Details for: SLC23A1

Gene ID: 9963

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: SLC23A1

Ensembl ID: ENSG00000170482

Description: solute carrier family 23 member 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 8.77
    rCSI 7.71%
    PRS 98.8
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 3.79
    rCSI 9.2%
    PRS 98.12
  • ciliated cell CL0000064
    CSI 3.41
    rCSI 5.53%
    PRS 98.74
  • enterocyte CL0000584
    CSI 3.2
    rCSI 5.16%
    PRS 99.22
  • epithelial cell of proximal tubule CL0002306
    CSI 3.01
    rCSI 7.36%
    PRS 98.61
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.23
    rCSI 5.08%
    PRS 98.75

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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    • High
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  • 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 [SLC23A1](/details-gene/9963), or Solute Carrier Family 23 Member 1, encodes the sodium-dependent vitamin C transporter 1 (SVCT1). This protein is a critical component for maintaining systemic vitamin C homeostasis by facilitating the active transport of L-ascorbic acid across the plasma membrane. Its function is essential for the uptake and reabsorption of vitamin C in specialized epithelial tissues. Expression data indicates that **Overall**, [SLC23A1](/details-gene/9963) is a highly significant marker for polarized epithelial cells, particularly [ciliated epithelial cells](/details-cell/CL0000067) in the respiratory tract, [enterocytes](/details-cell/CL0000584) in the intestine, and [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney. This expression pattern aligns with its primary role in nutrient transport and its established involvement in processes like [L-ascorbic acid transmembrane transport](/details-cell/GO:0015882). ## Cellular Roles and Expression Landscape The expression profile of [SLC23A1](/details-gene/9963) highlights its specialized function in tissues that form a barrier and are involved in active transport. **Overall**, its most significant expression is observed in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 8.77), [ciliated cell](/details-cell/CL0000064), and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145), underscoring a vital role in the respiratory system. This suggests that maintaining high intracellular vitamin C levels is a key feature of these cells, possibly for protection against oxidative damage from inhaled pathogens and pollutants. In addition to the respiratory tract, [SLC23A1](/details-gene/9963) is a key transporter in other critical epithelial tissues responsible for nutrient absorption and reabsorption. Its high significance in [enterocytes](/details-cell/CL0000584) of the intestine and [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney is consistent with the established role of SVCT1 in dietary vitamin C uptake and renal vitamin C reclamation, respectively ([Link](https://doi.org/10.1080/09687680110033774)). Interestingly, a notable expression is also detected in [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040), which aligns with functional annotations related to [brain development](/details-cell/GO:0007420) and suggests a role for vitamin C transport in neuronal function and protection. ## Pathways and Molecular Function The molecular function of [SLC23A1](/details-gene/9963) is centered on its activity as a sodium-ion symporter. Functional annotations confirm its role in [L-ascorbate:sodium symporter activity](/details-cell/GO:0008520) and [L-ascorbic acid transmembrane transporter activity](/details-cell/GO:0015229). These activities are integral to the Reactome pathway for [Vitamin c (ascorbate) metabolism](/details-cell/R-HSA-196836). The protein is predominantly localized to the [plasma membrane](/details-cell/GO:0005886), with specific enrichment in the [apical plasma membrane](/details-cell/GO:0016324) and [basal plasma membrane](/details-cell/GO:0009925), which is crucial for vectorial transport across epithelial cell layers ([Link](https://doi.org/10.1016/j.yexcr.2009.04.007)). Beyond its canonical role in vitamin C transport, recent evidence suggests a broader substrate specificity. [SLC23A1](/details-gene/9963) is also implicated in [urate transport](/details-cell/GO:0015747) and [nucleobase transport](/details-cell/GO:0015851), with one study identifying it as a physiological urate importer ([Link](https://doi.org/10.1007/s00424-023-02792-1)). This dual function connects vitamin C homeostasis with purine metabolism, particularly in the kidney where both urate and vitamin C levels are tightly regulated. ## Research Directions The data highlights the specialized roles of [SLC23A1](/details-gene/9963) in specific cell types, opening avenues for further investigation into its physiological and pathological importance. **Proposed Hypotheses:** 1. Given its exceptionally high significance in respiratory [ciliated epithelial cells](/details-cell/CL0000067) and its link to [lung development](/details-cell/GO:0030324), [SLC23A1](/details-gene/9963)-mediated vitamin C accumulation is likely essential for ciliogenesis and/or protecting ciliated cells from oxidative stress, and its dysfunction may contribute to the pathogenesis of chronic respiratory diseases like COPD. 2. The significant expression in [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) suggests that [SLC23A1](/details-gene/9963) is critical for supplying ascorbic acid to these specific neurons, potentially to modulate glutamatergic signaling or protect against excitotoxicity, a common mechanism in neurodegenerative disorders. 3. The dual function of [SLC23A1](/details-gene/9963) as both a vitamin C transporter and a urate importer ([Link](https://doi.org/10.1007/s00424-023-02792-1)) in the [epithelial cell of proximal tubule](/details-cell/CL0002306) suggests that its transport activity may represent a molecular link between vitamin C status and serum urate levels. Genetic polymorphisms affecting its function could therefore be risk factors for hyperuricemia and gout. **Experimental Approach:** To test the hypothesis regarding its role in respiratory ciliated cells, an *in vitro* model using primary human bronchial epithelial cells differentiated at an air-liquid interface (ALI) would be appropriate. [SLC23A1](/details-gene/9963) expression could be silenced using CRISPR interference (CRISPRi). The impact on cellular function would be assessed by quantifying ciliary length and density via immunofluorescence staining for acetylated tubulin, measuring ciliary beat frequency with high-speed video microscopy, and evaluating the cell's capacity to handle oxidative stress (e.g., after exposure to cigarette smoke extract) by measuring ROS levels and cell viability. **Therapeutic Potential:** As a cell surface transporter, [SLC23A1](/details-gene/9963) is a potentially druggable target. Strategies aimed at **activation** or enhancing its expression could be explored for therapeutic benefit in conditions associated with oxidative stress and localized vitamin C deficiency, such as in the lungs of smokers or patients with chronic inflammatory lung disease. Conversely, selective **inhibition** of its urate transport function, if possible without affecting vitamin C uptake, could present a novel strategy for managing hyperuricemia. However, any inhibitory approach must be carefully evaluated due to the essential role of [SLC23A1](/details-gene/9963) in systemic vitamin C homeostasis, where broad inhibition would likely be detrimental.

