Details for: RNASE3

Gene ID: 6037

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: RNASE3

Ensembl ID: ENSG00000169397

Description: ribonuclease A family member 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • granulocyte monocyte progenitor cell CL0000557
    CSI 6.54
    rCSI 5.66%
    PRS 99.82
  • promyelocyte CL0000836
    CSI 5.92
    rCSI 8.54%
    PRS 99.63
  • common myeloid progenitor CL0000049
    CSI 5.46
    rCSI 4.41%
    PRS 99.85
  • promonocyte CL0000559
    CSI 3.79
    rCSI 6.5%
    PRS 99.82
  • neutrophil CL0000775
    CSI 3.04
    rCSI 17.02%
    PRS 98.02
  • progenitor cell CL0011026
    CSI 1.99
    rCSI 4.24%
    PRS 99.44
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.69
    rCSI 4.11%
    PRS 98.78
  • myelocyte CL0002193
    CSI 0.93
    rCSI 6.13%
    PRS 99.48

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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  • 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 [RNASE3](/details-gene/6037), also known as Eosinophil Cationic Protein (ECP), is a member of the ribonuclease A superfamily with a crucial role in the innate immune system. It functions as a potent cytotoxic and helminthotoxic protein, primarily through its ribonuclease activity ([Link](https://doi.org/10.1084/jem.170.1.163)). As a key component of the granules of myeloid cells, its expression is most significant in early developmental stages of this lineage, such as [granulocyte monocyte progenitor cells](/details-cell/CL0000557) and [promyelocytes](/details-cell/CL0000836). Upon degranulation, it is released into the extracellular space to combat pathogens, contributing to antimicrobial and inflammatory responses. Its clinical relevance is well-established, with elevated levels serving as a biomarker for various eosinophilic inflammatory diseases ([131398](https://omim.org/entry/131398)). ## Cellular Roles and Expression Landscape The expression profile of [RNASE3](/details-gene/6037) firmly establishes it as a key gene in the myeloid lineage, particularly during granulopoiesis. **Overall**, the gene shows the highest significance in progenitor populations, including [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 6.54), [promyelocyte](/details-cell/CL0000836) (CSI: 5.92), and [common myeloid progenitor](/details-cell/CL0000049) (CSI: 5.46). This pattern suggests that [RNASE3](/details-gene/6037) is not only an effector molecule in mature cells but may also be integral to the developmental program of these lineages. Its continued, albeit lower, significance in mature [neutrophils](/details-cell/CL0000775) (CSI: 3.04) is consistent with its role as a pre-packaged defense protein stored within granules for rapid release. The strong and specific expression within this hematopoietic branch highlights its specialized function in innate immunity. While the dominant signature is myeloid, a minor signal was also observed in [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040), which may suggest a yet-unexplored secondary role in the nervous system or potential cross-reactivity in single-cell datasets. ## Pathways and Molecular Function The functional annotations for [RNASE3](/details-gene/6037) align precisely with its role as a secreted antimicrobial protein. Its molecular functions are centered on [Rna nuclease activity](/details-cell/GO:0004540) and [endonuclease activity](/details-cell/GO:0004519), which form the basis of its cytotoxic effect against pathogens. Furthermore, its ability for [lipopolysaccharide binding](/details-cell/GO:0001530) suggests a mechanism for recognizing and targeting gram-negative bacteria. Biologically, [RNASE3](/details-gene/6037) is a key participant in the [innate immune response](/details-cell/GO:0045087), particularly the [antibacterial humoral response](/details-cell/GO:0019731) and [defense responses to both gram-negative and gram-positive bacteria](/details-cell/GO:0050829). These processes are directly linked to its high expression in myeloid cells. Reactome pathway analysis further situates [RNASE3](/details-gene/6037) within the [antimicrobial peptides](/details-cell/R-HSA-6803157) pathway and, crucially, in [neutrophil degranulation](/details-cell/R-HSA-6798695). This is consistent with its localization to the [azurophil granule lumen](/details-cell/GO:0035578), from where it is released into the [extracellular space](/details-cell/GO:0005615) to exert its defensive functions upon immune activation. ## Research Directions Based on its expression profile and known functions, [RNASE3](/details-gene/6037) presents several avenues for future research. The high significance in progenitor cells, in particular, suggests that its role may extend beyond that of a simple effector molecule. **Testable Hypotheses:** 1. Given its exceptionally high significance in [common myeloid progenitors](/details-cell/CL0000049) and [granulocyte monocyte progenitor cells](/details-cell/CL0000557), [RNASE3](/details-gene/6037) may function as an intrinsic regulator of myeloid lineage commitment. Its ribonuclease activity could be directed at specific host mRNA targets within these progenitor cells to control the translation of key transcription factors, thereby guiding differentiation towards the granulocytic fate. 2. The neurotoxic properties associated with Eosinophil Cationic Protein, coupled with its minor expression signal in a neuronal subtype, suggest that secreted [RNASE3](/details-gene/6037) could play a direct role in neuro-inflammation. During systemic inflammatory conditions, circulating [RNASE3](/details-gene/6037) may compromise the blood-brain barrier and directly impact neuronal health or synaptic function, providing a mechanistic link between peripheral eosinophilic inflammation and neurological symptoms. **Proposed Experimental Approach:** To test the first hypothesis regarding the role of [RNASE3](/details-gene/6037) in myeloid differentiation, one could utilize a CRISPR-Cas9 knockout approach in primary human CD34+ hematopoietic stem and progenitor cells (HSPCs). These engineered HSPCs would be cultured *in vitro* with a cytokine cocktail (e.g., SCF, IL-3, IL-5, G-CSF) to induce differentiation towards the granulocyte lineage. The developmental trajectory of knockout versus wild-type cells could be tracked over time using flow cytometry for lineage-specific surface markers (e.g., CD15, CD16, Siglec-8). Concurrently, performing single-cell RNA sequencing at key timepoints would enable a detailed transcriptomic comparison, revealing any differentiation blocks, delays, or lineage skewing caused by the absence of [RNASE3](/details-gene/6037). **Therapeutic Potential:** [RNASE3](/details-gene/6037) is a validated biomarker for eosinophil-associated diseases, where its high extracellular concentration contributes to tissue damage. This makes it an attractive therapeutic target for **inhibition**. Because it is a secreted, extracellular protein, it is highly accessible to biologic drugs. A therapeutic strategy could involve the development of a neutralizing monoclonal antibody that specifically binds and inhibits the ribonucleolytic active site of [RNASE3](/details-gene/6037). Such an agent could be employed to reduce the cytotoxic side effects of eosinophil degranulation in conditions like severe asthma, hypereosinophilic syndrome, or eosinophilic esophagitis, thereby dampening inflammation without requiring broad immunosuppression.

