Details for: MS4A7

Gene ID: 58475

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: MS4A7

Ensembl ID: ENSG00000166927

Description: membrane spanning 4-domains A7

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 71.53
    rCSI 55.11%
    PRS 93.82
  • elicited macrophage CL0000861
    CSI 54.53
    rCSI 50.07%
    PRS 95.01
  • Kupffer cell CL0000091
    CSI 32.75
    rCSI 74.89%
    PRS 91.95
  • non-classical monocyte CL0000875
    CSI 32.71
    rCSI 52.43%
    PRS 95.38
  • alveolar macrophage CL0000583
    CSI 31.26
    rCSI 51.49%
    PRS 92.71
  • myeloid leukocyte CL0000766
    CSI 29.27
    rCSI 27.01%
    PRS 92.11
  • alternatively activated macrophage CL0000890
    CSI 27.64
    rCSI 34.75%
    PRS 95.74
  • plasmacytoid dendritic cell, human CL0001058
    CSI 18.86
    rCSI 13.17%
    PRS 93.92
  • lung macrophage CL1001603
    CSI 18.72
    rCSI 41.82%
    PRS 95.01
  • macrophage CL0000235
    CSI 18.35
    rCSI 33.38%
    PRS 91.61
  • CD14-positive monocyte CL0001054
    CSI 17.69
    rCSI 22.04%
    PRS 95.95
  • mononuclear phagocyte CL0000113
    CSI 17.45
    rCSI 38.42%
    PRS 93.26
  • lung interstitial macrophage CL4033043
    CSI 17.02
    rCSI 38.2%
    PRS 97.15
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 16.89
    rCSI 22.13%
    PRS 96.34
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 12.83
    rCSI 33.45%
    PRS 92.38
  • colon macrophage CL0009038
    CSI 12.42
    rCSI 57.38%
    PRS 96.59
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 12.3
    rCSI 14.85%
    PRS 95.15
  • conventional dendritic cell CL0000990
    CSI 11.31
    rCSI 9.44%
    PRS 86
  • inflammatory macrophage CL0000863
    CSI 10.49
    rCSI 17.93%
    PRS 97.46
  • dendritic cell CL0000451
    CSI 9.61
    rCSI 11.84%
    PRS 90.65
  • monocyte CL0000576
    CSI 8.88
    rCSI 16.04%
    PRS 92.2
  • microglial cell CL0000129
    CSI 8.67
    rCSI 34.88%
    PRS 89.54
  • intermediate monocyte CL0002393
    CSI 8.23
    rCSI 12.42%
    PRS 94.68
  • Langerhans cell CL0000453
    CSI 7.67
    rCSI 11.71%
    PRS 96.17
  • tissue-resident macrophage CL0000864
    CSI 4.93
    rCSI 23.1%
    PRS 96.66
  • granulocyte monocyte progenitor cell CL0000557
    CSI 4.2
    rCSI 3.64%
    PRS 93.06
  • professional antigen presenting cell CL0000145
    CSI 3.87
    rCSI 13.32%
    PRS 94.45
  • myeloid dendritic cell CL0000782
    CSI 3.48
    rCSI 5.05%
    PRS 97.4
  • mature NK T cell CL0000814
    CSI 3.04
    rCSI 3.89%
    PRS 94.75
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 2.78
    rCSI 16.83%
    PRS 95.75
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 2.69
    rCSI 29.21%
    PRS 95.88
  • promyelocyte CL0000836
    CSI 2.34
    rCSI 3.37%
    PRS 93.01
  • transitional stage B cell CL0000818
    CSI 1.4
    rCSI 4.58%
    PRS 97.4
  • dendritic cell, human CL0001056
    CSI 1.32
    rCSI 2.03%
    PRS 95.78
  • myeloid dendritic cell, human CL0001057
    CSI 1.05
    rCSI 5.92%
    PRS 97.2
  • kidney resident macrophage CL1000698
    CSI 0.66
    rCSI 13.1%
    PRS 96.8

