Details for: MS4A4A

Gene ID: 51338

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: MS4A4A

Ensembl ID: ENSG00000110079

Description: membrane spanning 4-domains A4A

Cell Significance Landscape

Associated with

Significant Cells

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

  • elicited macrophage CL0000861
    CSI 54.02
    rCSI 49.59%
    PRS 93.17
  • myeloid leukocyte CL0000766
    CSI 44.61
    rCSI 41.16%
    PRS 89.17
  • Hofbauer cell CL3000001
    CSI 38.33
    rCSI 72.37%
    PRS 93.36
  • alternatively activated macrophage CL0000890
    CSI 27.89
    rCSI 35.07%
    PRS 93.95
  • alveolar macrophage CL0000583
    CSI 25.67
    rCSI 42.28%
    PRS 90.34
  • macrophage CL0000235
    CSI 23.24
    rCSI 42.28%
    PRS 89.92
  • colon macrophage CL0009038
    CSI 14.11
    rCSI 65.19%
    PRS 95.43
  • Kupffer cell CL0000091
    CSI 11.21
    rCSI 25.62%
    PRS 89
  • non-classical monocyte CL0000875
    CSI 11.16
    rCSI 17.89%
    PRS 93.62
  • mononuclear phagocyte CL0000113
    CSI 10.65
    rCSI 23.45%
    PRS 90.73
  • lung macrophage CL1001603
    CSI 8.98
    rCSI 20.05%
    PRS 92.93
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 8.48
    rCSI 11.11%
    PRS 94.86
  • lung interstitial macrophage CL4033043
    CSI 7.34
    rCSI 16.47%
    PRS 95.79
  • neural progenitor cell CL0011020
    CSI 6.87
    rCSI 30.21%
    PRS 77.12
  • plasmacytoid dendritic cell, human CL0001058
    CSI 6.35
    rCSI 4.43%
    PRS 91.37
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 6.13
    rCSI 4.73%
    PRS 91.21
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 6.03
    rCSI 15.71%
    PRS 89.33
  • monocyte CL0000576
    CSI 5.64
    rCSI 10.2%
    PRS 89.97
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 5.1
    rCSI 6.16%
    PRS 93.37
  • common dendritic progenitor CL0001029
    CSI 4.79
    rCSI 6.01%
    PRS 93.75
  • inflammatory macrophage CL0000863
    CSI 4.64
    rCSI 7.92%
    PRS 96.46
  • tissue-resident macrophage CL0000864
    CSI 3.8
    rCSI 17.77%
    PRS 94.99
  • intermediate monocyte CL0002393
    CSI 3.55
    rCSI 5.36%
    PRS 92.24
  • promonocyte CL0000559
    CSI 3.49
    rCSI 5.98%
    PRS 91.14
  • dendritic cell, human CL0001056
    CSI 2.7
    rCSI 4.15%
    PRS 94
  • myeloid dendritic cell CL0000782
    CSI 2.44
    rCSI 3.53%
    PRS 96.08
  • promyelocyte CL0000836
    CSI 2.13
    rCSI 3.07%
    PRS 91.22
  • basal cell of epidermis CL0002187
    CSI 1.85
    rCSI 3.28%
    PRS 58.62
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 1.23
    rCSI 3.79%
    PRS 90.58
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 0.94
    rCSI 10.25%
    PRS 94.04
  • helper T cell CL0000912
    CSI 0.92
    rCSI 1.31%
    PRS 84.74
  • melanocyte of skin CL1000458
    CSI 0.86
    rCSI 1.17%
    PRS 57.65
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.85
    rCSI 1.03%
    PRS 68.74

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.

