Details for: RNASE6

Gene ID: 6039

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: RNASE6

Ensembl ID: ENSG00000169413

Description: ribonuclease A family member 6

Cell Significance Landscape

Associated with

Significant Cells

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

  • plasmacytoid dendritic cell, human CL0001058
    CSI 27.72
    rCSI 19.36%
    PRS 72.72
  • common dendritic progenitor CL0001029
    CSI 27.48
    rCSI 34.48%
    PRS 79.82
  • myeloid leukocyte CL0000766
    CSI 23.16
    rCSI 21.37%
    PRS 71.53
  • conventional dendritic cell CL0000990
    CSI 22.7
    rCSI 18.95%
    PRS 75.86
  • lung interstitial macrophage CL4033043
    CSI 22.68
    rCSI 50.91%
    PRS 84.84
  • plasmacytoid dendritic cell CL0000784
    CSI 22.49
    rCSI 22.78%
    PRS 89.56
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 19.61
    rCSI 23.68%
    PRS 78.81
  • dendritic cell CL0000451
    CSI 17.24
    rCSI 21.25%
    PRS 78.93
  • colon macrophage CL0009038
    CSI 15.28
    rCSI 70.58%
    PRS 85.86
  • immature B cell CL0000816
    CSI 14.16
    rCSI 10.52%
    PRS 82.38
  • myeloid dendritic cell CL0000782
    CSI 13.4
    rCSI 19.41%
    PRS 84.7
  • promonocyte CL0000559
    CSI 11.9
    rCSI 20.39%
    PRS 77.7
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 11.61
    rCSI 8.94%
    PRS 71.51
  • alveolar macrophage CL0000583
    CSI 8.96
    rCSI 14.75%
    PRS 75.17
  • myeloid dendritic cell, human CL0001057
    CSI 8.46
    rCSI 47.62%
    PRS 88.51
  • mononuclear phagocyte CL0000113
    CSI 7.99
    rCSI 17.58%
    PRS 73.94
  • macrophage CL0000235
    CSI 7.5
    rCSI 13.65%
    PRS 82.26
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 6.86
    rCSI 8.99%
    PRS 82.47
  • lung macrophage CL1001603
    CSI 6.74
    rCSI 15.05%
    PRS 77.77
  • plasmablast CL0000980
    CSI 6.71
    rCSI 5.28%
    PRS 76.35
  • CD14-positive monocyte CL0001054
    CSI 6.24
    rCSI 7.77%
    PRS 80.28
  • inflammatory macrophage CL0000863
    CSI 6.04
    rCSI 10.32%
    PRS 89.26
  • monocyte CL0000576
    CSI 5.59
    rCSI 10.11%
    PRS 79.98
  • small pre-B-II cell CL0000954
    CSI 5.55
    rCSI 5.33%
    PRS 87.93
  • Langerhans cell CL0000453
    CSI 5.42
    rCSI 8.27%
    PRS 83.83
  • intermediate monocyte CL0002393
    CSI 4.19
    rCSI 6.32%
    PRS 74.88
  • Hofbauer cell CL3000001
    CSI 4.18
    rCSI 7.88%
    PRS 79.78
  • unswitched memory B cell CL0000970
    CSI 3.47
    rCSI 2.92%
    PRS 84.96
  • elicited macrophage CL0000861
    CSI 3.43
    rCSI 3.15%
    PRS 78.85
  • IgG plasma cell CL0000985
    CSI 3.25
    rCSI 3.89%
    PRS 84.14
  • early lymphoid progenitor CL0000936
    CSI 2.92
    rCSI 2.57%
    PRS 75.18
  • Kupffer cell CL0000091
    CSI 2.86
    rCSI 6.55%
    PRS 70.46
  • pro-B cell CL0000826
    CSI 2.85
    rCSI 2.36%
    PRS 72.28
  • alternatively activated macrophage CL0000890
    CSI 2.55
    rCSI 3.2%
    PRS 80.87
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.53
    rCSI 6.6%
    PRS 70.16
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.47
    rCSI 2.14%
    PRS 74.52
  • professional antigen presenting cell CL0000145
    CSI 2.47
    rCSI 8.5%
    PRS 86.99
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 1.96
    rCSI 11.87%
    PRS 85.47
  • progenitor cell CL0011026
    CSI 1.95
    rCSI 4.14%
    PRS 66.45
  • mature B cell CL0000785
    CSI 1.72
    rCSI 1.49%
    PRS 80.27
  • innate lymphoid cell CL0001065
    CSI 1.62
    rCSI 3.34%
    PRS 69.35
  • promyelocyte CL0000836
    CSI 1.53
    rCSI 2.2%
    PRS 77.77
  • fraction A pre-pro B cell CL0002045
    CSI 1.37
    rCSI 1.57%
    PRS 84.84
  • dendritic cell, human CL0001056
    CSI 1.3
    rCSI 2%
    PRS 79.06
  • large pre-B-II cell CL0000957
    CSI 0.94
    rCSI 2.68%
    PRS 78.98
  • tissue-resident macrophage CL0000864
    CSI 0.82
    rCSI 3.83%
    PRS 83.75
  • follicular B cell CL0000843
    CSI 0.73
    rCSI 2.66%
    PRS 89.17
  • IgM plasma cell CL0000986
    CSI 0.43
    rCSI 1.95%
    PRS 92.12
  • pre-conventional dendritic cell CL0002010
    CSI 0.25
    rCSI 3.27%
    PRS 91.07

