Details for: HAGLR

Gene ID: 401022

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: HAGLR

Ensembl ID: ENSG00000224189

Description: HOXD antisense growth-associated long non-coding RNA

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Significant Cells

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

  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.2
    rCSI 8.12%
    PRS 96.85
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.19
    rCSI 3.07%
    PRS 97.79
  • epithelial cell of lung CL0000082
    CSI 3.17
    rCSI 2.63%
    PRS 98.89

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [HAGLR](/details-gene/401022) (HOXD Antisense Growth-Associated Long Non-Coding RNA) is a long non-coding RNA located on human chromosome 2q31.1. As its name suggests, it is transcribed antisense to the HOXD gene cluster, a family of homeobox genes critical for embryonic development and cellular differentiation. This genomic arrangement strongly implies a primary role for [HAGLR](/details-gene/401022) in the epigenetic and transcriptional regulation of these key developmental genes. Expression data highlights its significant and specific activity within various epithelial cell populations, including those of the kidney, fallopian tube, and lung, suggesting it is a key player in establishing or maintaining the specialized functions of these tissues. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [HAGLR](/details-gene/401022) indicates a highly specialized role within epithelial tissues. Its significance is most pronounced in: * [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 3.20) * [fallopian tube secretory epithelial cell](/details-cell/CL4030006) (CSI: 3.19) * [epithelial cell of lung](/details-cell/CL0000082) (CSI: 3.17) The consistent high significance of [HAGLR](/details-gene/401022) across these functionally diverse epithelial cells from different organ systems suggests a conserved role in fundamental epithelial biology. This may involve regulating pathways related to cellular adhesion, barrier function, secretion, or terminal differentiation, processes that are hallmarks of these cell types. The absence of data on its expression in non-epithelial lineages currently precludes a definitive statement on its absolute tissue specificity, but the available evidence points towards a focused function in epithelial cell identity and maintenance. ## Pathways and Molecular Function As a long non-coding RNA, [HAGLR](/details-gene/401022) is presumed to function as a molecular regulator rather than being translated into a protein. Its classification as a "HOXD antisense" transcript is the strongest indicator of its molecular function. It likely modulates the expression of adjacent HOXD genes through mechanisms such as transcriptional interference, recruitment of chromatin-modifying complexes (e.g., PRC2 or Trithorax-group proteins) to regulate the local chromatin state, or by altering the stability of HOXD mRNA transcripts. The "growth-associated" component of its name further suggests involvement in pathways controlling cell cycle progression, proliferation, or apoptosis, which are tightly linked to the developmental and homeostatic roles of the HOXD gene family. ## Research Directions Given the specificity of [HAGLR](/details-gene/401022) expression in epithelial cells and its putative regulatory relationship with the developmentally crucial HOXD gene cluster, its dysregulation is a plausible mechanism in epithelial diseases, particularly cancers (carcinomas). Here are several testable hypotheses: 1. **Hypothesis on Epithelial Differentiation:** We hypothesize that [HAGLR](/details-gene/401022) is a critical factor for maintaining the terminally differentiated state of specialized epithelial cells by precisely controlling the expression of one or more HOXD genes. Loss of [HAGLR](/details-gene/401022) would lead to aberrant HOXD expression, causing cellular de-differentiation and a loss of tissue-specific function. 2. **Hypothesis on Carcinogenesis:** We hypothesize that aberrant overexpression of [HAGLR](/details-gene/401022) in lung or kidney epithelial cells contributes to tumorigenesis by suppressing the expression of tumor-suppressive HOXD target genes, thereby promoting uncontrolled cell growth and proliferation. **Key Experimental Proposal:** To test the first hypothesis regarding the role of [HAGLR](/details-gene/401022) in epithelial maintenance, a targeted knockdown using locked nucleic acids (LNAs) or CRISPR interference (CRISPRi) could be performed in primary human fallopian tube secretory epithelial cells grown in an organoid culture. The effects on cell identity and function could be assessed using single-cell RNA sequencing (scRNA-seq) to map changes in differentiation trajectories and identify compensatory pathways. Concurrently, chromatin immunoprecipitation sequencing (ChIP-seq) for histone marks like H3K27me3 could determine if [HAGLR](/details-gene/401022) depletion alters the epigenetic landscape at the HOXD locus. **Therapeutic Potential:** The specific expression of [HAGLR](/details-gene/401022) in distinct epithelial lineages makes it an appealing therapeutic target, potentially offering a way to target disease pathways with fewer off-target effects. As a non-coding RNA, it is not amenable to small-molecule inhibitors targeting protein pockets. However, it is an excellent candidate for nucleic acid-based therapeutics. In cancers where [HAGLR](/details-gene/401022) is overexpressed and acts as an oncogene, **inhibition** via synthetic antisense oligonucleotides (ASOs) delivered systemically or locally could be a viable strategy to restore normal HOXD-mediated tumor suppression.