Details for: RFNG

Gene ID: 5986

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: RFNG

Ensembl ID: ENSG00000169733

Description: RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • skin fibroblast CL0002620
    CSI 5.93
    rCSI 5.11%
    PRS 86.36
  • mature astrocyte CL0002627
    CSI 4.06
    rCSI 17.25%
    PRS 80.16
  • suprabasal keratinocyte CL4033013
    CSI 3.61
    rCSI 5.89%
    PRS 55.38
  • duct epithelial cell CL0000068
    CSI 3.45
    rCSI 5.05%
    PRS 90.64
  • epithelial cell of lung CL0000082
    CSI 3.43
    rCSI 2.85%
    PRS 87.78
  • multi-ciliated epithelial cell CL0005012
    CSI 2.94
    rCSI 2.93%
    PRS 81.02
  • bronchus fibroblast of lung CL2000093
    CSI 2.71
    rCSI 2.2%
    PRS 86.21
  • precursor B cell CL0000817
    CSI 2.66
    rCSI 2.33%
    PRS 91.71
  • neural crest cell CL0011012
    CSI 2.64
    rCSI 2.09%
    PRS 77.9
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.62
    rCSI 3.13%
    PRS 71.55
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.49
    rCSI 2.25%
    PRS 85.37
  • ionocyte CL0005006
    CSI 2.45
    rCSI 2.62%
    PRS 88.66
  • promyelocyte CL0000836
    CSI 2.43
    rCSI 3.51%
    PRS 90.28
  • stem cell CL0000034
    CSI 2.34
    rCSI 2.25%
    PRS 81.78
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.28
    rCSI 2.94%
    PRS 72.58
  • perivascular cell CL4033054
    CSI 2.24
    rCSI 3.06%
    PRS 90.4
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.12
    rCSI 2.64%
    PRS 69.27
  • ciliated epithelial cell CL0000067
    CSI 2.04
    rCSI 1.8%
    PRS 77.33
  • extravillous trophoblast CL0008036
    CSI 2
    rCSI 2.47%
    PRS 85.1
  • vascular associated smooth muscle cell CL0000359
    CSI 1.89
    rCSI 6.14%
    PRS 84.67
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.84
    rCSI 3.26%
    PRS 70.9
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.78
    rCSI 1.71%
    PRS 85.84
  • chondrocyte CL0000138
    CSI 1.76
    rCSI 2.8%
    PRS 81.13
  • pancreatic acinar cell CL0002064
    CSI 1.73
    rCSI 2.3%
    PRS 90.76
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.72
    rCSI 2.76%
    PRS 72.68
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.71
    rCSI 5.05%
    PRS 87.25
  • placental villous trophoblast CL2000060
    CSI 1.68
    rCSI 2.6%
    PRS 85.41
  • basal cell of epidermis CL0002187
    CSI 1.6
    rCSI 2.83%
    PRS 56.65
  • hepatocyte CL0000182
    CSI 1.59
    rCSI 2.84%
    PRS 85.89
  • retinal cone cell CL0000573
    CSI 1.52
    rCSI 2.45%
    PRS 78.08
  • peripheral nervous system neuron CL2000032
    CSI 1.46
    rCSI 1.99%
    PRS 79.5
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.3
    rCSI 3.31%
    PRS 78.91
  • alveolar macrophage CL0000583
    CSI 1.29
    rCSI 2.12%
    PRS 89.37
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.27
    rCSI 2.84%
    PRS 72.17
  • mesenchymal cell CL0008019
    CSI 1.2
    rCSI 3.04%
    PRS 80.8
  • melanocyte of skin CL1000458
    CSI 0.96
    rCSI 1.31%
    PRS 55.52
  • podocyte CL0000653
    CSI 0.87
    rCSI 3.87%
    PRS 87.24
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.83
    rCSI 2.03%
    PRS 69.21
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.82
    rCSI 4.82%
    PRS 71.82
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.8
    rCSI 2.31%
    PRS 85.98
  • glial cell CL0000125
    CSI 0.69
    rCSI 2.63%
    PRS 79.05
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.67
    rCSI 2.54%
    PRS 71.7
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.67
    rCSI 2.08%
    PRS 72.77
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.53
    rCSI 1.9%
    PRS 69.39

