Details for: MS4A2

Gene ID: 2206

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MS4A2

Ensembl ID: ENSG00000149534

Description: membrane spanning 4-domains A2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • granulocyte CL0000094
    CSI 12.46
    rCSI 19.04%
    PRS 99.42
  • basophil CL0000767
    CSI 8.97
    rCSI 18.97%
    PRS 99.33
  • mast cell CL0000097
    CSI 8.16
    rCSI 17.62%
    PRS 95.49
  • basal cell of epidermis CL0002187
    CSI 7.41
    rCSI 13.14%
    PRS 90.32
  • melanocyte of skin CL1000458
    CSI 6.49
    rCSI 8.85%
    PRS 91.81
  • eosinophil CL0000771
    CSI 2.42
    rCSI 15.89%
    PRS 99.55

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [MS4A2](/details-gene/2206) (Membrane Spanning 4-Domains A2) encodes the beta subunit of the high-affinity immunoglobulin E (IgE) receptor, also known as Fc-epsilon RI-beta. This receptor complex is a critical component of the allergic and inflammatory response. The gene's primary function is integral to the `[Fc epsilon receptor (fceri) signaling](https://reactome.org/content/detail/R-HSA-2454202)` pathway, which is triggered upon IgE binding and antigen cross-linking. Consistent with this role, **Overall** expression analysis reveals that [MS4A2](/details-gene/2206) is a highly significant marker for key effector cells of the innate immune system, including [granulocytes](/details-cell/CL0000094), [basophils](/details-cell/CL0000767), and [mast cells](/details-cell/CL0000097). Genetic variants of [MS4A2](/details-gene/2206) have been associated with atopy and bronchial hyper-responsiveness, highlighting its clinical relevance in allergic diseases ([147138](https://omim.org/entry/147138)) as reported in several studies ([Link](https://doi.org/10.1093/hmg/5.7.959), [Link](https://doi.org/10.1093/hmg/5.8.1129)). ## Cellular Roles and Expression Landscape The expression profile of [MS4A2](/details-gene/2206) underscores its specialized function in allergic and anti-parasitic immunity. **Overall**, the gene shows the highest cell significance in [granulocytes](/details-cell/CL0000094) (CSI: 12.46), with particularly high specificity for [basophils](/details-cell/CL0000767) (CSI: 8.97) and [mast cells](/details-cell/CL0000097) (CSI: 8.16). These cells are the primary mediators of Type I hypersensitivity reactions, and the high expression of [MS4A2](/details-gene/2206) is essential for their function in assembling the high-affinity IgE receptor. Interestingly, significant expression is also noted in [basal cell of epidermis](/details-cell/CL0002187) (CSI: 7.41) and [melanocyte of skin](/details-cell/CL1000458) (CSI: 6.49). This suggests a potential, albeit less characterized, role for [MS4A2](/details-gene/2206)-mediated signaling in skin biology, possibly contributing to cutaneous allergic responses or other homeostatic processes within the epidermis. The gene's expression in [eosinophils](/details-cell/CL0000771) (CSI: 2.42), while lower, is also consistent with its involvement in allergic inflammation and host defense against parasites. The narrow and specific expression pattern emphasizes its role as a key component of a defined immunological pathway rather than a broadly expressed signaling molecule. ## Pathways and Molecular Function Functionally, [MS4A2](/details-gene/2206) is indispensable for the `[Immune response](https://www.ebi.ac.uk/QuickGO/term/GO:0006955)` ([GO:0006955](https://www.ebi.ac.uk/QuickGO/term/GO:0006955)), specifically through its role in the `[Cell surface receptor signaling pathway](https://www.ebi.ac.uk/QuickGO/term/GO:0007166)` ([GO:0007166](https://www.ebi.ac.uk/QuickGO/term/GO:0007166)). The encoded protein is a component of the `[Fc-epsilon receptor i complex](https://www.ebi.ac.uk/QuickGO/term/GO:0032998)` ([GO:0032998](https://www.ebi.ac.uk/QuickGO/term/GO:0032998)), located on the `[External side of plasma membrane](https://www.ebi.ac.uk/QuickGO/term/GO:0009897)` ([GO:0009897](https://www.ebi.ac.uk/QuickGO/term/GO:0009897)). Its primary molecular function involves `[Ige binding](https://www.ebi.ac.uk/QuickGO/term/GO:0019863)` ([GO:0019863](https://www.ebi.ac.uk/QuickGO/term/GO:0019863)) as part of the tetrameric receptor complex, which also includes alpha and two gamma subunits ([Link](https://doi.org/10.1016/s0021-9258(18)42344-7)). Activation of this receptor initiates a cascade of downstream events critical for cellular degranulation and the release of inflammatory mediators. Reactome pathways detail this process, including `[Fc epsilon receptor (fceri) signaling](https://reactome.org/content/detail/R-HSA-2454202)` ([R-HSA-2454202](https://reactome.org/content/detail/R-HSA-2454202)), leading to `[Fceri mediated ca+2 mobilization](https://reactome.org/content/detail/R-HSA-2871809)` ([R-HSA-2871809](https://reactome.org/content/detail/R-HSA-2871809)) and the activation of key transcription factors and signaling cascades such as `[Fceri mediated mapk activation](https://reactome.org/content/detail/R-HSA-2871796)` ([R-HSA-2871796](https://reactome.org/content/detail/R-HSA-2871796)) and `[Fceri mediated nf-kb activation](https://reactome.org/content/detail/R-HSA-2871837)` ([R-HSA-2871837](https://reactome.org/content/detail/R-HSA-2871837)). ## Research Directions While the role of [MS4A2](/details-gene/2206) in [mast cells](/details-cell/CL0000097) and [basophils](/details-cell/CL0000767) is well-established, several areas warrant further investigation. The notable expression in non-hematopoietic skin cells presents a key unanswered question. **Proposed Hypotheses:** 1. [MS4A2](/details-gene/2206) expression in [basal cells of the epidermis](/details-cell/CL0002187) and [melanocytes](/details-cell/CL1000458) contributes to the pathogenesis of cutaneous allergic reactions, such as atopic dermatitis, by enabling these cells to directly respond to IgE-allergen complexes and release pro-inflammatory mediators. 2. Genetic variants in [MS4A2](/details-gene/2206), such as the E237G polymorphism previously associated with atopy ([Link](https://doi.org/10.1093/hmg/5.7.959)), directly alter the signal amplification properties of the FcεRI complex in [basophils](/details-cell/CL0000767), leading to a lower threshold for degranulation and contributing to bronchial hyper-responsiveness. **Experimental Approach:** To test the first hypothesis regarding the function of [MS4A2](/details-gene/2206) in skin cells, a combination of *in situ* and *in vitro* approaches could be employed. Initially, spatial transcriptomics or high-plex immunofluorescence could be performed on skin biopsies from patients with atopic dermatitis and healthy controls to confirm and map the co-localization of [MS4A2](/details-gene/2206) protein, IgE, and inflammatory markers within the epidermis. Subsequently, primary human keratinocytes and melanocytes could be cultured and sensitized with patient-derived IgE, followed by stimulation with the relevant allergen. The functional consequences, such as calcium flux, cytokine/chemokine release (e.g., TSLP, IL-33), and changes in gene expression, could be measured by live-cell imaging, ELISA, and RNA-sequencing. CRISPR-Cas9-mediated knockout of [MS4A2](/details-gene/2206) in these primary cells would serve as a crucial control to establish a causal link between receptor expression and the observed functional responses. **Therapeutic Potential:** As a central component of the allergic cascade, the FcεRI complex, and by extension [MS4A2](/details-gene/2206), is a prime therapeutic target. Given its location on the plasma membrane and highly restricted expression pattern, it represents an attractive candidate for targeted inhibition to treat allergic diseases like asthma and atopic dermatitis. Therapeutic strategies could involve small molecule inhibitors designed to disrupt the assembly of the FcεRI complex or block its downstream signaling function. Furthermore, the development of monoclonal antibodies or other biologics that specifically target the [MS4A2](/details-gene/2206) subunit could offer a novel way to selectively dampen the activity of [mast cells](/details-cell/CL0000097) and [basophils](/details-cell/CL0000767) with potentially fewer off-target effects than broader immunosuppressants.

