Details for: SLC35C1

Gene ID: 55343

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: SLC35C1

Ensembl ID: ENSG00000181830

Description: solute carrier family 35 member C1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 3.88
    rCSI 9.1%
    PRS 94.56
  • secretory cell CL0000151
    CSI 3.45
    rCSI 3.6%
    PRS 96.49
  • nasal mucosa goblet cell CL0002480
    CSI 3.15
    rCSI 3.65%
    PRS 96.31
  • hepatocyte CL0000182
    CSI 3.03
    rCSI 5.43%
    PRS 95.43
  • intestine goblet cell CL0019031
    CSI 2.88
    rCSI 2.55%
    PRS 95.72
  • goblet cell CL0000160
    CSI 2.83
    rCSI 2.67%
    PRS 95.68
  • foveolar cell of stomach CL0002179
    CSI 2.76
    rCSI 5.88%
    PRS 97.24
  • conjunctival epithelial cell CL1000432
    CSI 2.69
    rCSI 4.11%
    PRS 96.24
  • colon epithelial cell CL0011108
    CSI 2.67
    rCSI 2.8%
    PRS 95.83
  • stem cell CL0000034
    CSI 2.46
    rCSI 2.37%
    PRS 95.66
  • colonocyte CL1000347
    CSI 2.41
    rCSI 3.45%
    PRS 95.67
  • tracheal goblet cell CL1000329
    CSI 2.24
    rCSI 4.89%
    PRS 97.28
  • club cell CL0000158
    CSI 1.78
    rCSI 2.6%
    PRS 95.43
  • colon goblet cell CL0009039
    CSI 1.29
    rCSI 3.07%
    PRS 97.16

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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    • 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 [SLC35C1](/details-gene/55343) encodes the Solute Carrier Family 35 Member C1, a Golgi-localized antiporter responsible for transporting GDP-fucose from the cytoplasm into the Golgi lumen. This function is critical for the fucosylation of proteins and lipids, a key post-translational modification involved in numerous cellular processes. Expression data indicates that **Overall**, [SLC35C1](/details-gene/55343) is most significant in cell types with high secretory and metabolic activity, such as [hepatocytes](/details-cell/CL0000182) and various types of [goblet cells](/details-cell/CL0000160). Clinically, mutations in [SLC35C1](/details-gene/55343) lead to Congenital Disorder of Glycosylation Type IIc (CDG-IIc), also known as Leukocyte Adhesion Deficiency Type II (LAD-II) ([266265](https://omim.org/entry/266265)), a rare genetic disorder characterized by severe developmental and immunological defects [Link](https://doi.org/10.1038/ng0501-69), [Link](https://doi.org/10.1038/ng0501-73). ## Cellular Roles and Expression Landscape The expression profile of [SLC35C1](/details-gene/55343) highlights its essential role in specialized secretory and metabolic cells. **Overall**, the gene shows the highest significance in [midzonal region hepatocyte](/details-cell/CL0019028) (CSI: 3.88) and generic [secretory cell](/details-cell/CL0000151) (CSI: 3.45), which underscores its importance in cells that process and secrete large quantities of glycoproteins. A consistent theme in its expression pattern is its high significance in mucus-producing cells across various tissues. This includes [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 3.15), [intestine goblet cell](/details-cell/CL0019031) (CSI: 2.88), [tracheal goblet cell](/details-cell/CL1000329) (CSI: 2.24), and [colon goblet cell](/details-cell/CL0009039) (CSI: 1.29). This pattern suggests that [SLC35C1](/details-gene/55343)-mediated fucosylation is a fundamental step in the biosynthesis and function of mucins, which are heavily glycosylated proteins critical for mucosal barrier integrity. Its high significance is also noted in other epithelial cells of the digestive tract, such as [foveolar cell of stomach](/details-cell/CL0002179) and [colonocyte](/details-cell/CL1000347), as well as in [stem cell](/details-cell/CL0000034) populations, suggesting a role in maintaining and differentiating these secretory lineages. ## Pathways and Molecular Function [SLC35C1](/details-gene/55343) is functionally annotated as a [GDP-fucose transmembrane transporter](/details-cell/GO:0005457) with [antiporter activity](/details-cell/GO:0015297), localized to the [Golgi membrane](/details-cell/GO:0000139). Its primary biological process is the [import of GDP-fucose into the Golgi lumen](/details-cell/GO:0036085), a rate-limiting step for fucosylation reactions. This activity is integral to multiple major pathways within the [Metabolism of proteins](/details-cell/R-HSA-392499) and [Post-translational protein modification](/details-cell/R-HSA-597592). It directly supports [Asparagine N-linked glycosylation](/details-cell/R-HSA-446203) and [Protein O-linked fucosylation](/details-cell/GO:0036066). The fucosylation of Notch receptors is a critical regulatory mechanism, and [SLC35C1](/details-gene/55343) is implicated in the [negative regulation of Notch signaling pathway](/details-cell/GO:0045746), which likely influences cell fate decisions, particularly in tissues with high cell turnover like the intestine. The clinical importance of this gene is explicitly captured by the Reactome pathway [Defective slc35c1 causes congenital disorder of glycosylation 2c (cdg2c)](https://reactome.org/content/detail/R-HSA-5619078), which falls under the broader categories of [SLC transporter disorders](/details-cell/R-HSA-5619102) and [Disorders of transmembrane transporters](/details-cell/R-HSA-5619115). ## Research Directions The well-defined role of [SLC35C1](/details-gene/55343) in fucosylation, coupled with its specific expression pattern, opens several avenues for further investigation. **Testable Hypotheses:** 1. Given its high expression in various [goblet cells](/details-cell/CL0000160), it is hypothesized that [SLC35C1](/details-gene/55343) activity is a critical regulator of mucin glycosylation and, consequently, the biophysical properties of the mucus barrier. Dysregulation of [SLC35C1](/details-gene/55343) in intestinal epithelial cells may be a contributing factor to the pathogenesis of inflammatory bowel disease by altering host-microbiome interactions. 2. The high significance of [SLC35C1](/details-gene/55343) in [stem cell](/details-cell/CL0000034) populations and its known role in regulating Notch signaling suggest a hypothesis that [SLC35C1](/details-gene/55343)-mediated fucosylation is a key determinant of cell fate in the intestinal crypt, guiding the differentiation of progenitor cells toward the secretory lineage (e.g., [goblet cells](/details-cell/CL0000160)) versus the absorptive lineage. **Proposed Experiment:** To test the hypothesis regarding its role in intestinal stem cell fate (Hypothesis 2), one could utilize an intestinal organoid culture system derived from Lgr5-EGFP-CreERT2 mice. A conditional knockout of [SLC35C1](/details-gene/55343) could be induced via tamoxifen treatment. The subsequent impact on cell lineage allocation would be assessed using single-cell RNA-sequencing to quantify changes in the proportions of stem cells, enterocytes, and secretory cells. This could be complemented by immunofluorescence staining for lineage markers (e.g., MUC2 for [goblet cells](/details-cell/CL0000160), CHGA for enteroendocrine cells) and functional assays to measure changes in Notch pathway activity (e.g., qPCR for Hes1). **Therapeutic Potential:** As [SLC35C1](/details-gene/55343) loss-of-function is the direct cause of the severe genetic disorder CDG-IIc/LAD-II, therapeutic strategies would logically focus on **restoring or augmenting** its function rather than inhibition. Its role as a transporter makes it a challenging target for small molecule activators, but it represents a prime candidate for gene therapy. A viral vector (e.g., AAV) designed to deliver a functional copy of the [SLC35C1](/details-gene/55343) gene to affected cell populations, such as hematopoietic stem cells or hepatocytes, could potentially correct the underlying molecular defect. However, the systemic nature of the disease presents a significant challenge for delivery and efficacy.

