Details for: SLC13A2

Gene ID: 9058

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: SLC13A2

Ensembl ID: ENSG00000007216

Description: solute carrier family 13 member 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • colonocyte CL1000347
    CSI 6.18
    rCSI 8.85%
    PRS 98.49
  • intestinal epithelial cell CL0002563
    CSI 6.04
    rCSI 6.31%
    PRS 98.25
  • intestine goblet cell CL0019031
    CSI 4.64
    rCSI 4.12%
    PRS 98.22
  • secretory cell CL0000151
    CSI 4.09
    rCSI 4.27%
    PRS 98.47
  • tracheobronchial serous cell CL0019001
    CSI 3.7
    rCSI 15.98%
    PRS 98.87
  • goblet cell CL0000160
    CSI 3.4
    rCSI 3.21%
    PRS 98.32
  • colon epithelial cell CL0011108
    CSI 2.81
    rCSI 2.95%
    PRS 98.5
  • enterocyte CL0000584
    CSI 2.56
    rCSI 4.13%
    PRS 97.63
  • epithelial cell of proximal tubule CL0002306
    CSI 2.46
    rCSI 6.01%
    PRS 96.42
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.92
    rCSI 5.18%
    PRS 99.14
  • enterocyte of epithelium of small intestine CL1000334
    CSI 1.35
    rCSI 20.89%
    PRS 98.85
  • transit amplifying cell of small intestine CL0009012
    CSI 1.17
    rCSI 5.11%
    PRS 99.18
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.16
    rCSI 3.25%
    PRS 99.16

