Details for: FCER1G

Gene ID: 2207

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: FCER1G

Ensembl ID: ENSG00000158869

Description: Fc epsilon receptor Ig

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 100.59
    rCSI 77.5%
    PRS 97.17
  • elicited macrophage CL0000861
    CSI 90.08
    rCSI 82.71%
    PRS 97.71
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 84.76
    rCSI 56.49%
    PRS 97.65
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 79
    rCSI 59.24%
    PRS 98.45
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 64.44
    rCSI 84.43%
    PRS 98.45
  • myeloid leukocyte CL0000766
    CSI 62.8
    rCSI 57.94%
    PRS 95.94
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 61.16
    rCSI 73.87%
    PRS 97.66
  • alternatively activated macrophage CL0000890
    CSI 51.22
    rCSI 64.4%
    PRS 98.16
  • plasmacytoid dendritic cell, human CL0001058
    CSI 50.07
    rCSI 34.96%
    PRS 96.91
  • non-classical monocyte CL0000875
    CSI 46.21
    rCSI 74.07%
    PRS 97.63
  • activated type II NK T cell CL0000931
    CSI 45.65
    rCSI 51.38%
    PRS 98.38
  • CD14-positive monocyte CL0001054
    CSI 43.36
    rCSI 54%
    PRS 98.21
  • promonocyte CL0000559
    CSI 42.88
    rCSI 73.46%
    PRS 95.89
  • Hofbauer cell CL3000001
    CSI 42.12
    rCSI 79.51%
    PRS 97.64
  • intermediate monocyte CL0002393
    CSI 41.65
    rCSI 62.85%
    PRS 97.58
  • classical monocyte CL0000860
    CSI 41.33
    rCSI 61.27%
    PRS 96.93
  • alveolar macrophage CL0000583
    CSI 38.61
    rCSI 63.6%
    PRS 96
  • myeloid dendritic cell CL0000782
    CSI 31.07
    rCSI 45.01%
    PRS 98.86
  • group 3 innate lymphoid cell CL0001071
    CSI 30.83
    rCSI 23.16%
    PRS 96.66
  • monocyte CL0000576
    CSI 30.19
    rCSI 54.58%
    PRS 95.77
  • Kupffer cell CL0000091
    CSI 29.61
    rCSI 67.72%
    PRS 95.83
  • dendritic cell CL0000451
    CSI 28.89
    rCSI 35.6%
    PRS 94.17
  • mononuclear phagocyte CL0000113
    CSI 28.82
    rCSI 63.43%
    PRS 96.65
  • inflammatory macrophage CL0000863
    CSI 28.36
    rCSI 48.46%
    PRS 99.11
  • lung macrophage CL1001603
    CSI 28.3
    rCSI 63.21%
    PRS 97.88
  • plasmacytoid dendritic cell CL0000784
    CSI 27.56
    rCSI 27.92%
    PRS 97.67
  • macrophage CL0000235
    CSI 26.82
    rCSI 48.79%
    PRS 94.92
  • granulocyte monocyte progenitor cell CL0000557
    CSI 26
    rCSI 22.52%
    PRS 96.06
  • intraepithelial lymphocyte CL0002496
    CSI 25.92
    rCSI 70.55%
    PRS 98.5
  • conventional dendritic cell CL0000990
    CSI 25.59
    rCSI 21.36%
    PRS 89.2
  • Langerhans cell CL0000453
    CSI 25.47
    rCSI 38.9%
    PRS 98.2
  • mature NK T cell CL0000814
    CSI 24.99
    rCSI 31.97%
    PRS 96.84
  • natural killer cell CL0000623
    CSI 24.66
    rCSI 47.79%
    PRS 94.38
  • dendritic cell, human CL0001056
    CSI 23.96
    rCSI 36.8%
    PRS 98.06
  • hematopoietic stem cell CL0000037
    CSI 22.96
    rCSI 15.26%
    PRS 95.8
  • common dendritic progenitor CL0001029
    CSI 22.15
    rCSI 27.8%
    PRS 97.55
  • fibroblast of lung CL0002553
    CSI 21.14
    rCSI 19.68%
    PRS 96
  • myeloid cell CL0000763
    CSI 20.41
    rCSI 84.05%
    PRS 96.13
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 20.34
    rCSI 24.28%
    PRS 98.59
  • mature T cell CL0002419
    CSI 19.71
    rCSI 15.33%
    PRS 98.68
  • erythrocyte CL0000232
    CSI 18.88
    rCSI 42.83%
    PRS 93.19
  • promyelocyte CL0000836
    CSI 18.75
    rCSI 27.04%
    PRS 95.84
  • innate lymphoid cell CL0001065
    CSI 18.75
    rCSI 38.7%
    PRS 89.33
  • granulocyte CL0000094
    CSI 18.43
    rCSI 28.15%
    PRS 97.31
  • basophil CL0000767
    CSI 17.81
    rCSI 37.69%
    PRS 97.3
  • mast cell CL0000097
    CSI 17.75
    rCSI 38.33%
    PRS 92
  • common myeloid progenitor CL0000049
    CSI 16.53
