Details for: SLC5A12

Gene ID: 159963

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: SLC5A12

Ensembl ID: ENSG00000148942

Description: solute carrier family 5 member 12

Cell Significance Landscape

Associated with

Significant Cells

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

  • intestinal epithelial cell CL0002563
    CSI 20.99
    rCSI 21.94%
    PRS 85.27
  • renal beta-intercalated cell CL0002201
    CSI 7.73
    rCSI 18.43%
    PRS 87.61
  • cardiac muscle cell CL0000746
    CSI 6.05
    rCSI 8.69%
    PRS 79.05
  • enterocyte CL0000584
    CSI 5.94
    rCSI 9.58%
    PRS 85.01
  • colonocyte CL1000347
    CSI 5.82
    rCSI 8.34%
    PRS 86.52
  • epithelial cell of proximal tubule CL0002306
    CSI 5.18
    rCSI 12.66%
    PRS 80.59
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 5.11
    rCSI 13.32%
    PRS 88.93
  • mononuclear phagocyte CL0000113
    CSI 5.05
    rCSI 11.12%
    PRS 90.3
  • parietal epithelial cell CL1000452
    CSI 4.97
    rCSI 13.27%
    PRS 81.2
  • renal interstitial pericyte CL1001318
    CSI 4.47
    rCSI 12.33%
    PRS 84.19
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 3.21
    rCSI 34.01%
    PRS 77.39
  • regular atrial cardiac myocyte CL0002129
    CSI 1.68
    rCSI 5.42%
    PRS 84.33
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 1.37
    rCSI 10.88%
    PRS 83.39
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.19
    rCSI 12.57%
    PRS 83.72
  • podocyte CL0000653
    CSI 1.17
    rCSI 5.18%
    PRS 88.34
  • kidney connecting tubule epithelial cell CL1000768
    CSI 0.85
    rCSI 2.15%
    PRS 80.27
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.46
    rCSI 7.16%
    PRS 91.65

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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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • 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 [SLC5A12](/details-gene/159963) is a protein-coding gene located on chromosome 11 that encodes a member of the solute carrier family 5, designated Solute Carrier Family 5 Member 12. Functionally, it operates as an electroneutral sodium-monocarboxylate cotransporter, playing a critical role in the transport of small organic acids, such as lactate, across the plasma membrane. Expression data indicates that **Overall**, [SLC5A12](/details-gene/159963) is most significantly and specifically expressed in epithelial tissues, particularly in the intestine and kidney, suggesting a primary role in nutrient absorption and metabolic homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [SLC5A12](/details-gene/159963) highlights its specialized function in epithelial transport. **Overall**, the gene shows exceptionally high significance in [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 20.99), underscoring a critical role in the absorption of monocarboxylates from the gut lumen. A second major site of function is the kidney, where it is a significant marker across multiple specialized cell types. These include [renal beta-intercalated cell](/details-cell/CL0002201) (CSI: 7.73), [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 5.18), and [kidney proximal convoluted tubule epithelial cell](/details-cell/CL1000838) (CSI: 3.21). This expression pattern is consistent with its known role in the reabsorption of lactate and other monocarboxylates from the glomerular filtrate, a key process for energy conservation and acid-base balance, as established in functional characterization studies [Link](https://doi.org/10.1016/j.bbamem.2007.06.031). Interestingly, significant expression is also noted in [cardiac muscle cell](/details-cell/CL0000746) (CSI: 6.05), suggesting a potential role in lactate handling within cardiomyocytes, which is crucial for cardiac energy metabolism, especially under ischemic conditions. The gene also shows relevance in certain phagocytic and structural cells, such as [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695) (CSI: 5.11) and [renal interstitial pericyte](/details-cell/CL1001318) (CSI: 4.47), although its function in these contexts is less defined. The collective data points to [SLC5A12](/details-gene/159963) as a key transporter in tissues with high metabolic turnover and transport activity. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [SLC5A12](/details-gene/159963) are tightly linked to its role as a transporter. Gene Ontology annotations confirm its involvement in processes such as [Lactate transmembrane transport](/details-ontology/GO:0035873), [Monocarboxylic acid transport](/details-ontology/GO:0015718), and [Sodium ion transport](/details-ontology/GO:0006814). Its molecular function is defined as [Monocarboxylate:sodium symporter activity](/details-ontology/GO:0140161), indicating that it cotransports monocarboxylates with sodium ions down their electrochemical gradient. Consistent with its function as a transporter in epithelial layers, [SLC5A12](/details-gene/159963) is predominantly localized to the [Apical plasma membrane](/details-ontology/GO:0016324). This specific localization is essential for its role in vectorial transport, moving substrates from the lumen of the intestine or kidney tubules into the cell. The Reactome pathway database further classifies its activity within broader themes of transmembrane transport, including [Slc-mediated transmembrane transport](/details-pathway/R-HSA-425407) and the overarching category of [Transport of small molecules](/details-pathway/R-HSA-382551). This functional profile aligns perfectly with its high expression in the absorptive and reabsorptive epithelia of the intestine and kidneys. ## Research Directions The specific expression pattern and function of [SLC5A12](/details-gene/159963) offer several avenues for future investigation, particularly concerning metabolic diseases and organ-specific pathology. **Testable Hypotheses:** 1. **Role in Kidney Disease:** Given its high expression in the [epithelial cell of proximal tubule](/details-cell/CL0002306), it is hypothesized that dysregulation of [SLC5A12](/details-gene/159963) contributes to altered lactate metabolism and acid-base imbalance observed in chronic kidney disease (CKD), potentially exacerbating tubular injury. 2. **Gut Microbiome Interaction:** The premier expression of [SLC5A12](/details-gene/159963) in [intestinal epithelial cell](/details-cell/CL0002563) suggests it may be a key interface between the host and the gut microbiome. We hypothesize that its expression or activity is modulated by microbial-derived short-chain fatty acids (SCFAs), such as butyrate, thereby influencing intestinal energy homeostasis and inflammatory responses. 3. **Cardiac Metabolism:** The significant expression in [cardiac muscle cell](/details-cell/CL0000746) warrants investigation into its role in cardiac pathophysiology. It is hypothesized that [SLC5A12](/details-gene/159963) is upregulated during myocardial ischemia to increase lactate uptake as an alternative fuel source, representing a potential adaptive mechanism. **Proposed Experimental Approach:** To test the hypothesis regarding its role in chronic kidney disease (Hypothesis 1), a mouse model of CKD, such as adenine-induced nephropathy, could be utilized. The expression level and subcellular localization of [SLC5A12](/details-gene/159963) in the proximal tubules of CKD mice would be compared to healthy controls using quantitative PCR, western blotting, and immunofluorescence microscopy. Furthermore, a genetic knockout of *Slc5a12* in this model would allow for the direct assessment of its contribution to disease progression, monitored by measuring serum creatinine, blood urea nitrogen, and urinary lactate levels. **Therapeutic Potential:** As a plasma membrane transporter, [SLC5A12](/details-gene/159963) is a potentially "druggable" target. Its high specificity for kidney and intestinal epithelia could allow for targeted therapeutic intervention. For certain metabolic disorders characterized by excessive lactate reabsorption, such as some forms of lactic acidosis, selective **inhibition** of [SLC5A12](/details-gene/159963) could be a viable therapeutic strategy to promote lactate excretion. Conversely, in conditions involving impaired transport of key monocarboxylates like butyrate in the colon, small molecule **activators** of [SLC5A12](/details-gene/159963) could be explored to enhance nutrient absorption and support epithelial health. However, the potential for off-target effects in the heart and other expressing tissues would require careful evaluation.