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 [RFNG](/details-gene/5986), or RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, is a key enzyme that functions as a modulator of the highly conserved Notch signaling pathway. Localized to the Golgi apparatus, it modifies Notch receptors by catalyzing the addition of N-acetylglucosamine to O-linked fucose residues, an action that potentiates receptor activation. This function places [RFNG](/details-gene/5986) at the center of critical cellular processes, including cell fate determination, differentiation, and tissue patterning during development. Its expression profile is widespread, with particularly high significance in structural and developmental cell types such as [skin fibroblast](/details-cell/CL0002620), [mature astrocyte](/details-cell/CL0002627), and various epithelial cells, underscoring its fundamental role in organogenesis and tissue maintenance. Dysregulation of [RFNG](/details-gene/5986) is implicated in developmental abnormalities and disease, as suggested by its clinical association ([602578](https://omim.org/entry/602578)). ## Cellular Roles and Expression Landscape The expression landscape of [RFNG](/details-gene/5986) highlights its integral role in establishing and maintaining tissue architecture and mediating developmental processes. **Overall**, the gene shows the highest significance in cells responsible for structural support and boundary formation. This is led by [skin fibroblast](/details-cell/CL0002620) (CSI: 5.93) and various epithelial populations, including [suprabasal keratinocyte](/details-cell/CL4033013), [duct epithelial cell](/details-cell/CL0000068), and [epithelial cell of lung](/details-cell/CL0000082). This pattern suggests a crucial function in skin integrity, organ lining, and connective tissue homeostasis. Furthermore, [RFNG](/details-gene/5986) is highly significant in the nervous system, with prominent expression in [mature astrocyte](/details-cell/CL0002627) (CSI: 4.06) and specific neuronal subtypes like [VIP GABAergic cortical interneuron](/details-cell/CL4023016). This is consistent with the known role of Notch signaling in both neurodevelopment and the maintenance of the adult central nervous system. The gene's importance in cell differentiation is further supported by its expression in various progenitor cells, including [precursor B cell](/details-cell/CL0000817), [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), and [neural crest cell](/details-cell/CL0011012), indicating its involvement in directing cell fate decisions across multiple lineages. ## Pathways and Molecular Function The primary molecular function of [RFNG](/details-gene/5986) is its O-fucosylpeptide 3-beta-n-acetylglucosaminyltransferase activity ([GO:0033829](https://www.ebi.ac.uk/QuickGO/term/GO:0033829)), which is executed within the [Golgi membrane](/details-cell/GO0000139) ([Link](https://doi.org/10.1242/dev.124.11.2245)). This enzymatic activity is a critical step in the post-translational modification of Notch receptors. Specifically, [RFNG](/details-gene/5986) is a central player in the [Signaling by notch](/details-cell/R-HSA-157118) pathway, particularly during [Pre-notch processing in golgi](/details-cell/R-HSA-1912420). By glycosylating Notch, [RFNG](/details-gene/5986) acts as a [Positive regulation of notch signaling pathway](/details-cell/GO0045747) component, enhancing the sensitivity of the receptor to certain ligands like Delta while inhibiting sensitivity to others like Jagged. This differential modulation allows [RFNG](/details-gene/5986) to fine-tune cellular responses to environmental cues, which is essential for processes like [Pattern specification process](/details-cell/GO0007389) during embryogenesis. This function directly connects its molecular activity to its observed role in broad biological processes such as [Animal organ morphogenesis](/details-cell/GO0009887) and [Nervous system development](/details-cell/GO0007399). ## Research Directions Given that [RFNG](/details-gene/5986) is a key modulator of Notch signaling, a pathway frequently dysregulated in disease, its cell-specific roles present several avenues for future research. **Proposed Hypotheses:** 1. Based on its high significance in [skin fibroblast](/details-cell/CL0002620) and [suprabasal keratinocyte](/details-cell/CL4033013), [RFNG](/details-gene/5986) may be a critical regulator of skin homeostasis and wound healing by controlling the balance between proliferation and differentiation in response to injury. 2. The prominent expression of [RFNG](/details-gene/5986) in diverse progenitor cells, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and [precursor B cell](/details-cell/CL0000817), suggests that its activity is essential for proper lineage commitment during hematopoiesis, and its misexpression could contribute to hematological disorders. 3. In cancers derived from tissues where [RFNG](/details-gene/5986) is highly expressed, such as the lung ([epithelial cell of lung](/details-cell/CL0000082)), its overexpression could potentiate oncogenic Notch signaling, thereby promoting tumor growth and resistance to therapy. **Experimental Approach:** To test the hypothesis regarding its role in skin regeneration (Hypothesis 1), a compelling experiment would involve a conditional knockout mouse model. Using a KRT14-Cre driver to specifically delete [RFNG](/details-gene/5986) in keratinocytes, researchers could perform full-thickness excisional wound assays. The rate of wound closure, degree of re-epithelialization, and cellular composition of the healing tissue could be compared between knockout and wild-type mice. Subsequent molecular analysis using single-cell RNA-sequencing of the wound bed would reveal how the loss of [RFNG](/details-gene/5986) alters the transcriptional trajectories of keratinocytes and fibroblasts during the healing process. **Therapeutic Potential:** As a positive regulator of the often-oncogenic Notch pathway, [RFNG](/details-gene/5986) represents a potential target for therapeutic **inhibition**. In cancers that exhibit Notch pathway dependency, such as certain types of lung cancer or T-cell acute lymphoblastic leukemia, targeting the enzymatic activity of [RFNG](/details-gene/5986) with a small molecule inhibitor could offer a strategy to suppress tumor growth. However, its widespread expression in healthy tissues implies that systemic inhibition could lead to significant on-target toxicities. Therefore, the development of tumor-targeted delivery systems or inhibitors that exploit cancer-specific metabolic states would be crucial for translating this concept into a viable therapy.

