Details for: DIO2 AS1

Gene ID: 100628307

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: DIO2 AS1

Ensembl ID: ENSG00000258766

Description: DIO2 antisense RNA 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Significant Cells

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

  • extravillous trophoblast CL0008036
    CSI 5.71
    rCSI 7.06%
    PRS 98.67
  • Mueller cell CL0000636
    CSI 3.17
    rCSI 7.23%
    PRS 97.87
  • basal cell CL0000646
    CSI 2.1
    rCSI 2.81%
    PRS 98.84
  • amacrine cell CL0000561
    CSI 2.09
    rCSI 6.05%
    PRS 97.21
  • GABAergic amacrine cell CL4030027
    CSI 1.34
    rCSI 4.57%
    PRS 95.51
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.43
    rCSI 10.48%
    PRS 95.52
  • ON midget ganglion cell CL4033046
    CSI 0.4
    rCSI 8.14%
    PRS 96.78

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

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  • 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 [DIO2 AS1](/details-gene/100628307) is a long non-coding RNA (lncRNA) located on chromosome 14. As an antisense transcript to the gene encoding iodothyronine deiodinase 2 (*DIO2*), its primary function is presumed to be the regulation of local thyroid hormone activation. Expression data indicates a highly specific role for [DIO2 AS1](/details-gene/100628307), with its significance being most pronounced in [extravillous trophoblast](/details-cell/CL0008036) of the placenta. It also shows notable significance in various cell types of the retina, including [Mueller cell](/details-cell/CL0000636) and [amacrine cell](/details-cell/CL0000561), suggesting a role in fine-tuning metabolic activity in specialized tissues critical for development and sensory function. ## Cellular Roles and Expression Landscape The expression profile of [DIO2 AS1](/details-gene/100628307) points to a highly specialized, context-dependent function rather than a ubiquitous housekeeping role. **Overall**, its most significant expression is observed in [extravillous trophoblast](/details-cell/CL0008036) (CSI: 5.71), a key cell type involved in placental implantation and maternal-fetal interface development. This strong association suggests a critical role in regulating placental function, potentially through modulating the local conversion of thyroid hormone necessary for a healthy pregnancy. A second major site of [DIO2 AS1](/details-gene/100628307) significance is the retina. It is a significant transcript in both glial and neuronal cells, including [Mueller cell](/details-cell/CL0000636) (CSI: 3.17), [amacrine cell](/details-cell/CL0000561) (CSI: 2.09), [GABAergic amacrine cell](/details-cell/CL4030027) (CSI: 1.34), and [ON midget ganglion cell](/details-cell/CL4033046) (CSI: 0.40). The presence in [Mueller cell](/details-cell/CL0000636), the principal glial cell of the retina, suggests a role in maintaining retinal homeostasis, while its expression in retinal neurons implies a potential function in neural processing and survival. Beyond these primary sites, [DIO2 AS1](/details-gene/100628307) also shows moderate significance in [basal cell](/details-cell/CL0000646) populations and lower, but still notable, significance in specific neuronal subtypes like the [indirect pathway medium spiny neuron](/details-cell/CL4023029) in the brain. This diverse but specific expression pattern is consistent with a role in regulating its target, *DIO2*, which is known to be crucial for local thyroid hormone activation in a tissue-specific manner. ## Pathways and Molecular Function While detailed functional annotations are not available, the identity of [DIO2 AS1](/details-gene/100628307) as an antisense non-coding RNA provides a strong hypothesis for its molecular function. It is likely involved in the regulation of *DIO2* gene expression, either through transcriptional interference, mRNA stability modulation, or chromatin remodeling. The primary pathway impacted by this regulation would be thyroid hormone metabolism. The *DIO2* enzyme catalyzes the conversion of the prohormone thyroxine (T4) into the biologically active triiodothyronine (T3). Therefore, [DIO2 AS1](/details-gene/100628307) is likely a key player in controlling the local availability of active T3. This function is highly consistent with its expression profile: * In **[extravillous trophoblast](/details-cell/CL0008036)**, precise T3 levels are critical for regulating proliferation, invasion, and vascular remodeling during placentation. * In the **retina**, local T3 is essential for the development, function, and maintenance of photoreceptors and other neurons. [DIO2 AS1](/details-eell/CL0000636)'s presence in [Mueller cell](/details-cell/CL0000636) suggests it may help control the metabolic support these glia provide to the surrounding neurons. ## Research Directions The specific expression pattern of [DIO2 AS1](/details-gene/100628307) suggests it is a fine-tuning regulator of a critical metabolic process in highly specialized cells. Future research should focus on elucidating its precise regulatory mechanism and its role in pathologies associated with these cell types. ### Proposed Testable Hypotheses 1. **[DIO2 AS1](/details-gene/100628307) acts as a negative regulator of *DIO2* expression in [extravillous trophoblast](/details-cell/CL0008036), and its downregulation is necessary for the increase in local T3 that promotes normal placental invasion. Dysregulation of this lncRNA may contribute to invasive placental disorders like preeclampsia or placenta accreta.** 2. **In the retina, [DIO2 AS1](/details-gene/100628307) functions as a homeostatic brake on T3 production within [Mueller cell](/details-cell/CL0000636), protecting neurons from metabolic over-activity. Pathological loss of [DIO2 AS1](/details-gene/100628307) could lead to metabolic stress and contribute to the progression of retinal degenerative diseases.** ### Suggested Experimental Approach To test the first hypothesis regarding the role of [DIO2 AS1](/details-gene/100628307) in [extravillous trophoblast](/details-cell/CL0008036) function, one could utilize an in vitro trophoblast cell line (e.g., HTR-8/SVneo). [DIO2 AS1](/details-gene/100628307) expression would be knocked down using sequence-specific antisense oligonucleotides (ASOs). The direct molecular consequences would be measured by quantifying *DIO2* mRNA and protein levels via qPCR and Western blotting, respectively. The functional impact would be assessed using a Matrigel transwell invasion assay to determine if loss of [DIO2 AS1](/details-gene/100628307) alters the invasive capacity of the cells, a key function of extravillous trophoblasts. ### Therapeutic Potential As a non-coding RNA with a highly restricted expression pattern, [DIO2 AS1](/details-gene/100628307) represents an attractive therapeutic target for nucleic acid-based drugs, such as ASOs. Such therapies could offer high specificity with potentially fewer off-target effects compared to small molecules targeting the ubiquitously important thyroid hormone system. Depending on whether it functions as a repressor or activator of *DIO2*, therapeutic intervention could aim to either inhibit [DIO2 AS1](/details-gene/100628307) to increase local T3 production or augment its function to reduce it. This could be particularly relevant in placental disorders where local metabolic and hormonal signaling is dysregulated.