    rCSI 13.37%
    PRS 95.78
  • professional antigen presenting cell CL0000145
    CSI 16.31
    rCSI 56.17%
    PRS 96.19
  • colon macrophage CL0009038
    CSI 16.13
    rCSI 74.51%
    PRS 98.57
  • lung interstitial macrophage CL4033043
    CSI 15.99
    rCSI 35.9%
    PRS 98.82
  • glial cell CL0000125
    CSI 15.85
    rCSI 60.35%
    PRS 90.22
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 15.55
    rCSI 11.83%
    PRS 99.01
  • early lymphoid progenitor CL0000936
    CSI 15.31
    rCSI 13.45%
    PRS 96.99
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 14.59
    rCSI 13.17%
    PRS 94.34
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 13.39
    rCSI 81.01%
    PRS 97.95
  • megakaryocyte CL0000556
    CSI 13.29
    rCSI 57.65%
    PRS 94.86
  • platelet CL0000233
    CSI 12.66
    rCSI 52.52%
    PRS 91.17
  • myeloid dendritic cell, human CL0001057
    CSI 12.36
    rCSI 69.58%
    PRS 98.78
  • bronchus fibroblast of lung CL2000093
    CSI 11.93
    rCSI 9.7%
    PRS 94.71
  • epithelial cell of lower respiratory tract CL0002632
    CSI 11.45
    rCSI 8.88%
    PRS 96.52
  • memory T cell CL0000813
    CSI 11.27
    rCSI 21.71%
    PRS 98.74
  • neutrophil CL0000775
    CSI 10.82
    rCSI 60.54%
    PRS 92.56
  • microglial cell CL0000129
    CSI 10.81
    rCSI 43.53%
    PRS 93.79
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 9.83
    rCSI 25.63%
    PRS 96.28
  • alveolar adventitial fibroblast CL4028006
    CSI 9.18
    rCSI 14.5%
    PRS 95.74
  • vascular associated smooth muscle cell CL0000359
    CSI 8.99
    rCSI 29.16%
    PRS 93.91
  • intrahepatic cholangiocyte CL0002538
    CSI 8.95
    rCSI 21.48%
    PRS 94.48
  • tissue-resident macrophage CL0000864
    CSI 8.88
    rCSI 41.55%
    PRS 98.58
  • myelocyte CL0002193
    CSI 8.27
    rCSI 54.32%
    PRS 97.74
  • multi-ciliated epithelial cell CL0005012
    CSI 8.03
    rCSI 8.01%
    PRS 90.82
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 6.44
    rCSI 70%
    PRS 98.16
  • lung ciliated cell CL1000271
    CSI 6.25
    rCSI 7.22%
    PRS 91.11
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 5.81
    rCSI 17.89%
    PRS 95.8
  • mature B cell CL0000785
    CSI 5.46
    rCSI 4.75%
    PRS 98.15
  • plasmablast CL0000980
    CSI 4.94
    rCSI 3.89%
    PRS 95.81
  • decidual natural killer cell, human CL0002343
    CSI 4.91
    rCSI 49.88%
    PRS 97.11
  • common lymphoid progenitor CL0000051
    CSI 4.87
    rCSI 6.51%
    PRS 98.7
  • alpha-beta T cell CL0000789
    CSI 4.49
    rCSI 5.26%
    PRS 98.5
  • epithelial cell of lung CL0000082
    CSI 3.66
    rCSI 3.04%
    PRS 95.86
  • group 2 innate lymphoid cell CL0001069
    CSI 3.29
    rCSI 17.81%
    PRS 98.59
  • fraction A pre-pro B cell CL0002045
    CSI 3.29
    rCSI 3.76%
    PRS 96.79
  • eosinophil CL0000771
    CSI 3.17
    rCSI 20.78%
    PRS 98.37
  • pre-conventional dendritic cell CL0002010
    CSI 3.14
    rCSI 41.55%
    PRS 98.62
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 3.11
    rCSI 15.59%
    PRS 98.51
  • exhausted T cell CL0011025
    CSI 2.47
    rCSI 41.81%
    PRS 96.24
  • kidney resident macrophage CL1000698
    CSI 2.35
    rCSI 46.91%
    PRS 98.63
  • CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074
    CSI 1.9
    rCSI 22.1%
    PRS 98.26
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.69
    rCSI 8.72%
    PRS 98.73
  • erythroid progenitor cell CL0000038
    CSI 1.29
    rCSI 7.4%
    PRS 95.98
  • cord blood hematopoietic stem cell CL2000095
    CSI 1.22
    rCSI 23.5%
    PRS 96.04
  • group 3 innate lymphoid cell, human CL0001078
    CSI 1.09
    rCSI 23.06%
    PRS 96.89
  • immature innate lymphoid cell CL0001082
    CSI 0.81
    rCSI 25.19%
    PRS 99.67
  • megakaryocyte progenitor cell CL0000553
    CSI 0.28
    rCSI 5.04%
    PRS 99.05