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
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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 [SLC13A2](/details-gene/9058), or Solute Carrier Family 13 Member 2, encodes a sodium-dicarboxylate cotransporter known as NaDC1. This protein is primarily responsible for the sodium-dependent transport of Krebs cycle intermediates, such as citrate, succinate, alpha-ketoglutarate, and fumarate, across the plasma membrane. Expression data indicates that [SLC13A2](/details-gene/9058) is a highly significant gene in absorptive epithelial tissues, with its highest expression and functional importance observed in the gastrointestinal tract, particularly in [colonocyte](/details-cell/CL1000347)s and [intestinal epithelial cell](/details-cell/CL0002563)s, as well as in the [epithelial cell of proximal tubule](/details-cell/CL0002306)s of the kidney. Its primary role is to mediate the reabsorption of key metabolites from the gut lumen and renal filtrate. ## Cellular Roles and Expression Landscape The expression profile of [SLC13A2](/details-gene/9058) firmly establishes its role as a specialized transporter in epithelial tissues responsible for nutrient and metabolite handling. **Overall**, the gene shows its highest significance in a range of intestinal epithelial cell types. It is a top marker for [colonocyte](/details-cell/CL1000347) (CSI: 6.18) and the broader category of [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 6.04). Its high significance extends to secretory lineages within the gut, such as the [intestine goblet cell](/details-cell/CL0019031) (CSI: 4.64), and progenitor cells like the [intestinal crypt stem cell of small intestine](/details-cell/CL0009017) (CSI: 1.92). This distribution suggests a fundamental role in maintaining metabolic homeostasis throughout the intestinal epithelium, from absorption in mature [enterocyte](/details-cell/CL0000584)s to supporting the high metabolic demands of stem and transit-amplifying cells. Beyond the intestine, [SLC13A2](/details-gene/9058) is also significantly expressed in the [epithelial cell of proximal tubule](/details-cell/CL0002306) of the kidney (CSI: 2.46). This is consistent with its initial characterization as a renal transporter responsible for reabsorbing dicarboxylates from the glomerular filtrate, thereby preventing the loss of valuable metabolic intermediates [Link](https://doi.org/10.1152/ajprenal.1996.270.4.f642). The collective data paints a picture of a gene with a highly specific function restricted to the apical membrane of polarized epithelial cells in the gut and kidney. ## Pathways and Molecular Function The molecular functions of [SLC13A2](/details-gene/9058) are well-defined and center on its role as a secondary active transporter. It is a key component of SLC-mediated transmembrane transport pathways, including '[Slc-mediated transmembrane transport](/details-reactome/R-HSA-425407)' and, more specifically, '[Sodium-coupled sulphate, di- and tri-carboxylate transporters](/details-reactome/R-HSA-433137)'. Functionally, it exhibits '[sodium:dicarboxylate symporter activity](/details-go/GO:0017153)', coupling the inwardly-directed sodium gradient to the uptake of dicarboxylates. Gene Ontology annotations highlight its activity with several specific substrates, including '[alpha-ketoglutarate transmembrane transporter activity](/details-go/GO:0015139)', '[fumarate transmembrane transporter activity](/details-go/GO:0015138)', and '[succinate transmembrane transporter activity](/details-go/GO:0015141)'. These biological processes are critical for cellular energy metabolism. This transport function occurs predominantly at the '[apical plasma membrane](/details-go/GO:0016324)', a localization essential for its role in absorbing substrates from the external environment (i.e., the lumen of the intestine or kidney tubule). In [colonocyte](/details-cell/CL1000347)s, this activity allows for the uptake of metabolites produced by the gut microbiota, while in the kidney, it is a primary mechanism for metabolite reabsorption [Link](https://doi.org/10.1152/ajprenal.2000.279.1.f54). ## Research Directions The specific expression pattern and critical metabolic function of [SLC13A2](/details-gene/9058) suggest its involvement in both physiological homeostasis and pathology, particularly in metabolic disorders and cancer. Based on the available data, several testable hypotheses can be proposed: 1. **Role in Kidney Stone Disease:** Given that [SLC13A2](/details-gene/9058) transports citrate and genetic associations have been reported [Link](https://doi.org/10.1111/j.1442-2042.2007.01554.x), it is hypothesized that functional polymorphisms in the [SLC13A2](/details-gene/9058) gene directly alter citrate reabsorption efficiency in [epithelial cell of proximal tubule](/details-cell/CL0002306)s. Variants leading to reduced function would increase urinary citrate excretion, potentially offering protection against calcium-based kidney stone formation. 2. **Modulation of Host-Microbiome Interactions:** In the colon, metabolites like succinate and alpha-ketoglutarate are key signaling molecules between the host and microbiome. It can be hypothesized that altered expression or activity of [SLC13A2](/details-gene/9058) in [colonocyte](/details-cell/CL1000347)s changes the availability of these microbial-derived metabolites to the host epithelium, thereby influencing immune cell function and contributing to the pathogenesis of inflammatory bowel disease. 3. **Metabolic Reprogramming in Cancer:** Research indicates that [SLC13A2](/details-gene/9058) expression is maintained or potentially altered in neoplastic kidney tissues [Link](https://doi.org/10.1152/ajprenal.00559.2016). We hypothesize that in certain metabolic subtypes of renal cell carcinoma, upregulation of [SLC13A2](/details-gene/9058) serves as a critical mechanism for scavenging Krebs cycle intermediates from the filtrate to fuel anabolic pathways and support tumor proliferation. To test the hypothesis regarding its role in cancer, a key experiment could be designed. * **Proposed Experiment:** To determine if renal cell carcinoma (RCC) is dependent on [SLC13A2](/details-gene/9058) for metabolic support, one could use CRISPR-Cas9 to knock out the gene in RCC cell lines that show high endogenous expression. The metabolic impact could then be quantified using stable isotope tracing with 13C-labeled succinate or alpha-ketoglutarate, followed by mass spectrometry. Furthermore, the effect of [SLC13A2](/details-gene/9058) knockout on cell proliferation, survival under nutrient stress, and in vivo tumor growth in xenograft mouse models would directly test its functional necessity in this context. Given its specific role in nutrient uptake and its accessibility on the plasma membrane, [SLC13A2](/details-gene/9058) may hold therapeutic potential. If found to be a key metabolic dependency in cancers like RCC, **inhibition** would be the therapeutic strategy. A specific small-molecule inhibitor could selectively block this transport activity, potentially starving cancer cells of essential metabolites. However, the high expression of [SLC13A2](/details-gene/9058) in healthy kidney and intestinal tissues suggests that on-target toxicities would be a significant concern, requiring a careful therapeutic window or targeted delivery approach.

Genular Protein ID: 586401321

Symbol: S13A2_HUMAN

Name: Solute carrier family 13 member 2

UniProtKB Accession Codes:

Q13183 B2RBI9 B4DPL1 E7ETH5 Q4VAR7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 6 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 EMBL 7 EMDB 3 Ensembl 2 ExpressionAtlas 1 GO 13 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 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 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 2 Rhea 3 SABIO-RK 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8967342

Title: Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney.

