Details for: IGHA2

Gene ID: 3494

Gene Type:  Other  - A known gene or region type that lacks a specific category. Includes immunoglobulin (Ig), T-cell receptor (TCR) gene segments, and repetitive elements.

Symbol: IGHA2

Ensembl ID: ENSG00000211890

Description: immunoglobulin heavy constant alpha 2 (A2m marker)

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • IgA plasma cell CL0000987
    CSI 38.44
    rCSI 39.35%
    PRS 94.89
  • plasmablast CL0000980
    CSI 24.72
    rCSI 19.45%
    PRS 96.1
  • mononuclear phagocyte CL0000113
    CSI 11.47
    rCSI 25.26%
    PRS 96.93
  • colon epithelial cell CL0011108
    CSI 10.2
    rCSI 10.68%
    PRS 93.57
  • follicular B cell CL0000843
    CSI 9.38
    rCSI 34.09%
    PRS 98.19
  • intestine goblet cell CL0019031
    CSI 8.5
    rCSI 7.55%
    PRS 93.66
  • memory B cell CL0000787
    CSI 7.97
    rCSI 7.87%
    PRS 96.99
  • antibody secreting cell CL0000946
    CSI 7.65
    rCSI 34.02%
    PRS 99.25
  • CD4-positive helper T cell CL0000492
    CSI 6.02
    rCSI 4.55%
    PRS 99.21
  • transit amplifying cell CL0009010
    CSI 5.86
    rCSI 8.97%
    PRS 96.74
  • intestinal tuft cell CL0019032
    CSI 5.85
    rCSI 8.94%
    PRS 95.71
  • IgG plasma cell CL0000985
    CSI 5.85
    rCSI 7%
    PRS 96.44
  • class switched memory B cell CL0000972
    CSI 5.72
    rCSI 4.27%
    PRS 98.09
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 4.96
    rCSI 4.58%
    PRS 99
  • BEST4+ enteroycte CL4030026
    CSI 3.79
    rCSI 4.72%
    PRS 94.6
  • enteroendocrine cell CL0000164
    CSI 2.42
    rCSI 3.3%
    PRS 93.37
  • group 3 innate lymphoid cell CL0001071
    CSI 2.36
    rCSI 1.78%
    PRS 96.9
  • innate lymphoid cell CL0001065
    CSI 1.97
    rCSI 4.07%
    PRS 89.71
  • germinal center B cell CL0000844
    CSI 1.27
    rCSI 3.78%
    PRS 96.81

