Details for: CL0005011

Cell ID: CL0005011

Cell Name: renal alpha-intercalated cell

Description: A cuboidal epithelial cell of the kidney which secretes acid and reabsorbs base to regulate acid/base balance.

Synonyms: type A intercalated cell, type A-IC

Selected Context(s): Overall

Gene Significance Landscape

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Genes

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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 renal alpha-intercalated 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 renal alpha-intercalated 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 renal alpha-intercalated 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 renal alpha-intercalated 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:  renal alpha-intercalated cell (CL0005011)

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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.

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## Summary The [renal alpha-intercalated cell](/details-cell/CL0005011) is a specialized epithelial cell within the kidney's collecting duct, primarily defined by its crucial role in maintaining systemic acid-base homeostasis through active proton secretion. Gene significance analysis reveals that this cell's identity is overwhelmingly characterized by a profound and specific enrichment of genes encoding components of the mitochondrial electron transport chain. This signature suggests that the cell's function is powered by an exceptionally high rate of aerobic respiration, which generates the vast amounts of ATP required for the proton pumps that mediate urinary acidification. ## Key Characteristics and Function **Overall**, the gene expression profile of the [renal alpha-intercalated cell](/details-cell/CL0005011) points to a highly specialized metabolic engine optimized for energy-intensive ion transport. The most specific markers, identified by high z-score based Cell Significance Index (CSI), cluster into distinct functional groups that collectively define the cell's core purpose. * **Mitochondrial Respiration and Bioenergetics:** The most striking feature of this cell is the exceptional specificity of numerous genes encoding subunits of the mitochondrial respiratory chain. This includes [NDUFA4](/details-gene/4697) (CSI: 76.05) of Complex I, [UQCRB](/details-gene/7381) (CSI: 69.02) of Complex III, and a remarkable number of cytochrome c oxidase (Complex IV) subunits, such as [COX7C](/details-gene/1350) (CSI: 73.93), [COX7A2](/details-gene/1347) (CSI: 66.13), [COX5B](/details-gene/1329) (CSI: 44.23), and [COX6A1](/details-gene/1337) (CSI: 38.69). The high specificity of these components suggests that not just the quantity, but the specific composition of the respiratory machinery is a defining feature of this cell. This massive energy-generating capacity is directly linked to its transport function, exemplified by the significant expression of [ATP1B1](/details-gene/481) (CSI: 59.06), a subunit of the Na+/K+-ATPase pump essential for maintaining cellular ion gradients. * **Iron Metabolism and Oxidative Stress Management:** Consistent with the high density of iron-containing cytochromes, the ferritin light chain gene [FTL](/details-gene/2512) (CSI: 67.25) is a top marker. This indicates a specialized capacity for iron storage and handling, which is critical for assembling the respiratory complexes and mitigating iron-induced oxidative stress. The significant expression of [GSTP1](/details-gene/2950) (CSI: 31.81), a glutathione S-transferase, further supports the presence of robust mechanisms to detoxify reactive oxygen species generated as a byproduct of intense mitochondrial activity. * **Protein Synthesis and Turnover:** The cell also displays high specificity for genes involved in general protein synthesis and processing, such as the translation elongation factor [EEF1B2](/details-gene/1933) (CSI: 57.05) and the signal recognition particle subunit [SRP14](/details-gene/6727) (CSI: 64.76). The ubiquitin gene [UBB](/details-gene/7314) (CSI: 55.22) also shows high specificity, suggesting that a high rate of protein turnover is necessary to maintain the integrity of the cell's complex machinery. * **Anti-Markers:** The genes with the lowest significance provide context for what this cell is *not*. The negative CSI scores for nucleolin ([NCL](/details-gene/4691)), calmodulin ([CALM1](/details-gene/801)), and several heterogeneous nuclear ribonucleoproteins like [HNRNPU](/details-gene/3192) suggest that the cell's defining transcriptional and signaling programs are highly focused. The low ranking of the major histocompatibility gene [HLA E](/details-gene/3133) is consistent with a primary metabolic and transport role rather than one in adaptive immune surveillance. ## Clinical Significance and Contextual Roles The gene profile of the [renal alpha-intercalated cell](/details-cell/CL0005011) underscores its critical role in renal physiology and its potential involvement in pathology. Given its primary function in acid secretion, dysfunction of these cells is a direct cause of distal renal tubular acidosis (dRTA), a condition characterized by an inability to acidify urine. The profound dependence on a specific suite of mitochondrial proteins renders these cells potential targets in mitochondrial diseases or toxic nephropathies caused by drugs that impair the electron transport chain. The high specificity of genes like [NDUFA4](/details-gene/4697) and multiple `COX` subunits suggests that genetic defects in these specific isoforms could manifest with a primary renal phenotype. Furthermore, the cell's reliance on iron, highlighted by the high specificity of [FTL](/details-gene/2512), may make it particularly sensitive to disorders of iron metabolism. The co-expression of protective enzymes like [GSTP1](/details-gene/2950) suggests an intrinsic vulnerability to oxidative stress, which could be exacerbated in conditions like ischemia-reperfusion injury or diabetic nephropathy. ## Potential Mechanisms and Research Directions 1. **Hypothesis: The renal alpha-intercalated cell possesses a uniquely configured mitochondrial proteome that is stoichiometrically optimized to maximize ATP production for V-type ATPase-mediated proton pumping.** The data show that it is not merely an abundance of mitochondria, but the high specificity of numerous, distinct subunits across the electron transport chain ([NDUFA4](/details-gene/4697), [UQCRB](/details-gene/7381), [COX7C](/details-gene/1350)) that defines this cell. This suggests a specialized, highly efficient respiratory supercomplex assembly geared towards sustained, high-volume ATP synthesis. * **Surprising Findings:** The striking number of different Complex IV (cytochrome c oxidase) subunits ([COX7C](/details-gene/1350), [COX7A2](/details-gene/1347), [COX5B](/details-gene/1329), [COX6A1](/details-gene/1337)) among the top markers is notable. This may indicate the assembly of a specific COX isoform or supercomplex that is uniquely suited to the metabolic demands and intracellular environment of this cell type. * **Testable Questions:** Does knockdown of these specific `COX` subunits in a renal epithelial cell model disproportionately reduce proton secretion compared to their effect on overall cellular ATP levels, suggesting a tight functional coupling between this specific ETC configuration and the apical proton pump? 2. **Hypothesis: The high specificity of ferritin ([FTL](/details-gene/2512)) reflects an essential, localized iron-buffering system that is critical for both the biogenesis of the dense respiratory chain and the prevention of Fenton-reaction-mediated oxidative damage.** The intense rate of respiration would generate significant oxidative stress, while the high density of heme- and iron-sulfur-containing proteins creates a massive demand for iron. [FTL](/details-gene/2512) may therefore serve a dual role: acting as a local iron reservoir for mitochondrial protein synthesis and sequestering free iron to protect the cell from its toxic effects. * **Surprising Findings:** It is unexpected to find an iron storage protein, typically considered a housekeeping gene, as one of the most specific markers of a cell type. This suggests its function here is highly specialized and integral to the cell's primary physiological purpose, on par with the respiratory components themselves. * **Testable Questions:** How does acute iron chelation or overload affect the acidification capacity of [renal alpha-intercalated cells](/details-cell/CL0005011) in primary culture or in vivo? Furthermore, does modulating [FTL](/details-gene/2512) expression directly impact the stability and assembly of mitochondrial respiratory complexes in these cells?