Details for: FCRL2

Gene ID: 79368

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: FCRL2

Ensembl ID: ENSG00000132704

Description: Fc receptor like 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • transitional stage B cell CL0000818
    CSI 10.18
    rCSI 33.32%
    PRS 99.02
  • mature B cell CL0000785
    CSI 9.04
    rCSI 7.86%
    PRS 98.74
  • IgG plasma cell CL0000985
    CSI 8.41
    rCSI 10.07%
    PRS 97.16
  • unswitched memory B cell CL0000970
    CSI 5.18
    rCSI 4.36%
    PRS 98.97
  • IgA plasma cell CL0000987
    CSI 4.63
    rCSI 4.74%
    PRS 95.45
  • immature B cell CL0000816
    CSI 4.59
    rCSI 3.41%
    PRS 98.59
  • class switched memory B cell CL0000972
    CSI 4.56
    rCSI 3.41%
    PRS 98.57
  • naive B cell CL0000788
    CSI 3.59
    rCSI 3.08%
    PRS 97.84
  • plasmablast CL0000980
    CSI 2.86
    rCSI 2.25%
    PRS 96.83
  • intestinal tuft cell CL0019032
    CSI 1.81
    rCSI 2.77%
    PRS 96.33
  • germinal center B cell CL0000844
    CSI 0.99
    rCSI 2.94%
    PRS 97.95