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 [RNASE6](/details-gene/6039) (ribonuclease A family member 6) is a protein-coding gene located on chromosome 14q11.2. It encodes a member of the ribonuclease A superfamily with potent endonuclease activity. Functionally, [RNASE6](/details-gene/6039) is a key component of the innate immune system, where it acts as an antimicrobial peptide involved in the defense response against a range of pathogens, including bacteria and viruses. **Overall**, expression data reveals that [RNASE6](/details-gene/6039) is a highly significant marker for myeloid lineage cells, particularly professional antigen-presenting cells such as [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and [conventional dendritic cell](/details-cell/CL0000990), suggesting a specialized role in first-line host defense. ## Cellular Roles and Expression Landscape The expression profile of [RNASE6](/details-gene/6039) firmly establishes it as a marker and effector molecule within the myeloid compartment of the immune system. **Overall**, it exhibits the highest significance in dendritic cell populations, including [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 27.72) and their progenitors like [common dendritic progenitor](/details-cell/CL0001029) (CSI: 27.48), as well as in [conventional dendritic cell](/details-cell/CL0000990) (CSI: 22.70). This strong and specific expression signature suggests that [RNASE6](/details-gene/6039) is integral to the identity and function of these key antigen-presenting cells. Beyond dendritic cells, [RNASE6](/details--gene/6039) is also highly significant in various macrophage populations, such as [lung interstitial macrophage](/details-cell/CL4033043) and [colon macrophage](/details-cell/CL0009038), as well as other [myeloid leukocyte](/details-cell/CL0000766) subsets. This pattern indicates a broad role in innate immunity across different tissues. The consistent high expression in these cell types, which are specialized for pathogen sensing and clearance, aligns with its known antimicrobial functions. ## Pathways and Molecular Function The function of [RNASE6](/details-gene/6039) is intrinsically linked to its role in host defense, as detailed by its functional annotations. Its involvement in the [Innate immune system](/details-pathway/R-HSA-168249) pathway, specifically as one of the [Antimicrobial peptides](/details-pathway/R-HSA-6803157), is its primary characterized function. This is supported by its association with Gene Ontology terms such as [Antibacterial humoral response](/details-ontology/GO:0019731) and [Defense response to virus](/details-ontology/GO:0051607). Mechanistically, [RNASE6](/details-gene/6039) carries out its function through its [Endonuclease activity](/details-ontology/GO:0004519) and [Rna nuclease activity](/details-ontology/GO:0004540), allowing it to degrade pathogen-derived RNA. Research has demonstrated that it exerts its antimicrobial effects by agglutinating bacterial cells and permeabilizing their membranes ([Link](https://doi.org/10.3390/ijms17040552)). Cellular localization data indicates it operates in the [Extracellular region](/details-ontology/GO:0005576) as a secreted protein and also within the [Lysosome](/details-ontology/GO:0005764), suggesting it can act on pathogens both outside and inside the cell following phagocytosis. This dual localization is consistent with its high expression in phagocytic cells like macrophages and dendritic cells. Its role as an antimicrobial in specific physiological contexts, such as the urinary tract, has been experimentally confirmed ([Link](https://doi.org/10.1038/ki.2014.268)). ## Research Directions Based on its well-defined role as an antimicrobial ribonuclease highly expressed in myeloid cells, several research avenues can be proposed to further elucidate its function and therapeutic potential. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [plasmacytoid dendritic cell, human](/details-cell/CL0001058), which are premier producers of type I interferons in response to viral infections, it is hypothesized that secreted [RNASE6](/details-gene/6039) acts as a primary, direct-acting antiviral effector for these cells, neutralizing viral particles in the extracellular space by degrading their genomic RNA before they can infect nearby cells. 2. Considering its expression in macrophages and its documented localization to the [Lysosome](/details-ontology/GO:0005764), it is hypothesized that intracellular [RNASE6](/details-gene/6039) is essential for the efficient degradation of bacterial RNA within the phagolysosome, a critical step for preventing bacterial escape and for processing pathogen-associated molecular patterns (PAMPs) that trigger downstream immune signaling. **Experimental Approach:** To test the second hypothesis regarding the intracellular role of [RNASE6](/details-gene/6039) in macrophage-mediated pathogen clearance, one could employ a CRISPR-Cas9 knockout strategy in a human monocytic cell line (e.g., THP-1). Following differentiation into macrophages, wild-type and [RNASE6](/details-gene/6039)-knockout cells would be infected with a live, RNA-rich bacterium like *Staphylococcus aureus*. The rate of intracellular bacterial killing would be quantified over time using gentamicin protection assays and colony-forming unit counts. Additionally, RNA-seq analysis of isolated phagolysosomes from both cell types post-infection could directly assess whether the degradation of bacterial RNA is impaired in the absence of [RNASE6](/details-gene/6039). **Therapeutic Potential:** The therapeutic potential of [RNASE6](/details-gene/6039) resides in its application as an antimicrobial agent, suggesting a strategy of **activation or supplementation** rather than inhibition. As a naturally occurring human protein with potent, direct-acting microbicidal activity, recombinant [RNASE6](/details-gene/6039) could be developed as a novel therapeutic for treating infections, particularly those caused by antibiotic-resistant bacteria. Its demonstrated function in the urinary tract ([Link](https://doi.org/10.1038/ki.2014.268)) suggests potential as a locally administered agent for conditions like complicated urinary tract infections. Furthermore, its ability to degrade viral RNA makes it a candidate for development as a broad-spectrum antiviral, potentially delivered via aerosol for respiratory infections.