Genular Protein ID: 423961113

Symbol: FUCT1_HUMAN

Name: Solute carrier family 35 member C1

UniProtKB Accession Codes:

Q96A29 B2RDB2 Q9BV76 Q9NUJ8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 9 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 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 2 Pumba 1 RNAct 1 Reactome 3 RefSeq 3 Rhea 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11326279

Title: The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter.

PubMed ID: 11326279

DOI: 10.1038/ng0501-69

PubMed ID: 11326280

Title: Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency.

PubMed ID: 11326280

DOI: 10.1038/ng0501-73

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

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: 27738779

Title: Functional expression of a human GDP-L-fucose transporter in Escherichia coli.

PubMed ID: 27738779

DOI: 10.1007/s10529-016-2233-x

Sequence Information:

  • Length: 364
  • Mass: 39809
  • Checksum: 2E659D49C5C5E92E
  • Sequence:
    • MNRAPLKRSR ILHMALTGAS DPSAEAEANG EKPFLLRALQ IALVVSLYWV TSISMVFLNK 
YLLDSPSLRL DTPIFVTFYQ CLVTTLLCKG LSALAACCPG AVDFPSLRLD LRVARSVLPL 
SVVFIGMITF NNLCLKYVGV AFYNVGRSLT TVFNVLLSYL LLKQTTSFYA LLTCGIIIGG 
FWLGVDQEGA EGTLSWLGTV FGVLASLCVS LNAIYTTKVL PAVDGSIWRL TFYNNVNACI 
LFLPLLLLLG ELQALRDFAQ LGSAHFWGMM TLGGLFGFAI GYVTGLQIKF TSPLTHNVSG 
TAKACAQTVL AVLYYEETKS FLWWTSNMMV LGGSSAYTWV RGWEMKKTPE EPSPKDSEKS 
AMGV