Details for: TGDS

Gene ID: 23483

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: TGDS

Ensembl ID: ENSG00000088451

Description: TDP-glucose 4,6-dehydratase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 4.18
    rCSI 8.48%
    PRS 86.71
  • melanocyte CL0000148
    CSI 3.89
    rCSI 2.88%
    PRS 95.45
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.68
    rCSI 2.57%
    PRS 98.34
  • hematopoietic stem cell CL0000037
    CSI 3.38
    rCSI 2.25%
    PRS 97.89
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.73
    rCSI 2.78%
    PRS 98.82
  • ciliated epithelial cell CL0000067
    CSI 2.5
    rCSI 2.2%
    PRS 92.36
  • chondrocyte CL0000138
    CSI 2.4
    rCSI 3.82%
    PRS 94.78
  • lung ciliated cell CL1000271
    CSI 2.37
    rCSI 2.74%
    PRS 94.14
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.36
    rCSI 2.94%
    PRS 89.93
  • vascular associated smooth muscle cell CL0000359
    CSI 2.05
    rCSI 6.63%
    PRS 96.77

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):
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    • High
    • Medium
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    • 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 [TGDS](/details-gene/23483) (TDP-glucose 4,6-dehydratase) is a protein-coding gene located on chromosome 13q32.1 that encodes the enzyme dTDP-D-glucose 4,6-dehydratase. This enzyme plays a fundamental role in the [nucleotide-sugar metabolic process](/details-go/GO:0009225), a critical pathway for the synthesis of complex carbohydrates and glycoproteins. While expressed in a wide range of tissues, its significance is particularly high in diverse cell types including [ependymal cell](/details-cell/CL0000065), [melanocyte](/details-cell/CL0000148), and various immune cells such as [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and [hematopoietic stem cell](/details-cell/CL0000037). Clinically, mutations in [TGDS](/details-gene/23483) are known to cause Catel-Manzke syndrome, a rare congenital disorder characterized by skeletal abnormalities, underscoring the gene's essential role in development [Link](https://doi.org/10.1016/j.ajhg.2014.11.004). ## Cellular Roles and Expression Landscape The expression profile of [TGDS](/details-gene/23483) suggests it functions as a critical metabolic enzyme in specific cellular contexts rather than a simple lineage marker. **Overall**, the gene shows the highest significance in a surprisingly diverse set of cell types. It is a top marker in cells of the central nervous system, such as [ependymal cell](/details-cell/CL0000065), and in pigment-producing [melanocyte](/details-cell/CL0000148). Concurrently, it displays high significance in the hematopoietic and immune systems, including in primitive [hematopoietic stem cell](/details-cell/CL0000037), developing [double-positive, alpha-beta thymocyte](/details-cell/CL0000809), and specialized innate immune cells like [plasmacytoid dendritic cell, human](/details-cell/CL0001058). This pattern extends to structural and specialized epithelial cells, with notable significance in [chondrocyte](/details-cell/CL0000138) and [ciliated epithelial cell](/details-cell/CL0000067). This broad but distinct expression landscape is consistent with a fundamental enzymatic function that is particularly vital for the unique metabolic or biosynthetic demands of these specific cell types, such as extracellular matrix production in [chondrocyte](/details-cell/CL0000138) or the synthesis of specific glycoproteins in immune cells. ## Pathways and Molecular Function The primary molecular function of the [TGDS](/details-gene/23483) protein is its enzymatic activity as a dTDP-glucose 4,6-dehydratase, as annotated by its high score for [dTDP-glucose 4,6-dehydratase activity](/details-go/GO:0008460). This function places it centrally within the [nucleotide-sugar metabolic process](/details-go/GO:0009225), where it catalyzes a key step in the biosynthesis of dTDP-L-rhamnose, a precursor for the synthesis of various glycoconjugates and lipopolysaccharides. This core metabolic role likely explains its importance across the varied cell types where it is highly expressed. For instance, the integrity of this pathway is crucial for proper glycosylation of proteins and lipids, which can affect cell adhesion, signaling, and structural integrity, processes essential for skeletal development ([chondrocyte](/details-cell/CL0000138)) and immune cell function ([plasmacytoid dendritic cell, human](/details-cell/CL0001058)). The gene is also annotated with [protein binding](/details-go/GO:0005515), suggesting potential interactions with other metabolic enzymes or regulatory proteins. ## Research Directions The established link between [TGDS](/details-gene/23483) and a developmental syndrome, combined with its specific expression pattern, opens several avenues for future investigation. **Proposed Hypotheses:** 1. The high significance of [TGDS](/details-gene/23483) in [chondrocyte](/details-cell/CL0000138) suggests that its enzymatic activity is a rate-limiting step for synthesizing specific nucleotide sugars required for the glycosylation of key extracellular matrix components like aggrecan. A deficiency in [TGDS](/details-gene/23483) may lead to improperly formed cartilage, directly causing the skeletal abnormalities seen in Catel-Manzke syndrome [Link](https://doi.org/10.1016/j.ajhg.2014.11.004). 2. The elevated significance in [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and [hematopoietic stem cell](/details-cell/CL0000037) indicates a non-skeletal role in immunity. It is hypothesized that [TGDS](/details-gene/23483)-dependent glycosylation is essential for the function or stability of cell surface receptors critical for immune cell trafficking, pathogen recognition, or cytokine signaling in these lineages. **Suggested Experimental Approach:** To test the hypothesis regarding its role in immune function (Hypothesis 2), a targeted approach in a relevant cell model is warranted. One could use CRISPR-Cas9 to knock out [TGDS](/details-gene/23483) in human CD34+ [hematopoietic stem cell](/details-cell/CL0000037). These modified stem cells could then be differentiated *in vitro* towards the [plasmacytoid dendritic cell, human](/details-cell/CL0001058) lineage. The resulting cells would be analyzed by flow cytometry and lectin blotting to assess changes in the glycosylation patterns of key surface markers (e.g., Toll-like receptors). Functional assays, such as measuring Type I interferon production in response to viral ligands (e.g., CpG oligonucleotides), would directly test whether [TGDS](/details-gene/23483) deficiency impairs the primary function of these specialized immune cells. **Therapeutic Potential:** As loss-of-function mutations in [TGDS](/details-gene/23483) cause a severe developmental disorder, it is not a candidate for therapeutic inhibition. Instead, therapeutic strategies would theoretically involve correcting the enzymatic deficiency. For a monogenic disorder like Catel-Manzke syndrome, this could conceptually involve gene replacement therapy to restore functional [TGDS](/details-gene/23483) expression in affected cell types, particularly during early development. However, the systemic nature of the enzyme's role presents significant challenges for delivery and regulation, making such an approach highly speculative at present. It is not considered a conventional drug target for activation or inhibition in other disease contexts based on current data.