PubMed ID: 8967342

DOI: 10.1152/ajprenal.1996.270.4.f642

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 9668069

Title: Sodium and lithium interactions with the Na+/Dicarboxylate cotransporter.

PubMed ID: 9668069

DOI: 10.1074/jbc.273.30.18923

PubMed ID: 10894787

Title: The transport properties of the human renal Na(+)- dicarboxylate cotransporter under voltage-clamp conditions.

PubMed ID: 10894787

DOI: 10.1152/ajprenal.2000.279.1.f54

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: 27927654

Title: Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney.

PubMed ID: 27927654

DOI: 10.1152/ajprenal.00559.2016

PubMed ID: 17470169

Title: Associations between renal sodium-citrate cotransporter (hNaDC-1) gene polymorphism and urinary citrate excretion in recurrent renal calcium stone formers and normal controls.

PubMed ID: 17470169

DOI: 10.1111/j.1442-2042.2007.01554.x

Sequence Information:

  • Length: 592
  • Mass: 64410
  • Checksum: 41137D6621A0872A
  • Sequence:
    • MATCWQALWA YRSYLIVFFV PILLLPLPIL VPSKEAYCAY AIILMALFWC TEALPLAVTA 
LFPLILFPMM GIVDASEVAV EYLKDSNLLF FGGLLVAIAV EHWNLHKRIA LRVLLIVGVR 
PAPLILGFML VTAFLSMWIS NTATSAMMVP IAHAVLDQLH SSQASSNVEE GSNNPTFELQ 
EPSPQKEVTK LDNGQALPVT SASSEGRAHL SQKHLHLTQC MSLCVCYSAS IGGIATLTGT 
APNLVLQGQI NSLFPQNGNV VNFASWFSFA FPTMVILLLL AWLWLQILFL GFNFRKNFGI 
GEKMQEQQQA AYCVIQTEHR LLGPMTFAEK AISILFVILV LLWFTREPGF FLGWGNLAFP 
NAKGESMVSD GTVAIFIGII MFIIPSKFPG LTQDPENPGK LKAPLGLLDW KTVNQKMPWN 
IVLLLGGGYA LAKGSERSGL SEWLGNKLTP LQSVPAPAIA IILSLLVATF TECTSNVATT 
TIFLPILASM AQAICLHPLY VMLPCTLATS LAFMLPVATP PNAIVFSFGD LKVLDMARAG 
FLLNIIGVLI IALAINSWGI PLFSLHSFPS WAQSNTTAQC LPSLANTTTP SP

Genular Protein ID: 2152627630

Symbol: J3QL78_HUMAN

Name: N/A

UniProtKB Accession Codes:

J3QL78

Database IDs:

ARBA 7 CDD 1 CTD 1 ChiTaRS 1 EMBL 1 Ensembl 2 GO 2 GeneTree 1 HGNC 1 InterPro 2 NCBI Taxonomy 1 PANTHER 2 PROSITE 1 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 2 SMR 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 548
  • Mass: 59353
  • Checksum: D59A54D2C72F1BD7
  • Sequence:
    • MALFWCTEAL PLAVTALFPL ILFPMMGIVD ASEVAVEYLK DSNLLFFGGL LVAIAVEHWN 
LHKRIALRVL LIVGVRPAPL ILGFMLVTAF LSMWISNTAT SAMMVPIAHA VLDQLHSSQA 
SSNVEEGSNN PTFELQEPSP QKEVTKLDNG QALPVTSASS EGRAHLSQKH LHLTQCMSLC 
VCYSASIGGI ATLTGTAPNL VLQGQINSLF PQNGNVVNFA SWFSFAFPTM VILLLLAWLW 
LQILFLGFNF RKNFGIGEKM QEQQQAAYCV IQTEHRLLGP MTFAEKAISI LFVILVLLWF 
TREPGFFLGW GNLAFPNAKG ESMVSDGTVA IFIGIIMFII PSKFPGLTQD PENPGKLKAP 
LGLLDWKTVN QKMPWNIVLL LGGGYALAKG SERSGLSEWL GNKLTPLQSV PAPAIAIILS 
LLVATFTECT SNVATTTIFL PILASMAQAI CLHPLYVMLP CTLATSLAFM LPVATPPNAI 
VFSFGDLKVL DMARAGFLLN IIGVLIIALA INSWGIPLFS LHSFPSWAQS NTTAQCLPSL 
ANTTTPSP