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 [FCRL2](/details-gene/79368) (Fc Receptor Like 2) is a protein-coding gene located on chromosome 1q23.1. It encodes a type I transmembrane glycoprotein belonging to the immunoglobulin receptor superfamily. As its name suggests, it is structurally related to classical Fc receptors but its function is distinct. Initial characterization studies identified [FCRL2](/details-gene/79368) as part of a family of Fc receptor homologs, also known as Immunoglobulin-like Receptors (IRTA), with highly specific expression in B-lymphocytes ([Link](https://doi.org/10.1073/pnas.171308498), [Link](https://doi.org/10.1182/blood.v99.8.2662)). Functional annotations suggest it acts as a cell surface signaling receptor, likely involved in modulating immune responses through its interaction with intracellular signaling molecules such as protein phosphatases. ## Cellular Roles and Expression Landscape The expression profile of [FCRL2](/details-gene/79368) underscores its role as a key marker for the B cell lineage. **Overall**, the gene shows its highest significance across various stages of B cell development and differentiation. It is a particularly strong marker for `[transitional stage B cell](/details-cell/CL0000818)` (CSI: 10.18) and `[mature B cell](/details-cell/CL0000785)` (CSI: 9.04), suggesting a role from early maturation onwards. This high expression is maintained in terminally differentiated and memory B cell populations, including: * `[IgG plasma cell](/details-cell/CL0000985)` (CSI: 8.41) * `[unswitched memory B cell](/details-cell/CL0000970)` (CSI: 5.18) * `[IgA plasma cell](/details-cell/CL0000987)` (CSI: 4.63) * `[class switched memory B cell](/details-cell/CL0000972)` (CSI: 4.56) The broad and significant expression across naive, memory, and plasma cell subsets indicates that [FCRL2](/details-gene/79368) is likely involved in regulating B cell function throughout the humoral immune response. Its consistent presence suggests it is more than just a developmental marker and may have continuous signaling functions. Notably, a significant, albeit lower, expression is also observed in `[intestinal tuft cell](/details-cell/CL0019032)` (CSI: 1.81), hinting at a potential role in mucosal immunity outside the canonical B cell compartment. ## Pathways and Molecular Function Functionally, [FCRL2](/details-gene/79368) operates as a transmembrane signaling receptor on the [external side of plasma membrane](/details-cell/GO:0009897). Its involvement in the [cell surface receptor signaling pathway](/details-cell/GO:0007166) is central to its function within the [immune response](/details-cell/GO:0006955). The protein's molecular activities include [protein binding](/details-cell/GO:0005515) and specifically [protein phosphatase binding](/details-cell/GO:0019903), which is consistent with early studies identifying it as a potential inhibitory receptor ([Link](https://doi.org/10.1006/bbrc.2000.4213)). This suggests that upon ligand binding, [FCRL2](/details-gene/79368) may recruit phosphatases to the plasma membrane to dephosphorylate key signaling intermediates, thereby dampening B cell activation signals. This role as a [signaling adaptor](/details-cell/GO:0035591) positions [FCRL2](/details-gene/79368) as a potential regulator of B cell receptor (BCR) signaling thresholds and cellular activation. ## Research Directions The specific and sustained expression of [FCRL2](/details-gene/79368) across the B cell lineage, combined with its putative inhibitory function, opens several avenues for future research. One study has noted its expression in B-chronic lymphocytic leukemia, highlighting its clinical relevance ([Link](https://doi.org/10.1093/intimm/dxl069)). **Proposed Hypotheses:** 1. Given its high expression on `[transitional stage B cell](/details-cell/CL0000818)`, [FCRL2](/details-gene/79368) functions as a critical regulator of central B cell tolerance by modulating BCR signal strength during negative selection checkpoints in the bone marrow. 2. The sustained high expression on memory B cells and plasma cells suggests [FCRL2](/details-gene/79368) is involved in the long-term maintenance and survival of these populations, or in regulating the magnitude of secondary antibody responses. 3. The presence of [FCRL2](/details-gene/79368) on `[intestinal tuft cell](/details-cell/CL0019032)` indicates a novel role in mucosal immunity, where it may sense luminal antigens or microbial products to initiate type 2 immune responses by communicating with neighboring immune cells. **Key Experimental Approach:** To test the hypothesis that [FCRL2](/details-gene/79368) regulates B cell tolerance (Hypothesis 1), a B cell-specific conditional knockout mouse model (`FCRL2` fl/fl x CD19-Cre) could be generated. The developmental progression of B cells in the bone marrow and spleen of these mice could be analyzed by flow cytometry. A key prediction is that `FCRL2`-deficient mice may exhibit a leaky central tolerance checkpoint, leading to an increased number of autoreactive B cells in the periphery. Furthermore, B cells isolated from these mice could be stimulated *in vitro* through their BCR to directly measure downstream signaling events (e.g., phosphorylation of Syk, BLNK, and PLCγ2) using phosphoflow cytometry or Western blotting, to determine if `FCRL2` deficiency leads to hyper-responsiveness. **Therapeutic Potential:** The high and restricted expression of [FCRL2](/details-gene/79368) on the surface of B cells, including malignant B cells, makes it an excellent candidate for targeted therapies. As a cell surface protein, it is readily accessible to antibody-based therapeutics. Therefore, [FCRL2](/details-gene/79368) represents a promising target for the development of antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), or CAR-T cell therapies aimed at depleting B cells in the context of B-cell malignancies or autoimmune diseases. The therapeutic strategy would be B cell ablation via targeted inhibition or cytotoxicity.

Genular Protein ID: 3092767506

Symbol: FCRL2_HUMAN

Name: Fc receptor-like protein 2

UniProtKB Accession Codes:

Q96LA5 A0N0M5 A1L307 A6NMS0 Q6NTA1 Q9BZI4 Q9BZI5 Q9BZI6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 3 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 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 4 RNAct 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11493702

Title: Identification of a family of Fc receptor homologs with preferential B cell expression.

PubMed ID: 11493702

DOI: 10.1073/pnas.171308498

PubMed ID: 11162587

Title: Molecular cloning and characterization of SPAP1, an inhibitory receptor.

PubMed ID: 11162587

DOI: 10.1006/bbrc.2000.4213

PubMed ID: 11929751

Title: IRTAs: a new family of immunoglobulin-like receptors differentially expressed in B cells.

PubMed ID: 11929751

DOI: 10.1182/blood.v99.8.2662

PubMed ID: 12037601

Title: A family of highly diverse human and mouse genes structurally links leukocyte FcR, gp42 and PECAM-1.