Comma-separated if multiple.
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 [MS4A4A](/details-gene/51338) (Membrane Spanning 4-Domains A4A) is a protein-coding gene located on chromosome 11q12.2. It is a member of the MS4A gene family, a group of four-transmembrane domain proteins that includes the well-characterized B-lymphocyte antigen CD20 ([Link](https://doi.org/10.1016/s0378-1119(00)00598-9)). While its precise molecular function remains under investigation, expression data strongly indicate a specialized role within the immune system. **Overall**, [MS4A4A](/details-gene/51338) serves as a highly significant marker for cells of the myeloid lineage, particularly the mononuclear phagocyte system, including various populations of [macrophages](/details-cell/CL0000235) and [monocytes](/details-cell/CL0000875). ## Cellular Roles and Expression Landscape The expression profile of [MS4A4A](/details-gene/51338) highlights its prominent role in myeloid cell identity and function. **Overall**, its expression is most significant in diverse macrophage populations, suggesting it is a core component of macrophage biology across different tissues and activation states. The top-ranking cell types for [MS4A4A](/details-gene/51338) significance are dominated by phagocytes: * **Top Markers:** It shows the highest significance in [elicited macrophage](/details-cell/CL0000861) (CSI: 54.02), the broad [myeloid leukocyte](/details-cell/CL0000766) category (CSI: 44.61), and specialized tissue-resident macrophages like placental [Hofbauer cell](/details-cell/CL3000001) (CSI: 38.33), [alveolar macrophage](/details-cell/CL0000583) (CSI: 25.67), [colon macrophage](/details-cell/CL0009038) (CSI: 14.11), and hepatic [Kupffer cell](/details-cell/CL0000091) (CSI: 11.21). * **Functional Subsets:** Its high significance in [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 27.89) suggests a potential role in M2-like polarization and anti-inflammatory responses. Its presence in [non-classical monocyte](/details-cell/CL0000875) (CSI: 11.16) and [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 6.35) further cements its identity as a marker of the mononuclear phagocyte system. Notably, a significant signal was also detected in [neural progenitor cell](/details-cell/CL0011020) (CSI: 6.87), which is inconsistent with the otherwise myeloid-restricted pattern. This suggests a potential, uncharacterized function for [MS4A4A](/details-gene/51338) outside of the immune system, possibly in neural development. ## Pathways and Molecular Function As a member of the MS4A family, [MS4A4A](/details-gene/51338) is structurally characterized as a protein with four transmembrane domains. Its cellular localization is consistent with this structure and its putative role in cell signaling. Gene Ontology annotations place it in the [plasma membrane](/details-cell/GO0005886), including specialized microdomains known as [plasma membrane raft](/details-cell/GO0044853). This localization is a common feature of MS4A proteins and suggests [MS4A4A](/details-gene/51338) may function as a scaffold or component of a larger signaling complex at the cell surface. Its presence is also noted in the [endoplasmic reticulum](/details-cell/GO0005783) and [Golgi apparatus](/details-cell/GO0005794), which reflects its transit through the secretory pathway during protein synthesis and trafficking. The annotated molecular function of [protein binding](/details-cell/GO0005515) is broad but aligns with the hypothesis that it acts as an adaptor or receptor component within a membrane-bound protein complex, potentially modulating intracellular signaling pathways in macrophages and other myeloid cells. ## Research Directions The specific expression of [MS4A4A](/details-gene/51338) in myeloid cells, particularly macrophages, positions it as an important gene for understanding myeloid biology in health and disease. Its structural similarity to CD20, a key regulator of B-cell signaling, provides a strong basis for future functional investigation. **Proposed Hypotheses:** 1. Given its high expression across diverse macrophage populations, including [alternatively activated macrophage](/details-cell/CL0000890), [MS4A4A](/details-gene/51338) may function as a surface receptor or channel component that regulates macrophage polarization, phagocytic activity, or cytokine release in response to environmental cues. 2. The unexpected expression of [MS4A4A](/details-gene/51338) in [neural progenitor cell](/details-cell/CL0011020) suggests a novel, non-immunological role. It could be involved in cell-cell communication, differentiation, or migration during neurogenesis. **Experimental Approach:** To test the first hypothesis regarding the role of [MS4A4A](/details-gene/51338) in macrophage function, a targeted gene-editing approach could be employed. Specifically, one could use CRISPR-Cas9 to knock out [MS4A4A](/details-gene/51338) in primary human [monocytes](/details-cell/CL0000875) or the THP-1 monocytic cell line. These knockout and wild-type control cells would then be differentiated into pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. The functional consequences of the knockout could be assessed by a multi-omics approach, including RNA-sequencing to measure changes in polarization-associated gene expression, multiplex ELISA or Luminex assays to quantify cytokine secretion profiles, and functional assays to measure phagocytic capacity. **Therapeutic Potential:** As a cell surface protein highly enriched on macrophages, [MS4A4A](/details-gene/51338) presents a promising therapeutic target. Its myeloid-specific expression profile suggests that targeting it would have minimal off-target effects on other major cell lineages. Depending on its function, it could be targeted for either inhibition or activation. If [MS4A4A](/details-gene/51338) is found to promote pro-tumorigenic or pro-inflammatory macrophage activity, an inhibitory monoclonal antibody or antibody-drug conjugate could be developed for use in oncology or autoimmune disorders. Conversely, if it promotes regenerative or anti-inflammatory functions, an agonistic antibody could be explored as a therapy to enhance tissue repair or resolve inflammation.