Genular Protein ID: 1276752626

Symbol: TGDS_HUMAN

Name: dTDP-D-glucose 4,6-dehydratase

UniProtKB Accession Codes:

O95455 Q05DQ3 Q2TU31 Q5T3Z2 Q9H1T9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 2 EMBL 10 Ensembl 1 GO 2 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 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 Pumba 1 RNAct 1 RefSeq 2 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057823

Title: The DNA sequence and analysis of human chromosome 13.

PubMed ID: 15057823

DOI: 10.1038/nature02379

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: 25480037

Title: Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome.

PubMed ID: 25480037

DOI: 10.1016/j.ajhg.2014.11.004

Sequence Information:

  • Length: 350
  • Mass: 40214
  • Checksum: EE427AD1D91EA43D
  • Sequence:
    • MSAACWEEPW GLPGGFAKRV LVTGGAGFIA SHMIVSLVED YPNYMIINLD KLDYCASLKN 
LETISNKQNY KFIQGDICDS HFVKLLFETE KIDIVLHFAA QTHVDLSFVR AFEFTYVNVY 
GTHVLVSAAH EARVEKFIYV STDEVYGGSL DKEFDESSPK QPTNPYASSK AAAECFVQSY 
WEQYKFPVVI TRSSNVYGPH QYPEKVIPKF ISLLQHNRKC CIHGSGLQTR NFLYATDVVE 
AFLTVLKKGK PGEIYNIGTN FEMSVVQLAK ELIQLIKETN SESEMENWVD YVNDRPTNDM 
RYPMKSEKIH GLGWRPKVPW KEGIKKTIEW YRENFHNWKN VEKALEPFPV