA KAEAMAFLQE QPFKDFVTSA FYDKFLQWKL 
FEMQPVSDKY FTEFRVLGKG GFGEVCAVQV KNTGKMYACK KLDKKRLKKK GGEKMALLEK 
EILEKVSSPF IVSLAYAFES KTHLCLVMSL MNGGDLKFHI YNVGTRGLDM SRVIFYSAQI 
ACGMLHLHEL GIVYRDMKPE NVLLDDLGNC RLSDLGLAVE MKGGKPITQR AGTNGYMAPE 
ILMEKVSYSY PVDWFAMGCS IYEMVAGRTP FKDYKEKVSK EDLKQRTLQD EVKFQHDNFT 
EEAKDICRLF LAKKPEQRLG SREKSDDPRK HHFFKTINFP RLEAGLIEPP FVPDPSVVYA 
KDIAEIDDFS EVRGVEFDDK DKQFFKNFAT GAVPIAWQEE IIETGLFEEL NDPNRPTGCE 
EGNSSKSGVC LLL