Genular Protein ID: 1833421720

Symbol: RNAS6_HUMAN

Name: Ribonuclease K6

UniProtKB Accession Codes:

Q93091

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 EMBL 2 Ensembl 1 ExpressionAtlas 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 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 5 PDBsum 5 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 3 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: 8836175

Title: Molecular cloning and characterization of a novel human ribonuclease (RNase k6): increasing diversity in the enlarging ribonuclease gene family.

PubMed ID: 8836175

DOI: 10.1093/nar/24.18.3507

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: 25075772

Title: Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract.

PubMed ID: 25075772

DOI: 10.1038/ki.2014.268

PubMed ID: 27089320

Title: Insights into the antimicrobial mechanism of action of human RNase6: structural determinants for bacterial cell agglutination and membrane permeation.

PubMed ID: 27089320

DOI: 10.3390/ijms17040552

PubMed ID: 27013146

Title: The first crystal structure of human RNase 6 reveals a novel substrate-binding and cleavage site arrangement.

PubMed ID: 27013146

DOI: 10.1042/bcj20160245

Sequence Information:

  • Length: 150
  • Mass: 17196
  • Checksum: 4C1F722066BCC13A
  • Sequence:
    • MVLCFPLLLL LLVLWGPVCP LHAWPKRLTK AHWFEIQHIQ PSPLQCNRAM SGINNYTQHC 
KHQNTFLHDS FQNVAAVCDL LSIVCKNRRH NCHQSSKPVN MTDCRLTSGK YPQCRYSAAA 
QYKFFIVACD PPQKSDPPYK LVPVHLDSIL