Details for: GCNT3

Gene ID: 9245

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: GCNT3

Ensembl ID: ENSG00000140297

Description: glucosaminyl (N-acetyl) transferase 3, mucin type

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • colon epithelial cell CL0011108
    CSI 18.98
    rCSI 19.89%
    PRS 95.36
  • duct epithelial cell CL0000068
    CSI 11.98
    rCSI 17.52%
    PRS 98.09
  • M cell of gut CL0000682
    CSI 7.46
    rCSI 7.92%
    PRS 96.92
  • lung secretory cell CL1000272
    CSI 7.18
    rCSI 17.76%
    PRS 97.59
  • nasal mucosa goblet cell CL0002480
    CSI 4.2
    rCSI 4.87%
    PRS 96.06
  • goblet cell CL0000160
    CSI 4
    rCSI 3.78%
    PRS 95.23
  • intestine goblet cell CL0019031
    CSI 3.66
    rCSI 3.24%
    PRS 95.2
  • enterocyte of epithelium of large intestine CL0002071
    CSI 3.56
    rCSI 18.7%
    PRS 96.96
  • mucous neck cell CL0000651
    CSI 3.27
    rCSI 4.72%
    PRS 97.25
  • conjunctival epithelial cell CL1000432
    CSI 3.27
    rCSI 5%
    PRS 95.74
  • epithelial cell CL0000066
    CSI 3.01
    rCSI 4.62%
    PRS 88.35
  • squamous epithelial cell CL0000076
    CSI 3
    rCSI 7.13%
    PRS 93.28
  • stem cell CL0000034
    CSI 2.94
    rCSI 2.84%
    PRS 95.11
  • enterocyte CL0000584
    CSI 2.71
    rCSI 4.37%
    PRS 94.12
  • mucus secreting cell CL0000319
    CSI 2.71
    rCSI 4.3%
    PRS 98.29
  • transit amplifying cell of colon CL0009011
    CSI 2.68
    rCSI 3.15%
    PRS 96.98
  • colonocyte CL1000347
    CSI 2.58
    rCSI 3.69%
    PRS 95.23
  • BEST4+ enteroycte CL4030026
    CSI 2.42
    rCSI 3.01%
    PRS 95.88
  • enteroendocrine cell CL0000164
    CSI 2.38
    rCSI 3.25%
    PRS 94.74
  • transit amplifying cell CL0009010
    CSI 2.21
    rCSI 3.38%
    PRS 97.75
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.11
    rCSI 5.69%
    PRS 97.15
  • tracheal goblet cell CL1000329
    CSI 1.73
    rCSI 3.78%
    PRS 97.04
  • colon goblet cell CL0009039
    CSI 1.51
    rCSI 3.58%
    PRS 96.88
  • pancreatic ductal cell CL0002079
    CSI 1.44
    rCSI 2.81%
    PRS 96.73
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.05
    rCSI 2.95%
    PRS 97.37
  • tracheobronchial serous cell CL0019001
    CSI 0.94
    rCSI 4.06%
    PRS 97.39
  • pancreatic PP cell CL0002275
    CSI 0.89
    rCSI 3.52%
    PRS 96.81
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 0.81
    rCSI 4.6%
    PRS 96.34
  • acinar cell of salivary gland CL0002623
    CSI 0.24
    rCSI 5.5%
    PRS 98.29

