Details for: CL1000849

Cell ID: CL1000849

Cell Name: kidney distal convoluted tubule epithelial cell

Description: Any epithelial cell of distal tubule that is part of some distal convoluted tubule.

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

Image representation

Depiction of kidney distal convoluted tubule epithelial cell
Courtesy of SwissBioPics

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for kidney distal convoluted tubule epithelial 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 distal convoluted tubule epithelial 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 distal convoluted tubule epithelial 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 distal convoluted tubule epithelial 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 distal convoluted tubule epithelial cell (CL1000849)

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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 [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849) is a highly specialized epithelial cell type responsible for the regulated reabsorption of ions and solutes in the final segment of the nephron. The **Overall** gene significance profile reveals that this cell's identity is overwhelmingly defined by a unique and pronounced expression of nuclear-encoded mitochondrial genes. The high cell-type specificity for numerous subunits of the electron transport chain, such as `[COX5B](/details-gene/1329)` and `[COX7C](/details-gene/1350)`, suggests that its primary characteristic is an immense and constitutively active aerobic respiration capacity, likely to fuel the intensive energy demands of active ion transport. ## Key Characteristics and Function Analysis of top marker genes, ranked by expression specificity (`csi_z`), highlights several core functional clusters that define the [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849). * **Mitochondrial Bioenergetics:** The most striking feature of this cell is its profound specialization in energy production. A large number of its top markers are components of the mitochondrial respiratory chain. These include multiple subunits of Cytochrome c oxidase (Complex IV), such as `[COX5B](/details-gene/1329)`, `[COX7C](/details-gene/1350)`, `[COX6C](/details-gene/1345)`, `[COX7A2](/details-gene/1347)`, and `[COX4I1](/details-gene/1327)`; a subunit of Complex I, `[NDUFA4](/details-gene/4697)`; subunits of ATP synthase (Complex V), including `[ATP5F1B](/details-gene/506)`, `[ATP5MG](/details-gene/10632)`, and `[ATP5ME](/details-gene/521)`; and a component of Complex III, `[UQCRB](/details-gene/7381)`. The high specificity of this entire gene set indicates that an exceptionally high metabolic rate is not just a feature but a defining characteristic of this cell's lineage. * **Ion Transport and Signaling:** The high energy production is directly linked to the cell's transport functions. The specific expression of the voltage-gated sodium channel alpha subunit, `[SCN2A](/details-gene/6326)`, points towards its role in sodium reabsorption. Furthermore, the presence of `[S100A6](/details-gene/6277)`, a calcium-binding protein, is consistent with the distal convoluted tubule's critical role in calcium homeostasis. * **Cellular Maintenance and Antigen Presentation:** Genes involved in general protein synthesis and trafficking, like the poly(A)-binding protein `[PABPC1](/details-gene/26986)` and signal recognition particle subunit `[SRP14](/details-gene/6727)`, are also specific markers, reflecting the constant need to maintain the cell's complex protein machinery. The significant expression of Beta-2-microglobulin (`[B2M](/details-gene/567)`), a component of MHC class I molecules, suggests these epithelial cells may participate in antigen presentation, providing a potential interface with the renal immune system. * **Anti-Markers:** The profile of genes with low or negative significance is also informative. Intriguingly, several mitochondrially-encoded genes, including `[COX1](/details-gene/4512)`, `[COX2](/details-gene/4513)`, `[COX3](/details-gene/4514)`, and `[ND3](/details-gene/4537)`, are anti-markers. This contrasts sharply with the high specificity of their nuclear-encoded counterparts and suggests a tightly regulated, specific stoichiometry between components of the respiratory complexes that is unique to this cell type. ## Clinical Significance and Contextual Roles While this analysis is based on an **Overall** context, the specific gene signature of the [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849) has several potential clinical implications. * **Channelopathies and Renal Function:** The high specificity of `[SCN2A](/details-gene/6326)`, a gene primarily known for its association with severe neurodevelopmental disorders like epileptic encephalopathy, is a striking finding. This suggests that `[SCN2A](/details-gene/6326)` mutations could potentially manifest with subclinical or uncharacterized renal phenotypes, or that the gene performs a distinct, non-canonical function in the kidney. * **Metabolic and Toxin-Related Injury:** The specific expression of `[GSTP1](/details-gene/2950)`, a key enzyme in detoxification pathways, underscores the cell's role in handling metabolic byproducts and xenobiotics. Dysregulation of `[GSTP1](/details-gene/2950)` could modulate the cell's susceptibility to drug-induced nephrotoxicity or oxidative stress-related kidney damage. * **Novel Signaling Pathways:** The presence of `[NRG3](/details-gene/10718)`, a neural-enriched ligand for the ErbB4 receptor, as a highly specific marker is unexpected. This may indicate a previously unappreciated signaling pathway in the distal tubule, potentially involved in paracrine communication, cellular homeostasis, or regenerative responses following injury. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849) achieves its extreme bioenergetic capacity through a unique regulatory program that prioritizes the expression and import of specific nuclear-encoded mitochondrial protein subunits over the expression of mitochondrial-encoded subunits. This creates a distinct, cell-type-specific stoichiometry of respiratory chain complexes optimized for sustained, high-level ATP production. * **Surprising Findings:** The most surprising finding is the diametrically opposed significance scores for nuclear-encoded (`[COX5B](/details-gene/1329)`, `[COX7C](/details-gene/1350)`) versus mitochondrial-encoded (`[COX1](/details-gene/4512)`, `[COX2](/details-gene/4513)`) subunits of the same enzymatic complex. This challenges the assumption of simple co-regulation and suggests a sophisticated, lineage-specific control mechanism. * **Testable Questions:** How does the protein ratio of nuclear- to mitochondrial-encoded subunits of Complex IV differ between [kidney distal convoluted tubule epithelial cells](/details-cell/CL1000849) and other kidney epithelial cells, and is this ratio altered in models of mitochondrial kidney disease? 2. **Hypothesis:** Proteins traditionally associated with the nervous system, particularly the ion channel `[SCN2A](/details-gene/6326)` and the signaling ligand `[NRG3](/details-gene/10718)`, have been repurposed in the [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849) to form a "neuro-renal" sensory and communication network that regulates electrolyte balance. `[SCN2A](/details-gene/6326)` may act as a sensor for luminal sodium concentration, while `[NRG3](/details-gene/10718)` could mediate paracrine signals that coordinate transport activity along the tubule. * **Surprising Findings:** The high specificity (`csi_z`) of multiple, well-characterized neuronal genes within a renal epithelial cell is unexpected. It suggests that our understanding of these genes' functions may be incomplete and that they could be key players in organ systems beyond the brain. * **Testable Questions:** Does conditional knockout of `[SCN2A](/details-gene/6326)` or its receptor ErbB4 in the distal convoluted tubule of a mouse model lead to defects in sodium and calcium homeostasis, particularly under conditions of dietary electrolyte stress?