Details for: TNKS2 DT

Gene ID: 100507633

Gene Type:  ncRNA (Non-coding RNA)  - A functional RNA molecule that is transcribed from DNA but not translated into a protein. Includes classes like miRNA and lncRNA.

Symbol: TNKS2 DT

Ensembl ID: ENSG00000228701

Description: TNKS2 divergent transcript

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Significant Cells

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

  • neural progenitor cell CL0011020
    CSI 10.19
    rCSI 44.85%
    PRS 8.36
  • basal cell of epidermis CL0002187
    CSI 2.63
    rCSI 4.66%
    PRS 9.75
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.96
    rCSI 2.38%
    PRS 11.91
  • melanocyte of skin CL1000458
    CSI 1.76
    rCSI 2.4%
    PRS 5.38
  • conventional dendritic cell CL0000990
    CSI 0.36
    rCSI 0.3%
    PRS 26.07
  • helper T cell CL0000912
    CSI -0.14
    rCSI -0.19%
    PRS 12.04
  • innate lymphoid cell CL0001065
    CSI -4.29
    rCSI -8.85%
    PRS 13.18
  • suprabasal keratinocyte CL4033013
    CSI -8.13
    rCSI -13.28%
    PRS 5.73

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)

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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 *TNKS2 DT* (*TNKS2 divergent transcript*) is a long non-coding RNA ([lncRNA](/details-gene/100507633)) located on human chromosome 10. Its genomic position and nomenclature suggest a potential regulatory relationship with the adjacent protein-coding gene *TNKS2*, which encodes a key enzyme in Wnt signaling and telomere maintenance. Expression data indicates that `[TNKS2 DT](/details-gene/100507633)` is a highly specific marker for progenitor and stem-like cell populations. **Overall**, it shows the most significant expression in `[neural progenitor cell](/details-cell/CL0011020)` and `[basal cell of epidermis](/details-cell/CL0002187)`, suggesting a role in maintaining an undifferentiated state. It is also notably expressed in specific immune subsets, including `[CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)`, indicating specialized functions within the immune system. ## Cellular Roles and Expression Landscape The expression pattern of `[TNKS2 DT](/details-gene/100507633)` points towards a specialized role in regulating cell fate and differentiation, particularly in regenerative tissues and the immune system. **Overall**, the gene's most significant expression is observed in progenitor populations. It is a top marker in `[neural progenitor cell](/details-cell/CL0011020)` (CSI: 10.19) and the regenerative `[basal cell of epidermis](/details-cell/CL0002187)` (CSI: 2.63). This pattern suggests a potential function in preserving stemness or regulating early lineage commitment. Its expression in `[melanocyte of skin](/details-cell/CL1000458)`, which are derived from the neural crest, further supports a role within neuroectodermal lineages. Within the immune system, `[TNKS2 DT](/details-gene/100507633)` exhibits a selective expression profile. It is significantly expressed in `[CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)` and `[conventional dendritic cell](/details-cell/CL0000990)`, suggesting a function in adaptive immunity, possibly related to memory cell formation or antigen presentation. This specificity is highlighted by its markedly low expression in more differentiated or distinct cell types. A striking contrast is seen in the epidermis, where it is high in basal progenitors but has a strongly negative significance in their differentiated progeny, the `[suprabasal keratinocyte](/details-cell/CL4033013)` (CSI: -8.13). This sharp downregulation is consistent with a role in suppressing differentiation. Furthermore, its low expression in other immune populations, such as `[innate lymphoid cell](/details-cell/CL0001065)` and `[helper T cell](/details-cell/CL0000912)`, underscores its specialized, rather than ubiquitous, role in the immune landscape. ## Pathways and Molecular Function As a non-coding RNA, the precise molecular function of `[TNKS2 DT](/details-gene/100507633)` has not been fully characterized. However, its genomic organization as a divergent transcript from the promoter of the `[TNKS2](/details-gene/80351)` gene provides a strong basis for a potential *cis*-regulatory function. The neighboring `[TNKS2](/details-gene/80351)` gene encodes Tankyrase 2, a well-studied poly(ADP-ribose) polymerase. Tankyrases are involved in a multitude of cellular processes, most notably the regulation of Wnt/beta-catenin signaling ([R-HSA-195721](https://reactome.org/content/detail/R-HSA-195721)) by promoting the degradation of Axin, a key component of the beta-catenin destruction complex. Wnt signaling is critical for the maintenance and differentiation of stem cells, including neural and epidermal progenitors, which aligns with the observed expression pattern of `[TNKS2 DT](/details-gene/100507633)`. Additionally, `[TNKS2](/details-gene/80351)` is implicated in telomere length regulation ([GO:0000723](https://www.ebi.ac.uk/QuickGO/term/GO:0000723)), a process essential for the long-term proliferative capacity of stem cells. Therefore, it is plausible that `[TNKS2 DT](/details-gene/100507633)` acts locally to modulate `[TNKS2](/details-gene/80351)` expression, thereby fine-tuning these fundamental cellular pathways. ## Research Directions The specific expression pattern of `[TNKS2 DT](/details-gene/100507633)` in progenitor cells, combined with its potential link to the `[TNKS2](/details-gene/80351)`/Wnt signaling axis, opens several avenues for future investigation. **Testable Hypotheses:** 1. `[TNKS2 DT](/details-gene/100507633)` is essential for maintaining the proliferative, undifferentiated state of basal keratinocytes, and its targeted downregulation is a necessary trigger for terminal differentiation in the epidermis. 2. `[TNKS2 DT](/details-gene/100507633)` functions as a *cis*-acting lncRNA that positively regulates the transcription of `[TNKS2](/details-gene/80351)`, thereby enhancing Wnt signaling to support the self-renewal of `[neural progenitor cell](/details-cell/CL0011020)`s. 3. In `[CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)`s, `[TNKS2 DT](/details-gene/100507633)` expression contributes to the long-term survival and metabolic fitness required for memory cell maintenance. **Proposed Key Experiment:** To test the hypothesis that `[TNKS2 DT](/details-gene/100507633)` regulates epidermal differentiation (Hypothesis 1), a loss-of-function study could be performed using an organotypic skin model derived from primary human keratinocytes. Transcription of `[TNKS2 DT](/details-gene/100507633)` could be specifically suppressed using CRISPR interference (CRISPRi). The resulting 3D skin equivalents would then be analyzed by histology and immunofluorescence for markers of premature or aberrant differentiation (e.g., Keratin 10, Loricrin, Filaggrin). Concurrently, RNA-sequencing would reveal the global transcriptomic changes following `[TNKS2 DT](/details-gene/100507633)` knockdown, including the expression of `[TNKS2](/details-gene/80351)` and other Wnt pathway components. **Therapeutic Potential:** Given its high and specific expression in progenitor cells, `[TNKS2 DT](/details-gene/100507633)` could be a promising therapeutic target in hyperproliferative disorders, particularly cancers derived from these cell types like basal cell carcinoma. As a non-coding RNA, it is amenable to targeting via antisense oligonucleotides (ASOs) or siRNAs. An inhibitory strategy aimed at reducing `[TNKS2 DT](/details-gene/100507633)` levels could force malignant progenitor-like cells into a more differentiated, less proliferative state. The gene's low expression in terminally differentiated tissues suggests that such a therapy might have a favorable safety profile with minimal off-target effects.