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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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 [FCER1G](/details-gene/2207), or Fc Epsilon Receptor Ig, encodes the common gamma chain (γ-chain), a critical signal-transducing subunit for a variety of immune cell receptors, including the high-affinity IgE receptor (FcεRI) and several IgG Fc receptors (FcγRs). Its expression is predominantly localized to hematopoietic cells, particularly those of the myeloid and lymphoid lineages. Data from the **Overall** context show its highest significance in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396), [elicited macrophage](/details-cell/CL0000861), and [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939). As an essential component for receptor assembly and function [Link](https://pubmed.ncbi.nlm.nih.gov/8611682/), [FCER1G](/details-gene/2207) plays a central role in translating antibody-antigen complex recognition into downstream cellular responses such as phagocytosis, degranulation, and cytokine production, linking the adaptive and innate immune systems. Its clinical relevance is underscored by its association with immune system functions documented in OMIM ([147139](https://omim.org/entry/147139)). ## Cellular Roles and Expression Landscape The expression pattern of [FCER1G](/details-gene/2207) firmly establishes its importance within the innate immune system. In the **Overall** context, it exhibits particularly high significance scores in professional phagocytes and cytotoxic effector cells. The top expressing cell types are dominated by the myeloid lineage, including multiple monocyte subsets ([CD14-low, CD16-positive monocyte](/details-cell/CL0002396), [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397)), macrophages ([elicited macrophage](/details-cell/CL0000861), [alternatively activated macrophage](/details-cell/CL0000890)), and [myeloid leukocyte](/details-cell/CL0000766) in general. This pattern highlights its fundamental role in initiating responses in the primary cells responsible for pathogen clearance and antigen presentation. Beyond the myeloid compartment, [FCER1G](/details-gene/2207) is a key marker for natural killer (NK) cells, with high CSI scores in both [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939) and [CD16-negative, CD56-bright natural killer cell, human](/details-cell/CL0000938). Its presence is essential for the function of the FcγRIIIa (CD16a) receptor on NK cells, which mediates antibody-dependent cell-mediated cytotoxicity (ADCC), a critical mechanism for eliminating opsonized target cells, such as cancer cells or virally infected cells. The concentrated expression in these specific immune subsets suggests a highly specialized role in immune surveillance and effector functions, rather than a ubiquitous cellular role. ## Pathways and Molecular Function The molecular functions attributed to [FCER1G](/details-gene/2207) are deeply intertwined with immune signaling cascades. Functional annotations confirm its role as a core component of Fc receptor complexes, particularly the '[Fc-epsilon receptor i complex](/details-go/GO:0032998)' and '[Fc-gamma receptor iii complex](/details-go/GO:0033001)', where it is localized to the '[external side of plasma membrane](/details-go/GO:0009897)'. Its primary molecular function involves '[Ige binding](/details-go/GO:0019863)' and '[Igg binding](/details-go/GO:0019864)' as part of these larger receptor structures, enabling signal transduction upon ligand engagement. This structural role translates into its involvement in numerous biological processes. It is central to the '[Fc-epsilon receptor signaling pathway](/details-go/GO:0038095)' and '[Fc-gamma receptor signaling pathway](/details-go/GO:0038094)', which are critical for an '[Innate immune response](/details-go/GO:0045087)'. These pathways drive essential effector functions such as '[Positive regulation of phagocytosis](/details-go/GO:0050766)', '[Neutrophil activation involved in immune response](/details-go/GO:0002283)', and '[Antigen processing and presentation of exogenous peptide antigen via mhc class i](/details-go/GO:0042590)'. Reactome pathway analysis further corroborates this, placing [FCER1G](/details-gene/2207) as a key player in '[Fc epsilon receptor (fceri) signaling](/details-reactome/R-HSA-2454202)' and the broader '[Innate immune system](/details-reactome/R-HSA-168249)'. Its annotated involvement in '[Platelet activation, signaling and aggregation](/details-reactome/R-HSA-76002)' is also consistent with phosphoproteomic studies of human platelets [Link](https://doi.org/10.1021/pr0704130). ## Research Directions Based on its central role as a signaling adaptor in key innate immune cells, research on [FCER1G](/details-gene/2207) can be directed towards understanding its regulatory role in shaping immune outcomes. 1. **Hypothesis 1:** Given the high significance of [FCER1G](/details-gene/2207) in functionally distinct macrophage populations like [elicited macrophage](/details-cell/CL0000861) and [alternatively activated macrophage](/details-cell/CL0000890), it is hypothesized that the stoichiometry of [FCER1G](/details-gene/2207) within different Fc receptor complexes on the macrophage surface is a key determinant of their polarization state (pro-inflammatory vs. anti-inflammatory) upon encountering immune complexes. 2. **Hypothesis 2:** It is hypothesized that [FCER1G](/details-gene/2207) expression level is a rate-limiting factor for antibody-dependent cell-mediated cytotoxicity (ADCC) in [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939), and that modulating its expression could serve as a strategy to enhance the efficacy of therapeutic monoclonal antibodies in oncology. **Key Experimental Approach:** To test the second hypothesis, one could utilize a CRISPR activation (CRISPRa) system to specifically upregulate endogenous [FCER1G](/details-gene/2207) expression in a human NK cell line (e.g., NK-92) engineered to express CD16. The ADCC capacity of these [FCER1G](/details-gene/2207)-high cells against an antibody-coated tumor cell line (e.g., Rituximab-coated Raji cells) would be quantified using a flow cytometry-based killing assay and compared to control NK cells. A significant increase in target cell lysis would support the hypothesis that [FCER1G](/details-gene/2207) is a bottleneck in the ADCC pathway. **Therapeutic Potential:** [FCER1G](/details-gene/2207) represents a compelling, albeit challenging, therapeutic node. As an intracellular signaling molecule, it is not directly targetable by monoclonal antibodies. However, the pathways it regulates are of high clinical interest. **Inhibition** of [FCER1G](/details-gene/2207)-dependent signaling, likely through downstream targets like spleen tyrosine kinase (Syk), is a validated strategy in treating autoimmune and allergic conditions where Fc receptor activation is pathogenic. Conversely, strategies to **enhance** its pathway activity could be beneficial for cancer immunotherapy. This could involve developing novel therapeutic antibodies with engineered Fc domains that promote stronger clustering of FcγRs, leading to amplified downstream signaling through [FCER1G](/details-gene/2207) and more potent ADCC responses.