Genular Protein ID: 3511039429

Symbol: SC5AC_HUMAN

Name: Electroneutral sodium monocarboxylate cotransporter

UniProtKB Accession Codes:

Q1EHB4 Q86UC7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 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 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 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 1 Rhea 6 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: 17692818

Title: Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney.

PubMed ID: 17692818

DOI: 10.1016/j.bbamem.2007.06.031

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

Sequence Information:

  • Length: 618
  • Mass: 67647
  • Checksum: 01D5F954BD28EF6F
  • Sequence:
    • MEVKNFAVWD YVVFAALFFI SSGIGVFFAI KERKKATSRE FLVGGRQMSF GPVGLSLTAS 
FMSAVTVLGT PSEVYRFGAS FLVFFIAYLF VILLTSELFL PVFYRSGITS TYEYLQLRFN 
KPVRYAATVI YIVQTILYTG VVVYAPALAL NQVTGFDLWG SVFATGIVCT FYCTLGGLKA 
VVWTDAFQMV VMIVGFLTVL IQGSTHAGGF HNVLEQSTNG SRLHIFDFDV DPLRRHTFWT 
ITVGGTFTWL GIYGVNQSTI QRCISCKTEK HAKLALYFNL LGLWIILVCA VFSGLIMYSH 
FKDCDPWTSG IISAPDQLMP YFVMEIFATM PGLPGLFVAC AFSGTLSTVA SSINALATVT 
FEDFVKSCFP HLSDKLSTWI SKGLCLLFGV MCTSMAVAAS VMGGVVQASL SIHGMCGGPM 
LGLFSLGIVF PFVNWKGALG GLLTGITLSF WVAIGAFIYP APASKTWPLP LSTDQCIKSN 
VTATGPPVLS SRPGIADTWY SISYLYYSAV GCLGCIVAGV IISLITGRQR GEDIQPLLIR 
PVCNLFCFWS KKYKTLCWCG VQHDSGTEQE NLENGSARKQ GAESVLQNGL RRESLVHVPG 
YDPKDKSYNN MAFETTHF