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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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 [IGHA2](/details-gene/3494) encodes the constant region of the heavy chain for immunoglobulin A2 (IgA2), a key antibody isotype involved in mucosal immunity. This gene is a central component of the humoral adaptive immune system, with its expression being a defining characteristic of antibody-secreting cells. **Overall**, data shows that [IGHA2](/details-gene/3494) has the highest significance in [IgA plasma cell](/details-cell/CL0000987) (CSI: 38.44) and [plasmablast](/details-cell/CL0000980) (CSI: 24.72), underscoring its role in the terminal differentiation of B lymphocytes and the production of IgA antibodies critical for immune defense at mucosal surfaces. ## Cellular Roles and Expression Landscape The expression profile of [IGHA2](/details-gene/3494) firmly establishes it as a specialist gene within the B cell lineage. Its paramount significance is observed in cells dedicated to antibody production, including [IgA plasma cell](/details-cell/CL0000987), [plasmablast](/details-cell/CL0000980), and [antibody secreting cell](/details-cell/CL0000946). The gene's activity is also significant, albeit at lower levels, in precursor B cell populations such as [follicular B cell](/details-cell/CL0000843), [memory B cell](/details-cell/CL0000787), and [class switched memory B cell](/details-cell/CL0000972), which is consistent with the process of B cell maturation and class-switch recombination leading to IgA production. Interestingly, [IGHA2](/details-gene/3494) also shows notable significance in non-lymphoid cell types associated with mucosal tissues, such as [colon epithelial cell](/details-cell/CL0011108) and [intestine goblet cell](/details-cell/CL0019031). This expression likely reflects the transcytosis of IgA via the polymeric immunoglobulin receptor (pIgR) to secrete it into the gut lumen, or potentially active uptake from the luminal environment. Furthermore, its relevance in [mononuclear phagocyte](/details-cell/CL0000113) suggests a role in IgA-mediated opsonization and phagocytosis, linking the humoral response to innate immune effector functions. ## Pathways and Molecular Function The function of [IGHA2](/details-gene/3494) is intrinsically linked to the adaptive immune response. Gene Ontology annotations highlight its central role in 'Adaptive immune response' ([GO:0002250](https://www.ebi.ac.uk/QuickGO/term/GO:0002250)) and the 'B cell receptor signaling pathway' ([GO:0050853](https://www.ebi.ac.uk/QuickGO/term/GO:0050853)). As a core component of the IgA2 antibody, its molecular function is defined by 'Antigen binding' ([GO:0003823](https://www.ebi.ac.uk/QuickGO/term/GO:0003823)) and 'Immunoglobulin receptor binding' ([GO:0034987](https://www.ebi.ac.uk/QuickGO/term/GO:0034987)), which enables it to neutralize pathogens and interact with Fc receptors on other immune cells. Cellular component annotations confirm that the protein product exists primarily in the 'Extracellular region' ([GO:0005576](https://www.ebi.ac.uk/QuickGO/term/GO:0005576)) and forms various immunoglobulin complexes, such as the 'Secretory dimeric iga immunoglobulin complex' ([GO:0071752](https://www.ebi.ac.uk/QuickGO/term/GO:0071752)), which is the predominant form at mucosal surfaces. Reactome pathways further connect IgA function to broader physiological processes, including 'Hemostasis' ([R-HSA-109582](https://reactome.org/content/detail/R-HSA-109582)) and 'Vesicle-mediated transport' ([R-HSA-5653656](https://reactome.org/content/detail/R-HSA-5653656)), the latter being consistent with the transcytosis of secretory IgA across epithelial barriers. ## Research Directions The expression data for [IGHA2](/details-gene/3494) prompts several lines of inquiry into the nuanced roles of IgA2 in immunity and tissue homeostasis. **Proposed Hypotheses:** 1. The significant expression score of [IGHA2](/details-gene/3494) in mucosal epithelial cells, such as [colon epithelial cell](/details-cell/CL0011108), is not merely a passive reflection of IgA transcytosis but indicates that these cells actively internalize and process IgA-antigen complexes from the gut lumen to regulate local inflammatory tone and barrier integrity. 2. The observed significance of [IGHA2](/details-gene/3494) in [mononuclear phagocyte](/details-cell/CL0000113) suggests that IgA2-mediated phagocytosis is a critical mechanism for clearing specific pathogens or cellular debris, and that defects in this pathway could contribute to chronic inflammatory conditions at mucosal sites. **Experimental Approach:** To test the first hypothesis regarding the active role of epithelial cells, one could utilize an intestinal organoid co-culture system. Organoids derived from human intestinal stem cells could be cultured with IgA2-secreting hybridomas or purified IgA2 complexed with a fluorescently-labeled antigen (e.g., a bacterial toxin). Confocal microscopy and live-cell imaging would be used to track the binding, internalization, and intracellular trafficking of IgA2 complexes within the epithelial cells. Subsequently, RNA-sequencing of the stimulated epithelial cells could identify downstream signaling pathways activated by IgA2 uptake, revealing its impact on cellular functions like tight junction gene expression and cytokine production. **Therapeutic Potential:** As [IGHA2](/details-gene/3494) encodes a part of a natural antibody, it is not a direct drug target for inhibition. Instead, its product, the IgA2 antibody, holds significant therapeutic promise. Engineering pathogen-specific monoclonal IgA2 antibodies could provide a powerful tool for passive immunization against mucosal pathogens (e.g., enteric bacteria or respiratory viruses), offering enhanced stability and function at mucosal surfaces compared to standard IgG-based therapies. Such a strategy would represent an activation or augmentation of a natural defense mechanism and could be particularly valuable for preventing infections in immunocompromised individuals or for treating antibiotic-resistant infections.