PubMed ID: 12037601

DOI: 10.1007/s00251-002-0436-x

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 16710414

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

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 16849395

Title: Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia.

PubMed ID: 16849395

DOI: 10.1093/intimm/dxl069

Sequence Information:

  • Length: 508
  • Mass: 55542
  • Checksum: 9AB30E0411B41EDC
  • Sequence:
    • MLLWSLLVIF DAVTEQADSL TLVAPSSVFE GDSIVLKCQG EQNWKIQKMA YHKDNKELSV 
FKKFSDFLIQ SAVLSDSGNY FCSTKGQLFL WDKTSNIVKI KVQELFQRPV LTASSFQPIE 
GGPVSLKCET RLSPQRLDVQ LQFCFFRENQ VLGSGWSSSP ELQISAVWSE DTGSYWCKAE 
TVTHRIRKQS LQSQIHVQRI PISNVSLEIR APGGQVTEGQ KLILLCSVAG GTGNVTFSWY 
REATGTSMGK KTQRSLSAEL EIPAVKESDA GKYYCRADNG HVPIQSKVVN IPVRIPVSRP 
VLTLRSPGAQ AAVGDLLELH CEALRGSPPI LYQFYHEDVT LGNSSAPSGG GASFNLSLTA 
EHSGNYSCEA NNGLGAQCSE AVPVSISGPD GYRRDLMTAG VLWGLFGVLG FTGVALLLYA 
LFHKISGESS ATNEPRGASR PNPQEFTYSS PTPDMEELQP VYVNVGSVDV DVVYSQVWSM 
QQPESSANIR TLLENKDSQV IYSSVKKS

Genular Protein ID: 3778085746

Symbol: B4E0W2_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4E0W2

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Gene3D 1 InterPro 6 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 SAM 1 SMART 2 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 202
  • Mass: 22997
  • Checksum: FFF51E3369F52257
  • Sequence:
    • MLLWSLLVIF DAVTEQADSL TLVAPSSVFE GDSIVLKCQG EQNWKIQKMA YHKDNKELSV 
FKKFSDFLIQ SAVLSDSGNY FCSTKGQLFL WDKTSNIVKI KVQELFQRPV LTASSFQPIE 
GGPVSLKCET RLSPQRLDVQ LQFCFFRENQ VLGSGWSSSP ELQISAVWSE DTGSYWCKAE 
TVTHRIRKQS LQSQIHVQSK YQ

Genular Protein ID: 468880103

Symbol: B4DVJ9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DVJ9

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 1 InterPro 6 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 2 ProteomicsDB 1 RefSeq 1 SAM 2 SMART 2 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 444
  • Mass: 48349
  • Checksum: 8573D30AE66B5C64
  • Sequence:
    • MLLWSLLVIF DAVTEQADSL TLVAPSSVFE GDSIVLKCQG EQNWKIQKMA YHKDNKELSV 
FKKFSDFLIQ SAVLSDSGNY FCSTKGQLFL WDKTSNIVKI KVQELFQRPV LTASSFQPIE 
GGPVSLKCET RLSPQRLDVQ LQFCFFRENQ VLGSGWSSSP ELQISAVWSE DTGSYWCKAE 
TVTHRIRKQS LQSQIHVQRI PISNVSLEIR APGGQVTEGQ KLILLCSVAG GTGNVTFSWY 
REATGTSMGK KTQRSLSAEL EIPAVKESDA GKYYCRADNG HVPIQSKVVN IPVRIPVSRP 
VLTLRSPGAQ AAVGDLLELH CEALRGSPPI LYQFYHEDVT LGNSSAPSGG GASFNLSLTA 
EHSGNYSCEA NNGLGAQCSE AVPVSISGPD GYRRDLMTAG VLWGLFGVLG FTGVALLLYA 
LFHKISGESS ATNEPRTPKS STLL