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 [MS4A7](/details-gene/58475) (Membrane Spanning 4-Domains A7) is a protein-coding gene located on chromosome 11q12.2. It belongs to the MS4A gene family, which also includes the well-known B-lymphocyte antigen CD20 ([Link](https://doi.org/10.1016/s0378-1119(00)00598-9), [Link](https://doi.org/10.1006/geno.2000.6472)). Functionally, [MS4A7](/details-gene/58475) is annotated as a plasma membrane protein involved in cell surface receptor signaling. Expression data highlights its highly specific and abundant role within the myeloid compartment of the immune system, where it serves as a key marker for various monocyte and macrophage populations. ## Cellular Roles and Expression Landscape The expression profile of [MS4A7](/details-gene/58475) firmly establishes it as a specialist gene within the innate immune system, particularly in cells of the mononuclear phagocyte lineage. **Overall**, the gene shows its most significant expression in [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) (CSI: 71.53), suggesting it is a defining marker for this specific monocyte subset. Its high significance extends broadly across various macrophage types, including [elicited macrophages](/details-cell/CL0000861) (CSI: 54.53) and tissue-resident macrophages such as [Kupffer cells](/details-cell/CL0000091) in the liver (CSI: 32.75) and [alveolar macrophages](/details-cell/CL0000583) in the lung (CSI: 31.26). The gene is also a prominent marker in [non-classical monocytes](/details-cell/CL0000875), [alternatively activated macrophages](/details-cell/CL0000890), and [plasmacytoid dendritic cells](/details-cell/CL0001058), underscoring its widespread importance within myeloid cell biology. The consistently high CSI scores across these related cell types indicate that [MS4A7](/details-gene/58475) is not only a specific marker but also likely a crucial functional component for these cells. ## Pathways and Molecular Function Functional annotations are consistent with the gene's cellular expression pattern. As a component of the [plasma membrane](/details-cell/GO:0005886) and the [trans-Golgi network](/details-cell/GO:0005802), [MS4A7](/details-gene/58475) is positioned to participate in transmembrane signaling. Its involvement in the [cell surface receptor signaling pathway](/details-cell/GO:0007166) suggests a role in how monocytes and macrophages sense and respond to their microenvironment. Furthermore, its predicted [protein binding](/details-cell/GO:0005515) capability implies it may function as part of a larger protein complex, similar to other MS4A family members, to mediate downstream cellular responses. This molecular function is critical for the immunological activities of macrophages and monocytes, such as phagocytosis, antigen presentation, and cytokine secretion. ## Research Directions The highly specific expression of [MS4A7](/details-gene/58475) in myeloid cells, particularly macrophages and monocytes, provides a clear basis for further investigation into its role in immunity and disease. Based on the available data, several testable hypotheses can be proposed: 1. Given its high expression in diverse tissue-resident macrophages ([Kupffer cells](/details-cell/CL0000091), [alveolar macrophages](/details-cell/CL0000583)), [MS4A7](/details-gene/58475) may regulate tissue-specific macrophage functions, such as metabolic homeostasis in the liver or pathogen clearance in the lungs. 2. The high significance of [MS4A7](/details-gene/58475) in both patrolling [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) and pro-inflammatory [CD14-positive, CD16-positive monocytes](/details-cell/CL0002397) suggests it may be involved in modulating monocyte inflammatory responses and their subsequent differentiation upon entering tissues during an immune challenge. A key experiment to test the first hypothesis would be to use a conditional knockout mouse model to specifically delete *Ms4a7* in myeloid cells (e.g., using a LysM-Cre driver). One could then isolate primary [Kupffer cells](/details-cell/CL0000091) from both knockout and wild-type mice and perform *in vitro* functional assays. For example, a phagocytosis assay using fluorescently labeled E. coli could quantify the cells' engulfment capacity, while stimulation with lipopolysaccharide (LPS) followed by RNA-sequencing or cytokine profiling (ELISA) would reveal the role of [MS4A7](/details-gene/58475) in the inflammatory response pathway. As a potential therapeutic target, [MS4A7](/details-gene/58475) is promising due to its specific expression on the surface of myeloid cells. In diseases characterized by pathological macrophage activity, such as certain solid tumors (where tumor-associated macrophages promote growth) or fibrotic diseases, targeting [MS4A7](/details-gene/58475) could allow for the specific depletion or modulation of these cells. A therapeutic strategy involving inhibition, likely through an antibody-drug conjugate (ADC) or a monoclonal antibody designed to induce antibody-dependent cell-mediated cytotoxicity (ADCC), could be envisioned to eliminate disease-promoting macrophage populations with minimal off-target effects on other cell lineages.

Genular Protein ID: 1754503197

Symbol: MS4A7_HUMAN

Name: Membrane-spanning 4-domains subfamily A member 7

UniProtKB Accession Codes:

Q9GZW8 A6NP53 Q6IAG8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 3 ExpressionAtlas 1 GO 3 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 NIAGADS 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 4 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11245982

Title: Identification of a new multigene four-transmembrane family (MS4A) related to CD20, HTm4 and beta subunit of the high-affinity IgE receptor.

PubMed ID: 11245982

DOI: 10.1016/s0378-1119(00)00598-9

PubMed ID: 11685457

Title: CFFM4: a new member of the CD20/Fc-epsilon-RI-beta-family.

PubMed ID: 11685457

DOI: 10.1007/s002510100345

PubMed ID: 11401424

Title: Identification of a CD20-, Fc-epsilon-RI-beta-, and HTm4-related gene family: sixteen new MS4A family members expressed in human and mouse.

PubMed ID: 11401424

DOI: 10.1006/geno.2000.6472

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

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

PubMed ID: 16554811

DOI: 10.1038/nature04632

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

Sequence Information:

  • Length: 240
  • Mass: 26131
  • Checksum: 512BC9C126C76DC0
  • Sequence:
    • MLLQSQTMGV SHSFTPKGIT IPQREKPGHM YQNEDYLQNG LPTETTVLGT VQILCCLLIS 
SLGAILVFAP YPSHFNPAIS TTLMSGYPFL GALCFGITGS LSIISGKQST KPFDLSSLTS 
NAVSSVTAGA GLFLLADSMV ALRTASQHCG SEMDYLSSLP YSEYYYPIYE IKDCLLTSVS 
LTGVLVVMLI FTVLELLLAA YSSVFWWKQL YSNNPGSSFS STQSQDHIQQ VKKSSSRSWI