Details for: CHST5

Gene ID: 23563

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: CHST5

Ensembl ID: ENSG00000135702

Description: carbohydrate sulfotransferase 5

Cell Significance Landscape

Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 3.41
    rCSI 6.91%
    PRS 99.44
  • small intestine goblet cell CL1000495
    CSI 2.44
    rCSI 5.34%
    PRS 100

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
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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 [CHST5](/details-gene/23563) (Carbohydrate Sulfotransferase 5) encodes a type II transmembrane protein that functions as an N-acetylglucosamine 6-O-sulfotransferase, localizing primarily to the Golgi apparatus. It plays a crucial role in the biosynthesis of keratan sulfate, a key glycosaminoglycan involved in cellular adhesion, signaling, and tissue structure. Expression data indicates that **Overall**, [CHST5](/details-gene/23563) shows highly specific and significant expression in specialized cell types, including [ependymal cell](/details-cell/CL0000065) lining the ventricular system of the brain and [small intestine goblet cell](/details-cell/CL1000495), which is consistent with early research identifying it as highly restricted to intestinal tissue ([Link](https://doi.org/10.1006/bbrc.1999.1324)). Mutations in this gene are known to cause macular corneal dystrophy, highlighting its essential role in maintaining corneal transparency ([Link](https://doi.org/10.1038/79987)). ## Cellular Roles and Expression Landscape The expression profile of [CHST5](/details-gene/23563) points to highly specialized functions in distinct tissues. The **Overall** analysis reveals its most significant expression in [ependymal cell](/details-cell/CL0000065) (CSI: 3.41) and [small intestine goblet cell](/details-cell/CL1000495) (CSI: 2.44). This pattern suggests that [CHST5](/details-gene/23563)-mediated sulfation is critical for the unique functions of these cells. In [small intestine goblet cell](/details-cell/CL1000495), the high significance of [CHST5](/details-gene/23563) is consistent with its role in modifying mucins, which are essential components of the protective mucus layer in the gut. The sulfation of carbohydrate structures on mucins can influence their hydration, viscosity, and interaction with the gut microbiota. In [ependymal cell](/details-cell/CL0000065), which line the cerebral ventricles and regulate cerebrospinal fluid, its high expression may indicate a role in modifying glycoproteins on the cell surface that are involved in cell adhesion, barrier function, or cilia movement. The highly restricted expression pattern suggests that [CHST5](/details-gene/23563) is not a broadly expressed housekeeping gene but rather a specialist enzyme whose activity is required for the specific physiological demands of these cell types. ## Pathways and Molecular Function Functionally, [CHST5](/details-gene/23563) is an enzyme with N-acetylglucosamine 6-o-sulfotransferase activity ([GO:0001517](https://www.ebi.ac.uk/QuickGO/term/GO:0001517)), a specific type of sulfotransferase activity ([GO:0008146](https://www.ebi.ac.uk/QuickGO/term/GO:0008146)). This molecular function is integral to the biological process of keratan sulfate biosynthesis ([GO:0018146](https://www.ebi.ac.uk/QuickGO/term/GO:0018146)) and, more broadly, to the metabolism of glycosaminoglycans ([R-HSA-1630316](https://reactome.org/content/detail/R-HSA-1630316)) and carbohydrates ([GO:0005975](https://www.ebi.ac.uk/QuickGO/term/GO:0005975)). The enzyme carries out its function within the Golgi apparatus ([GO:0005794](https://www.ebi.ac.uk/QuickGO/term/GO:0005794)) and trans-Golgi network ([GO:0005802](https://www.ebi.ac.uk/QuickGO/term/GO:0005802)), where it transfers a sulfo group to the 6-position of N-acetylglucosamine residues on glycoproteins and proteoglycans ([Link](https://doi.org/10.1074/jbc.m304928200)). This activity is a critical step in the elongation and maturation of keratan sulfate chains, as detailed in the Reactome pathway for Keratan sulfate biosynthesis ([R-HSA-2022854](https://reactome.org/content/detail/R-HSA-2022854)). ## Research Directions The specific expression pattern and established molecular function of [CHST5](/details-gene/23563) provide a foundation for investigating its role in health and disease, particularly in tissues where it is highly active. ### Proposed Hypotheses: 1. **Hypothesis:** The high expression of [CHST5](/details-gene/23563) in [small intestine goblet cell](/details-cell/CL1000495) is essential for establishing the structural integrity and protective properties of the colonic mucus barrier. Dysregulation or loss of [CHST5](/details-gene/23563) activity may lead to altered mucin sulfation, compromising barrier function and increasing susceptibility to inflammatory conditions like ulcerative colitis or Crohn's disease. 2. **Hypothesis:** In [ependymal cell](/details-cell/CL0000065), [CHST5](/details-gene/23563) modifies cell-surface proteoglycans to regulate cell-cell adhesion and the proper function of the ependymal cell layer as a barrier between cerebrospinal fluid and brain tissue. A reduction in its activity could impair this barrier, potentially contributing to neuroinflammatory or neurodegenerative processes. ### Experimental Approach: To test the first hypothesis regarding its role in the intestinal barrier, a targeted experimental approach could be employed. A CRISPR-Cas9 knockout of [CHST5](/details-gene/23563) could be generated in human-derived intestinal organoids, which contain a mixed population of intestinal epithelial cells, including goblet cells. The sulfation patterns of secreted mucins (e.g., MUC2) from control versus knockout organoids could be analyzed using lectin blotting or mass spectrometry. Barrier function could be directly assessed using permeability assays (e.g., FITC-dextran flux), and the organoids' response to inflammatory stimuli or bacterial challenge could be measured via cytokine profiling and quantitative PCR for inflammatory markers. ### Therapeutic Potential: Given that loss-of-function mutations in [CHST5](/details-gene/23563) cause macular corneal dystrophy, its therapeutic potential primarily lies in restoration of function for this genetic disorder. Strategies such as gene therapy to deliver a functional copy of the gene to corneal cells could be a viable long-term approach. Conversely, research has shown ectopic expression of a related sulfotransferase in colonic adenocarcinoma ([Link](https://doi.org/10.1093/glycob/12.6.379)), suggesting that altered sulfation patterns contribute to cancer biology. If [CHST5](/details-gene/23563) is found to be aberrantly overexpressed in certain cancers and contributes to pathogenesis (e.g., by modifying cell adhesion or growth factor receptor signaling), it could become a candidate for therapeutic **inhibition** using small molecules or RNAi-based therapies in those specific contexts.