Genular Protein ID: 3912689953

Symbol: M4A4A_HUMAN

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

UniProtKB Accession Codes:

Q96JQ5 Q8TEZ6 Q96PG7 Q9BY18 Q9H3V3 Q9P1S3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 4 GeneCards 1 GeneTree 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 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 4 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 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: 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: 11486273

Title: Structural organization of the human MS4A gene cluster on chromosome 11q12.

PubMed ID: 11486273

DOI: 10.1007/s002510100339

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: 239
  • Mass: 25441
  • Checksum: F0617D94669CB447
  • Sequence:
    • MHQTYSRHCR PEESTFSAAM TTMQGMEQAM PGAGPGVPQL GNMAVIHSHL WKGLQEKFLK 
GEPKVLGVVQ ILTALMSLSM GITMMCMASN TYGSNPISVY IGYTIWGSVM FIISGSLSIA 
AGIRTTKGLV RGSLGMNITS SVLAASGILI NTFSLAFYSF HHPYCNYYGN SNNCHGTMSI 
LMGLDGMVLL LSVLEFCIAV SLSAFGCKVL CCTPGGVVLI LPSHSHMAET ASPTPLNEV

Genular Protein ID: 1090508247

Symbol: Q4JF27_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q4JF27

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1

Citations:

PubMed ID: 16303743

Title: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

PubMed ID: 16303743

DOI: 10.1093/dnares/12.2.117

Sequence Information:

  • Length: 220
  • Mass: 23170
  • Checksum: 620D5FD6435B48F1
  • Sequence:
    • MTTMQGMEQA MPGAGPGVPQ LGNMAVIHSH LWKGLQEKFL KGEPKVLGVV QILTALMSLS 
MGITMMCMAS NTYGSNPISA YIGYTIWGSV MFIISGSLPI AAGIRTTKGL VRGSLGMNIT 
SSVLAASGIL INTFSLAFYS FHHPYCNYYG NSNNCHGTVS ILMGLDGMVL LLSVLEFCIA 
VSLSAFGCKV LCCTPGGVVL ILPSHSHMAE TASPTPLNEV

Genular Protein ID: 1218743821

Symbol: A0A384MDW1_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A384MDW1

Database IDs:

ARBA 1 Antibodypedia 1 Bgee 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 GO 1 GeneTree 1 HGNC 1 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 Proteomes 2 RefSeq 2 SAM 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

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: 220
  • Mass: 23220
  • Checksum: 7648C762197C1179
  • Sequence:
    • MTTMQGMEQA MPGAGPGVPQ LGNMAVIHSH LWKGLQEKFL KGEPKVLGVV QILTALMSLS 
MGITMMCMAS NTYGSNPISV YIGYTIWGSV MFIISGSLSI AAGIRTTKGL VRGSLGMNIT 
SSVLAASGIL INTFSLAFYS FHHPYCNYYG NSNNCHGTMS ILMGLDGMVL LLSVLEFCIA 
VSLSAFGCKV LCCTPGGVVL ILPSHSHMAE TASPTPLNEV