Details for: IGHV4 30 2

Gene ID: 28398

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: IGHV4 30 2

Ensembl ID: ENSG00000231475

Description: immunoglobulin heavy variable 4-30-2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Significant Cells

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

  • IgA plasma cell CL0000987
    CSI 9.34
    rCSI 9.57%
    PRS 98.84
  • IgG plasma cell CL0000985
    CSI 5.34
    rCSI 6.4%
    PRS 99.48
  • plasmablast CL0000980
    CSI 4.37
    rCSI 3.44%
    PRS 99.45

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 Immunoglobulin heavy variable 4-30-2, encoded by the [IGHV4 30 2](/details-gene/28398) gene, is a variable (V) segment of the immunoglobulin heavy chain locus on chromosome 14. This gene is a critical component for generating the vast diversity of antigen-binding sites on B-cell receptors and secreted antibodies. Its expression is highly restricted to the B-lymphocyte lineage, with data indicating it is a significant molecular feature of terminally differentiated, antibody-secreting cells. Specifically, it shows high significance in [IgA plasma cells](/details-cell/CL0000987), [IgG plasma cells](/details-cell/CL0000985), and [plasmablasts](/details-cell/CL0000980), underscoring its essential role in the effector phase of the humoral immune response. ## Cellular Roles and Expression Landscape The expression profile of [IGHV4 30 2](/details-gene/28398) is tightly regulated and specific to mature B-lineage cells committed to antibody production. **Overall**, the gene demonstrates its highest significance in cells that constitute the primary secretors of immunoglobulins. The top-ranked cell types include [IgA plasma cells](/details-cell/CL0000987) (CSI: 9.34), [IgG plasma cells](/details-cell/CL0000985) (CSI: 5.34), and their immediate precursors, [plasmablasts](/details-cell/CL0000980) (CSI: 4.37). This pattern suggests that the transcriptional activity of the [IGHV4 30 2](/details-gene/28398) locus is a defining characteristic of the terminal differentiation program that transforms activated B-cells into professional antibody-secreting factories. The presence of this V-gene transcript is a direct indicator of an active humoral immune response within a tissue. ## Pathways and Molecular Function As a structural gene segment, [IGHV4 30 2](/details-gene/28398) does not directly participate in enzymatic or signaling cascades but is fundamental to the molecular function of antigen recognition. Its primary role is to encode a portion of the variable domain that forms the antigen-binding site (paratope) of an antibody molecule. The gene segment is assembled with D (Diversity) and J (Joining) segments during somatic [V(D)J recombination](https://reactome.org/content/detail/R-HSA-975956) in developing B-cells, a process central to generating a diverse antibody repertoire. Consequently, [IGHV4 30 2](/details-gene/28398) is a key component in the broader biological processes of the [adaptive immune response](https://www.ebi.ac.uk/QuickGO/term/GO:0002250) and, more specifically, the [humoral immune response](https://www.ebi.ac.uk/QuickGO/term/GO:0002455). ## Research Directions The specific usage of particular IGHV gene segments in disease states is an area of active investigation, with implications for understanding autoimmunity, infection, and B-cell malignancies. ### Proposed Hypotheses: 1. **Role in Autoimmunity:** In certain autoimmune conditions, such as systemic lupus erythematosus or rheumatoid arthritis, pathogenic autoantibodies may exhibit a biased, non-random usage of the [IGHV4 30 2](/details-gene/28398) gene segment, suggesting it contributes a structural motif favorable for binding to self-antigens. 2. **Marker for B-cell Malignancy:** The clonal expansion of a malignant B-cell population in diseases like multiple myeloma or chronic lymphocytic leukemia could lead to the overexpression of a single, rearranged IGHV gene, such as [IGHV4 30 2](/details-gene/28398). This clonal transcript could serve as a highly specific biomarker for monitoring minimal residual disease (MRD). ### Key Experimental Approach: To test the hypothesis regarding its role in autoimmunity, a powerful approach would be to perform single-cell V(D)J sequencing (sc-V(D)J-seq) on sorted [plasma cells](/details-cell/CL0000987) and [plasmablasts](/details-cell/CL0000980) from the peripheral blood or affected tissues of patients and healthy controls. This would enable a direct, quantitative comparison of [IGHV4 30 2](/details-gene/28398) usage frequency within the antibody repertoires and allow for the identification of expanded, potentially pathogenic, B-cell clones that preferentially utilize this gene segment. ### Therapeutic Potential: [IGHV4 30 2](/details-gene/28398) itself is not a conventional drug target. However, the unique antigen-binding site (idiotype) that it helps form on a clonal B-cell population represents a highly specific tumor antigen. In the context of B-cell cancers, therapies could be designed to target this idiotype. This could include patient-specific CAR-T cells engineered to recognize the unique B-cell receptor, or the development of anti-idiotype antibodies. Such an approach would represent a form of personalized medicine, aiming for the targeted elimination of the malignant clone while sparing healthy B-cells.