Details for: CL0000648

Cell ID: CL0000648

Cell Name: kidney granular cell

Description: A smooth muscle cell that synthesizes, stores, and secretes the enzyme renin. This cell type are located in the wall of the afferent arteriole at the entrance to the glomerulus. While having a different origin than other kidney smooth muscle cells, this cell type expresses smooth muscle actin upon maturation.

Synonyms: JG cell, juxtaglomerular cell, renin secreting cell

Selected Context(s): Overall

Gene Significance Landscape

Display Options
Score:
Display
Genes

Contexts:

Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for kidney granular cell within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for kidney granular cell. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for kidney granular cell. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for kidney granular cell. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

Maximum number of selected genes.
Select a context for the baseline cell.
Select a context for the target cell.
Target Cell for CSI:  kidney granular cell (CL0000648)

 Legend
Nodes (Genes):
 Query Gene
Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
 Very High
 High
 Medium
 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

Loading network (please wait)...

## Summary The [kidney granular cell](/details-cell/CL0000648), also known as a juxtaglomerular (JG) cell, is a specialized smooth muscle cell located in the afferent arteriole of the kidney glomerulus, primarily known for synthesizing and secreting renin. The provided gene significance profile highlights this cell's unique identity, which is strongly defined by an unusual mitochondrial signature and a robust machinery for ion transport and extracellular matrix modulation. **Overall**, the top markers ([RNR1](/details-gene/4549), [RNR2](/details-gene/4550)) suggest a high capacity for mitochondrial protein synthesis, while other key genes like [ATP1B1](/details-gene/481) and [MGP](/details-gene/4256) underscore its critical role in ion homeostasis and maintaining vascular integrity, consistent with its function in blood pressure regulation. ## Key Characteristics and Function Analysis of the top marker genes reveals several interconnected functional themes that define the [kidney granular cell](/details-cell/CL0000648). * **Ion Transport and Electrophysiology:** A prominent functional signature of this cell is its extensive set of genes involved in ion transport. This includes [ATP1B1](/details-gene/481) (Na,K-ATPase beta subunit), [SLC8A1](/details-gene/6546) (a Na+/Ca2+ exchanger), [KCNJ1](/details-gene/3758) (an inwardly rectifying potassium channel), [FXYD2](/details-gene/486) (the gamma subunit of Na,K-ATPase), and [SLC12A1](/details-gene/6557) (a Na-K-2Cl cotransporter). This complex array of transporters suggests the cell is meticulously involved in maintaining precise electrochemical gradients, a function essential for sensing changes in blood pressure and tubular fluid composition. * **Extracellular Matrix (ECM) Interaction and Secretion:** The cell appears to be highly engaged in managing its local microenvironment. Significant markers include [MGP](/details-gene/4256), an inhibitor of tissue calcification, [TIMP3](/details-gene/7078), a metalloproteinase inhibitor, and [A2M](/details-gene/2), a broad-spectrum protease inhibitor. Furthermore, genes like [IGFBP7](/details-gene/3490), [IGFBP5](/details-gene/3488), and [SPARCL1](/details-gene/8404) are associated with growth factor binding and ECM organization. This suggests that [kidney granular cells](/details-cell/CL0000648) actively shape the structure and function of the arteriolar wall. * **Specialized Mitochondrial Activity:** The two most significant markers by `csi_z` score are the mitochondrial ribosomal RNAs [RNR1](/details-gene/4549) and [RNR2](/details-gene/4550). This points towards a high rate of mitochondrial translation. Paradoxically, numerous genes encoding core components of the mitochondrial electron transport chain (e.g., [COX1](/details-gene/4512), [COX2](/details-gene/4513), [ND4](/details-gene/4538), [ATP6](/details-gene/4508)) are among the strongest anti-markers for this cell type. This striking dichotomy suggests a highly specialized mitochondrial role that may prioritize functions other than bulk ATP production via oxidative phosphorylation. * **Metabolism and Signaling:** The significance of [ALDOB](/details-gene/229) points to activity in fructose metabolism. Intracellular signaling is highlighted by [PRKG1](/details-gene/5592), a cGMP-dependent protein kinase involved in smooth muscle relaxation, consistent with the cell's location and function in regulating vascular tone. The profile of anti-markers further refines the cell's identity. The strong negative significance for core housekeeping genes involved in ubiquitination ([UBB](/details-gene/7314), [UBC](/details-gene/7316)), iron storage ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)), and