Genular Protein ID: 1924879654

Symbol: CHST5_HUMAN

Name: Carbohydrate sulfotransferase 5

UniProtKB Accession Codes:

Q9GZS9 B2RV23 Q7LCN3 Q9UBY3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 2 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 11 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 MINT 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 2 RNAct 1 Reactome 1 RefSeq 1 SABIO-RK 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10491328

Title: Cloning and characterization of a mammalian N-acetylglucosamine-6-sulfotransferase that is highly restricted to intestinal tissue.

PubMed ID: 10491328

DOI: 10.1006/bbrc.1999.1324

PubMed ID: 11017086

Title: Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene.

PubMed ID: 11017086

DOI: 10.1038/79987

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: 11352640

Title: Sulfation of endothelial mucin by corneal keratan N-acetylglucosamine 6-O-sulfotransferase (GST-4beta).

PubMed ID: 11352640

DOI: 10.1006/bbrc.2001.4668

PubMed ID: 12107080

Title: Ectopic expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma.

PubMed ID: 12107080

DOI: 10.1093/glycob/12.6.379

PubMed ID: 12218059

Title: Enzymatic synthesis in vitro of the disulfated disaccharide unit of corneal keratan sulfate.

PubMed ID: 12218059

DOI: 10.1074/jbc.m207412200

PubMed ID: 12626414

Title: Activities and expression pattern of the carbohydrate sulfotransferase GlcNAc6ST-3 (I-GlcNAc6ST): functional implications.

PubMed ID: 12626414

DOI: 10.1093/glycob/cwg018

PubMed ID: 12855678

Title: Golgi localization of carbohydrate sulfotransferases is a determinant of L-selectin ligand biosynthesis.

PubMed ID: 12855678

DOI: 10.1074/jbc.m304928200

Sequence Information:

  • Length: 411
  • Mass: 46161
  • Checksum: 97642D54BE926E06
  • Sequence:
    • MGMRARVPKV AHSTRRPPAA RMWLPRFSSK TVTVLLLAQT TCLLLFIISR PGPSSPAGGE 
DRVHVLVLSS WRSGSSFLGQ LFSQHPDVFY LMEPAWHVWT TLSQGSAATL HMAVRDLMRS 
IFLCDMDVFD AYMPQSRNLS AFFNWATSRA LCSPPACSAF PRGTISKQDV CKTLCTRQPF 
SLAREACRSY SHVVLKEVRF FNLQVLYPLL SDPALNLRIV HLVRDPRAVL RSREAAGPIL 
ARDNGIVLGT NGKWVEADPH LRLIREVCRS HVRIAEAATL KPPPFLRGRY RLVRFEDLAR 
EPLAEIRALY AFTGLTLTPQ LEAWIHNITH GSGIGKPIEA FHTSSRNARN VSQAWRHALP 
FTKILRVQEV CAGALQLLGY RPVYSADQQR DLTLDLVLPR GPDHFSWASP D