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 [GCNT3](/details-gene/9245) (glucosaminyl (N-acetyl) transferase 3, mucin type) is a protein-coding gene located on chromosome 15q22.2. It encodes a beta-1,6-N-acetylglucosaminyltransferase, an enzyme that resides in the Golgi apparatus and plays a crucial role in protein post-translational modification. Specifically, it is responsible for the formation of core 2 and core 4 O-glycan branches on mucins ([Link](https://doi.org/10.1074/jbc.274.5.3215), [Link](https://doi.org/10.1074/jbc.274.8.4504)). Its expression profile reflects this function, showing high specificity for various mucus-secreting epithelial cells. The highest significance is observed in [colon epithelial cell](/details-cell/CL0011108)s, highlighting its central role in maintaining the gastrointestinal mucosal barrier. ## Cellular Roles and Expression Landscape The **Overall** expression data identifies [GCNT3](/details-gene/9245) as a key enzyme in mucosal tissues, where it is a defining marker for secretory epithelial lineages. Its significance is exceptionally high in [colon epithelial cell](/details-cell/CL0011108) (CSI: 18.98) and [duct epithelial cell](/details-cell/CL0000068) (CSI: 11.98), suggesting it is a highly active and crucial component of the cellular machinery in these tissues. The gene's role extends across multiple mucosal surfaces, as evidenced by its significant expression in a range of functionally related cell types, including [M cell of gut](/details-cell/CL0000682), [lung secretory cell](/details-cell/CL1000272), [nasal mucosa goblet cell](/details-cell/CL0002480), and [intestine goblet cell](/details-cell/CL0019031). This consistent expression pattern across different anatomical locations underscores its fundamental role in the production and modification of mucins, which are critical for lubrication, protection, and barrier function in these tissues. The presence of [stem cell](/details-cell/CL0000034) among the top expressed cells may indicate a role for [GCNT3](/details-gene/9245) in the differentiation or maintenance of secretory cell lineages. ## Pathways and Molecular Function Functionally, [GCNT3](/details-gene/9245) is an acetylglucosaminyltransferase involved in [O-glycan processing](/details-go/GO:0016266) ([GO:0016266](https://www.ebi.ac.uk/QuickGO/term/GO:0016266)). Its specific molecular function is [beta-1,3-galactosyl-o-glycosyl-glycoprotein beta-1,6-n-acetylglucosaminyltransferase activity](/details-go/GO:0003829) ([GO:0003829](https://www.ebi.ac.uk/QuickGO/term/GO:0003829)), which is integral to the [O-linked glycosylation of mucins](/details-pathway/R-HSA-913709) pathway ([R-HSA-913709](https://reactome.org/content/detail/R-HSA-913709)). These processes occur within the [Golgi membrane](/details-go/GO:0000139) ([GO:0000139](https://www.ebi.ac.uk/QuickGO/term/GO:0000139)) and are essential for the maturation of proteins that are destined for secretion, such as those forming the protective mucus layer. The gene's activity is a key step in building complex carbohydrate structures on proteins, which can influence protein folding, stability, and interaction with other molecules. Its involvement is also noted in broader processes like [intestinal absorption](/details-go/GO:0050892) ([GO:0050892](https://www.ebi.ac.uk/QuickGO/term/GO:0050892)) and [tissue morphogenesis](/details-go/GO:0048729) ([GO:0048729](https://www.ebi.ac.uk/QuickGO/term/GO:0048729)), likely mediated through its role in modifying cell surface and extracellular matrix glycoproteins. ## Research Directions The high and specific expression of [GCNT3](/details-gene/9245) in [colon epithelial cell](/details-cell/CL0011108)s, combined with published evidence, points towards a significant role in intestinal health and disease. Research indicates that [GCNT3](/details-gene/9245) is downregulated in colorectal cancer and its re-expression can inhibit the growth of cancer cells, suggesting it may function as a tumor suppressor ([Link](https://doi.org/10.1038/sj.onc.1209350)). This provides a compelling avenue for further investigation. **Testable Hypotheses:** 1. Loss of [GCNT3](/details-gene/9245) expression during colorectal carcinogenesis leads to aberrant mucin glycosylation, compromising the integrity of the mucosal barrier and facilitating tumor cell invasion and metastasis. 2. In chronic inflammatory airway diseases, pro-inflammatory cytokines such as TNF-alpha ([Link](https://doi.org/10.1007/s10719-005-0292-7)) suppress [GCNT3](/details-gene/9245) activity in [lung secretory cell](/details-cell/CL1000272)s, altering mucus composition and viscosity, which contributes to airway obstruction and pathology. **Proposed Experiment:** To test the first hypothesis, a CRISPR-Cas9 knockout of [GCNT3](/details-gene/9245) could be generated in a colon adenocarcinoma cell line that normally expresses it (e.g., HT-29). The glycomic profile of secreted mucins from knockout and wild-type cells would be compared using lectin blotting and mass spectrometry to confirm altered O-glycosylation patterns. Subsequently, the functional consequences would be assessed using in vitro assays, such as Transwell migration and invasion assays, and in vivo xenograft models to determine if the loss of [GCNT3](/details-gene/9245) promotes a more aggressive cancer phenotype. **Therapeutic Potential:** Given that [GCNT3](/details-gene/9245) appears to function as a tumor suppressor in the colon, its therapeutic potential lies in **activation** or restoration of its function, rather than inhibition. Strategies could involve gene therapy to re-introduce the gene into tumor cells or the development of small-molecule drugs that enhance its expression or enzymatic activity. Such an approach could potentially restore normal mucin production, inhibit cancer cell growth, and re-establish a protective mucosal barrier, making it a novel target for colorectal cancer therapy.

Genular Protein ID: 2129151345

Symbol: GCNT3_HUMAN

Name: Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3

UniProtKB Accession Codes:

O95395

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CTD 1 ChEBI 25 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 5 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 14 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 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 13 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9915862

Title: Molecular cloning and expression of a novel beta-1, 6-N-acetylglucosaminyltransferase that forms core 2, core 4, and I branches.

PubMed ID: 9915862

DOI: 10.1074/jbc.274.5.3215

PubMed ID: 9988682

Title: Control of O-glycan branch formation. Molecular cloning of human cDNA encoding a novel beta1,6-N-acetylglucosaminyltransferase forming core 2 and core 4.

PubMed ID: 9988682

DOI: 10.1074/jbc.274.8.4504

PubMed ID: 17303715

Title: Mucin biosynthesis: identification of the cis-regulatory elements of human C2GnT-M gene.

PubMed ID: 17303715

DOI: 10.1165/rcmb.2006-0334oc

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: 15864435

Title: Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line.

PubMed ID: 15864435

DOI: 10.1007/s10719-005-0292-7

PubMed ID: 16418723

Title: C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells.

PubMed ID: 16418723

DOI: 10.1038/sj.onc.1209350

Sequence Information:

  • Length: 438
  • Mass: 50864
  • Checksum: 1FF0A7B451C88407
  • Sequence:
    • MVQWKRLCQL HYLWALGCYM LLATVALKLS FRLKCDSDHL GLESRESQSQ YCRNILYNFL 
KLPAKRSINC SGVTRGDQEA VLQAILNNLE VKKKREPFTD THYLSLTRDC EHFKAERKFI 
QFPLSKEEVE FPIAYSMVIH EKIENFERLL RAVYAPQNIY CVHVDEKSPE TFKEAVKAII 
SCFPNVFIAS KLVRVVYASW SRVQADLNCM EDLLQSSVPW KYFLNTCGTD FPIKSNAEMV 
QALKMLNGRN SMESEVPPKH KETRWKYHFE VVRDTLHLTN KKKDPPPYNL TMFTGNAYIV 
ASRDFVQHVL KNPKSQQLIE WVKDTYSPDE HLWATLQRAR WMPGSVPNHP KYDISDMTSI 
ARLVKWQGHE GDIDKGAPYA PCSGIHQRAI CVYGAGDLNW MLQNHHLLAN KFDPKVDDNA 
LQCLEEYLRY KAIYGTEL