Genular Protein ID: 3840196290

Symbol: RFNG_HUMAN

Name: O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase

UniProtKB Accession Codes:

Q9Y644 O00588

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CTD 1 ChEBI 13 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 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 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 6 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 10341080

Title: Genomic structure, mapping, and expression analysis of the mammalian Lunatic, Manic, and Radical fringe genes.

PubMed ID: 10341080

DOI: 10.1007/s003359901039

PubMed ID: 9187150

Title: A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway.

PubMed ID: 9187150

DOI: 10.1242/dev.124.11.2245

Sequence Information:

  • Length: 331
  • Mass: 36424
  • Checksum: 986270FFA7C13573
  • Sequence:
    • MSRARGALCR ACLALAAALA ALLLLPLPLP RAPAPARTPA PAPRAPPSRP AAPSLRPDDV 
FIAVKTTRKN HGPRLRLLLR TWISRARQQT FIFTDGDDPE LELQGGDRVI NTNCSAVRTR 
QALCCKMSVE YDKFIESGRK WFCHVDDDNY VNARSLLHLL SSFSPSQDVY LGRPSLDHPI 
EATERVQGGR TVTTVKFWFA TGGAGFCLSR GLALKMSPWA SLGSFMSTAE QVRLPDDCTV 
GYIVEGLLGA RLLHSPLFHS HLENLQRLPP DTLLQQVTLS HGGPENPHNV VNVAGGFSLH 
QDPTRFKSIH CLLYPDTDWC PRQKQGAPTS R

Genular Protein ID: 3739245859

Symbol: Q8N9R1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8N9R1

Database IDs:

ARBA 11 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 11 DNASU 1 DisGeNET 1 EC 2 EMBL 2 GO 3 Gene3D 1 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 Rhea 6 SAM 1 SMR 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 197
  • Mass: 20903
  • Checksum: C548D161D0D7143B
  • Sequence:
    • MSVEYDKFIE SGRKWFCHVD DDNYVNARSL LHLLSSFSPS QDVYLGRPSL DHPIEATERV 
QGGRTVSVGA DAIGADAFLD TSPGGTAEGV ESWLEKGIGL GAQADPPRWF ACGVSGAGQE 
ALTVLGREGV SGPGGEGLEA TGQWPAEAPG SFCSKKLLLP GWDLLRGSLR KMPGESHEES 
GVRSPVLGSS DHHPIFR

Genular Protein ID: 4070615169

Symbol: F5H3H7_HUMAN

Name: N/A

UniProtKB Accession Codes:

F5H3H7

Database IDs:

ARBA 11 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChEBI 11 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 2 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 Rhea 6 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 205
  • Mass: 22804
  • Checksum: FFB1B9D30AB704D9
  • Sequence:
    • MSVEYDKFIE SGRKWFCHVD DDNYVNARSL LHLLSSFSPS QDVYLGRPSL DHPIEATERV 
QGGRTVTTVK FWFATGGAGF CLSRGLALKM SPWASLGSFM STAEQVRLPD DCTVGYIVEG 
LLGARLLHSP LFHSHLENLQ RLPPDTLLQQ VTLSHGGPEN PHNVVNVAGG FSLHQDPTRF 
KSIHCLLYPD TDWCPRQKQG APTSR