Genular Protein ID: 893552682

Symbol: FCERB_HUMAN

Name: High affinity immunoglobulin epsilon receptor subunit beta

UniProtKB Accession Codes:

Q01362 Q54A81

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 6 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 5 RefSeq 2 SIGNOR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 1535625

Title: The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor.

PubMed ID: 1535625

DOI: 10.1016/s0021-9258(18)42344-7

PubMed ID: 1386024

Title: Determination of the sequence coding for the beta subunit of the human high-affinity IgE receptor.

PubMed ID: 1386024

DOI: 10.1016/0014-5793(92)80430-o

PubMed ID: 12697656

Title: Regulation of human FcepsilonRI beta chain gene expression by Oct-1.

PubMed ID: 12697656

DOI: 10.1093/intimm/dxg055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8817330

Title: A new variant of the beta subunit of the high-affinity receptor for immunoglobulin E (Fc epsilon RI-beta E237G): associations with measures of atopy and bronchial hyper-responsiveness.

PubMed ID: 8817330

DOI: 10.1093/hmg/5.7.959

PubMed ID: 8842731

Title: Association between atopic asthma and a coding variant of Fc-epsilon-RI-beta in a Japanese population.

PubMed ID: 8842731

DOI: 10.1093/hmg/5.8.1129

PubMed ID: 8968765

Title:

PubMed ID: 8968765

Sequence Information:

  • Length: 244
  • Mass: 26534
  • Checksum: CE523102D5F567AF
  • Sequence:
    • MDTESNRRAN LALPQEPSSV PAFEVLEISP QEVSSGRLLK SASSPPLHTW LTVLKKEQEF 
LGVTQILTAM ICLCFGTVVC SVLDISHIEG DIFSSFKAGY PFWGAIFFSI SGMLSIISER 
RNATYLVRGS LGANTASSIA GGTGITILII NLKKSLAYIH IHSCQKFFET KCFMASFSTE 
IVVMMLFLTI LGLGSAVSLT ICGAGEELKG NKVPEDRVYE ELNIYSATYS ELEDPGEMSP 
PIDL

Genular Protein ID: 4271932181

Symbol: A0A0B4J2E9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0B4J2E9

Database IDs:

ARBA 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 1 GeneTree 1 HGNC 1 InterPro 2 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 RefSeq 1 SAM 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

Sequence Information:

  • Length: 199
  • Mass: 21650
  • Checksum: 28E1820359BE3616
  • Sequence:
    • MDTESNRRAN LALPQEPSSV PAFEVLEISP QEVSSGRLLK SASSPPLHTW LTVLKKEQEF 
LGFSISGMLS IISERRNATY LVRGSLGANT ASSIAGGTGI TILIINLKKS LAYIHIHSCQ 
KFFETKCFMA SFSTEIVVMM LFLTILGLGS AVSLTICGAG EELKGNKVPE DRVYEELNIY 
SATYSELEDP GEMSPPIDL