Genular Protein ID: 1824569880

Symbol: FCERG_HUMAN

Name: High affinity immunoglobulin epsilon receptor subunit gamma

UniProtKB Accession Codes:

P30273 Q5VTW4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CPTAC 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 DrugBank 1 ELM 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 29 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 10 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2138619

Title: Characterization and expression of the gene for the human Fc receptor gamma subunit. Definition of a new gene family.

PubMed ID: 2138619

DOI: 10.1016/s0021-9258(19)39347-0

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 8611682

Title: FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo.

PubMed ID: 8611682

PubMed ID: 18088087

Title: Phosphoproteome of resting human platelets.

PubMed ID: 18088087

DOI: 10.1021/pr0704130

PubMed ID: 18776906

Title: Mincle is an ITAM-coupled activating receptor that senses damaged cells.

PubMed ID: 18776906

DOI: 10.1038/ni.1651

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 26311901

Title: TARM1 is a novel leukocyte receptor complex-encoded ITAM receptor that costimulates proinflammatory cytokine secretion by macrophages and neutrophils.

PubMed ID: 26311901

DOI: 10.4049/jimmunol.1401847

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 28652325

Title: Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules.

PubMed ID: 28652325

DOI: 10.1073/pnas.1706483114

Sequence Information:

  • Length: 86
  • Mass: 9667
  • Checksum: 2F2C7536513D6165
  • Sequence:
    • MIPAVVLLLL LLVEQAAALG EPQLCYILDA ILFLYGIVLT LLYCRLKIQV RKAAITSYEK 
SDGVYTGLST RNQETYETLK HEKPPQ