RNA processing ([HNRNPA2B1](/details-gene/3181), [DDX5](/details-gene/1655)), in addition to the previously mentioned mitochondrial respiratory genes, indicates a highly specialized and distinct cellular program compared to the average cell. ## Clinical Significance and Contextual Roles The gene signature of the [kidney granular cell](/details-cell/CL0000648) has direct and significant clinical implications, particularly in hereditary kidney diseases and hypertension. * **Channelopathies and Electrolyte Disorders:** Several of the top marker genes are directly implicated in human genetic disorders affecting kidney function. Mutations in [SLC12A1](/details-gene/6557) ([Link](https://doi.org/10.1038/ng0696-183)) and [KCNJ1](/details-gene/3758) are causative for Bartter's syndrome, a group of life-threatening salt-wasting nephropathies. Similarly, mutations in [FXYD2](/details-gene/486) are known to cause dominant isolated renal magnesium loss ([Link](https://doi.org/10.1038/81543)). The high specificity of these genes to [kidney granular cells](/details-cell/CL0000648) and related renal cell types underscores their central role in the pathophysiology of these conditions. * **Vascular Health and Calcification:** The high significance of [MGP](/details-gene/4256), a potent inhibitor of vascular calcification, suggests that these cells play a protective role in maintaining the integrity and flexibility of the afferent arteriole. Dysregulation of [MGP](/details-gene/4256) could contribute to renal vascular stiffness and impaired blood flow regulation, factors associated with chronic kidney disease and hypertension. * **Tissue Remodeling and Fibrosis:** The expression of [TIMP3](/details-gene/7078), a key inhibitor of matrix metalloproteinases, points to a role in controlling local tissue remodeling. In disease states, an imbalance in TIMP/MMP activity can lead to fibrosis or abnormal vascular structure, suggesting that dysfunction in [kidney granular cells](/details-cell/CL0000648) could contribute to the progression of kidney disease. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The unique mitochondrial profile, characterized by high expression of mitochondrial ribosomal RNAs ([RNR1](/details-gene/4549), [RNR2](/details-gene/4550]) and low expression of oxidative phosphorylation (OXPHOS) subunits (e.g., [COX1](/details-gene/4512), [ND4](/details-gene/4538)), suggests that [kidney granular cells](/details-cell/CL0000648) have uncoupled mitochondrial translation from energy production. This specialized state may be required to synthesize specific mitochondrial-encoded factors essential for their sensory or secretory functions, potentially at the cost of metabolic efficiency. * **Surprising Findings:** The stark opposition between the significance of mitochondrial translation machinery and respiratory chain components is highly unusual for a metabolically active cell. Additionally, the canonical marker for this cell, Renin (`REN`), is absent from the top markers list, which may indicate that its expression, while functionally critical, is less specific or abundant compared to the identified structural and metabolic genes in this dataset. * **Testable Questions:** What is the complete mitochondrial proteome of [kidney granular cells](/details-cell/CL0000648), and how does it differ from that of neighboring endothelial or non-granular smooth muscle cells? Does specific inhibition of mitochondrial translation, for example with chloramphenicol, disproportionately affect renin secretion compared to cellular ATP levels? 2. **Hypothesis:** The co-expression of a robust suite of ion transporters ([KCNJ1](/details-gene/3758), [SLC12A1](/details-gene/6557)) and potent extracellular matrix modulators ([MGP](/details-gene/4256), [TIMP3](/details-gene/7078)) suggests that [kidney granular cells](/details-cell/CL0000648) integrate electrochemical signals with physical control over their microenvironment. This dual function may allow them to act as mechanochemical sensors, simultaneously regulating arteriolar tone via ion fluxes and modulating the vessel's long-term structural properties through ECM remodeling. * **Surprising Findings:** The finding that ECM-related genes like [MGP](/details-gene/4256) and [SPARCL1](/details-gene/8404) have a specificity comparable to well-established ion channels suggests that maintaining the structural integrity and signaling capacity of the extracellular space is a primary, not secondary, function of these cells. * **Testable Questions:** How does stimulation of specific ion channels, such as the Na-K-2Cl cotransporter encoded by [SLC12A1](/details-gene/6557), alter the expression and secretion of ECM proteins like [MGP](/details-gene/4256) in primary [kidney granular cells](/details-cell/CL0000648)? Does knockout of [MGP](/details-gene/4256) in these cells lead to inappropriate calcification of the juxtaglomerular apparatus and a blunted renin response to hypotension?