Genular Protein ID: 871192718

Symbol: S23A1_HUMAN

Name: Na(+)/L-ascorbic acid transporter 1

UniProtKB Accession Codes:

Q9UHI7 O95191 Q8WWB6 Q9UGH4 Q9UI39

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EMBL 10 EMDB 3 Ensembl 2 ExpressionAtlas 1 GO 20 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 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 PDB 4 PDBsum 4 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 2 Rhea 4 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9804989

Title: Molecular characterization of two novel transporters from human and mouse kidney and from LLC-PK1 cells reveals a novel conserved family that is homologous to bacterial and Aspergillus nucleobase transporters.

PubMed ID: 9804989

DOI: 10.1016/s0167-4781(98)00151-1

PubMed ID: 10556483

Title: Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant.

PubMed ID: 10556483

DOI: 10.1016/s0005-2736(99)00182-0

PubMed ID: 10556521

Title: Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2.

PubMed ID: 10556521

DOI: 10.1016/s0014-5793(99)01393-9

PubMed ID: 10631088

Title: Human vitamin C (L-ascorbic acid) transporter SVCT1.

PubMed ID: 10631088

DOI: 10.1006/bbrc.1999.1929

PubMed ID: 11584081

Title: Characterization of the genomic structure of the human vitamin C transporter SVCT1 (SLC23A2).

PubMed ID: 11584081

DOI: 10.1093/jn/131.10.2623

PubMed ID: 11396616

Title: Vitamin C transport systems of mammalian cells.

PubMed ID: 11396616

DOI: 10.1080/09687680110033774

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 19379732

Title: Topological studies of hSVCT1, the human sodium-dependent vitamin C transporter and the influence of N-glycosylation on its intracellular targeting.

PubMed ID: 19379732

DOI: 10.1016/j.yexcr.2009.04.007

PubMed ID: 36749388

Title: Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations.

PubMed ID: 36749388

DOI: 10.1007/s00424-023-02792-1

Sequence Information:

  • Length: 598
  • Mass: 64815
  • Checksum: 939C52B9D1157029
  • Sequence:
    • MRAQEDLEGR TQHETTRDPS TPLPTEPKFD MLYKIEDVPP WYLCILLGFQ HYLTCFSGTI 
AVPFLLAEAL CVGHDQHMVS QLIGTIFTCV GITTLIQTTV GIRLPLFQAS AFAFLVPAKA 
ILALERWKCP PEEEIYGNWS LPLNTSHIWH PRIREVQGAI MVSSVVEVVI GLLGLPGALL 
NYIGPLTVTP TVSLIGLSVF QAAGDRAGSH WGISACSILL IILFSQYLRN LTFLLPVYRW 
GKGLTLLRIQ IFKMFPIMLA IMTVWLLCYV LTLTDVLPTD PKAYGFQART DARGDIMAIA 
PWIRIPYPCQ WGLPTVTAAA VLGMFSATLA GIIESIGDYY ACARLAGAPP PPVHAINRGI 
FTEGICCIIA GLLGTGNGST SSSPNIGVLG ITKVGSRRVV QYGAAIMLVL GTIGKFTALF 
ASLPDPILGG MFCTLFGMIT AVGLSNLQFV DMNSSRNLFV LGFSMFFGLT LPNYLESNPG 
AINTGILEVD QILIVLLTTE MFVGGCLAFI LDNTVPGSPE ERGLIQWKAG AHANSDMSSS 
LKSYDFPIGM GIVKRITFLK YIPICPVFKG FSSSSKDQIA IPEDTPENTE TASVCTKV