Genular Protein ID: 739921932

Symbol: ECP_HUMAN

Name: Eosinophil cationic protein

UniProtKB Accession Codes:

P12724 Q4VBC1 Q8WTP7 Q8WZ62 Q9GZN9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EC 1 EMBL 19 Ensembl 1 EvolutionaryTrace 1 GO 16 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 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 11 PDBsum 11 PIR 1 PRIDE 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2473157

Title: Human eosinophil cationic protein. Molecular cloning of a cytotoxin and helminthotoxin with ribonuclease activity.

PubMed ID: 2473157

DOI: 10.1084/jem.170.1.163

PubMed ID: 2387583

Title: Structure and chromosome localization of the human eosinophil-derived neurotoxin and eosinophil cationic protein genes: evidence for intronless coding sequences in the ribonuclease gene superfamily.

PubMed ID: 2387583

DOI: 10.1016/0888-7543(90)90197-3

PubMed ID: 2745977

Title: Eosinophil cationic protein cDNA. Comparison with other toxic cationic proteins and ribonucleases.

PubMed ID: 2745977

PubMed ID: 11102386

Title: Sequence variation at two eosinophil-associated ribonuclease loci in humans.

PubMed ID: 11102386

DOI: 10.1093/genetics/156.4.1949

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 3458170

Title: Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease.

PubMed ID: 3458170

DOI: 10.1073/pnas.83.10.3146

PubMed ID: 2501794

Title: Antibiotic proteins of human polymorphonuclear leukocytes.

PubMed ID: 2501794

DOI: 10.1073/pnas.86.14.5610

PubMed ID: 18694936

Title: Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase.

PubMed ID: 18694936

DOI: 10.1074/jbc.m801196200

PubMed ID: 19450231

Title: Bactericidal and membrane disruption activities of the eosinophil cationic protein are largely retained in an N-terminal fragment.

PubMed ID: 19450231

DOI: 10.1042/bj20082330

PubMed ID: 20690710

Title: Eosinophil cationic protein aggregation: identification of an N-terminus amyloid prone region.

PubMed ID: 20690710

DOI: 10.1021/bm100334u

PubMed ID: 25944712

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

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 10606511

Title: Crystal structure of eosinophil cationic protein at 2.4 A resolution.

PubMed ID: 10606511

DOI: 10.1021/bi9919145

PubMed ID: 10903870

Title: Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 A resolution.

PubMed ID: 10903870

DOI: 10.1006/jmbi.2000.3939

PubMed ID: 12356310

Title: The crystal structure of eosinophil cationic protein in complex with 2',5'-ADP at 2.0 A resolution reveals the details of the ribonucleolytic active site.

PubMed ID: 12356310

DOI: 10.1021/bi0264521

Sequence Information:

  • Length: 160
  • Mass: 18385
  • Checksum: D7BED24F67B23FA9
  • Sequence:
    • MVPKLFTSQI CLLLLLGLMG VEGSLHARPP QFTRAQWFAI QHISLNPPRC TIAMRAINNY 
RWRCKNQNTF LRTTFANVVN VCGNQSIRCP HNRTLNNCHR SRFRVPLLHC DLINPGAQNI 
SNCTYADRPG RRFYVVACDN RDPRDSPRYP VVPVHLDTTI