Details for: SLC6A11

Gene ID: 6538

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: SLC6A11

Ensembl ID: ENSG00000132164

Description: solute carrier family 6 member 11

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mature astrocyte CL0002627
    CSI 3.67
    rCSI 15.59%
    PRS 78.71
  • glioblast CL0000030
    CSI 2.69
    rCSI 4.28%
    PRS 77.45
  • Mueller cell CL0000636
    CSI 2.6
    rCSI 5.93%
    PRS 77.89
  • amacrine cell CL0000561
    CSI 2.21
    rCSI 6.42%
    PRS 75.99
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.12
    rCSI 2.53%
    PRS 69.75
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.07
    rCSI 2.57%
    PRS 67.53
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2
    rCSI 3.54%
    PRS 69.18
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.82
    rCSI 2.34%
    PRS 70.79
  • inhibitory interneuron CL0000498
    CSI 1.76
    rCSI 4.06%
    PRS 74.82
  • extravillous trophoblast CL0008036
    CSI 1.73
    rCSI 2.14%
    PRS 83.87
  • ependymal cell CL0000065
    CSI 1.72
    rCSI 3.5%
    PRS 65.86
  • dopaminergic neuron CL0000700
    CSI 1.69
    rCSI 9.57%
    PRS 73.01
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.58
    rCSI 2.65%
    PRS 69.62
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.41
    rCSI 3.17%
    PRS 70.55
  • GABAergic amacrine cell CL4030027
    CSI 0.87
    rCSI 2.98%
    PRS 72.12
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.58
    rCSI 1.41%
    PRS 67.45
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.58
    rCSI 1.8%
    PRS 71.12
  • central nervous system neuron CL2000029
    CSI 0.55
    rCSI 4.01%
    PRS 74.72

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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Legend:
  • 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 [SLC6A11](/details-gene/6538), or Solute Carrier Family 6 Member 11, encodes the protein GAT-3, a sodium- and chloride-dependent gamma-aminobutyric acid (GABA) transporter. Its primary function is the reuptake of the inhibitory neurotransmitter GABA from the synaptic cleft, playing a critical role in terminating neurotransmission and maintaining inhibitory tone in the central nervous system. Expression data indicates that **Overall**, [SLC6A11](/details-gene/6538) is a highly significant marker for glial cells, particularly [mature astrocyte](/details-cell/CL0002627) and [Mueller cell](/details-cell/CL0000636), as well as various subtypes of GABAergic interneurons. Its prominent expression in these cell types underscores its central role in modulating neuronal excitability and synaptic function. ## Cellular Roles and Expression Landscape The expression profile of [SLC6A11](/details-gene/6538) highlights its specialized function within the central nervous system. **Overall**, the gene shows the highest significance in glial cell populations, with [mature astrocyte](/details-cell/CL0002627) (CSI: 3.67) exhibiting the most pronounced expression. This suggests that astrocytes are key regulators of extrasynaptic GABA concentration through GAT-3-mediated uptake. Other glial or glial-like cells, including [Mueller cell](/details-cell/CL0000636) (CSI: 2.60) in the retina and [ependymal cell](/details-cell/CL0000065) (CSI: 1.72), also show significant expression, pointing to a conserved role in GABA clearance across different CNS compartments. In addition to glial cells, [SLC6A11](/details-gene/6538) is a defining marker for multiple classes of inhibitory neurons. It is highly significant in [amacrine cell](/details-cell/CL0000561) (CSI: 2.21) and various cortical interneurons, such as [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 2.12) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.07). This dual expression pattern in both neurons and glia suggests [SLC6A11](/details-gene/6538) is involved in both presynaptic GABA reuptake to replenish neurotransmitter pools and perisynaptic uptake by astrocytes to shape inhibitory signals. Notably, [SLC6A11](/details-gene/6538) also shows high significance in [glioblast](/details-cell/CL0000030) (CSI: 2.69), a cell type associated with glioblastoma, indicating a potential role in the pathophysiology of brain tumors. The presence of [extravillous trophoblast](/details-cell/CL0008036) (CSI: 1.73) among the top expressing cells is an interesting finding, suggesting a potential, less-characterized role outside the nervous system. ## Pathways and Molecular Function The functional annotations for [SLC6A11](/details-gene/6538) are highly consistent with its observed expression in the nervous system. The gene is integral to the biological process of [Gamma-aminobutyric acid reuptake](/details-term/GO:0051936), a key step detailed in the Reactome pathway [Gaba synthesis, release, reuptake and degradation](/details-pathway/R-HSA-888590). Its molecular function is defined as [Gamma-aminobutyric acid:sodium:chloride symporter activity](/details-term/GO:0005332), which mechanistically places it within the family of [Na+/cl- dependent neurotransmitter transporters](/details-pathway/R-HSA-442660). Cellularly, the protein product is localized to the [plasma membrane](/details-term/GO:0005886), specifically at the [Gaba-ergic synapse](/details-term/GO:0098982), including both [presynaptic membrane](/details-term/GO:0042734) and [postsynaptic membrane](/details-term/GO:0045211) components. This localization is essential for its role in the [Neurotransmitter release cycle](/details-pathway/R-HSA-112310) and the broader process of [Transmission across chemical synapses](/details-pathway/R-HSA-112315). The transport activity also contributes to more general pathways such as [Slc-mediated transmembrane transport](/details-pathway/R-HSA-425407) and the [Transport of small molecules](/details-pathway/R-HSA-382551). This suite of functions solidifies its identity as a critical component for maintaining the precision and fidelity of inhibitory neurotransmission. ## Research Directions The expression data for [SLC6A11](/details-gene/6538) points toward several compelling areas for future investigation, particularly regarding its roles in neurological disease and cancer. Based on the available data, the following testable hypotheses can be proposed: 1. The high expression of [SLC6A11](/details-gene/6538) in [glioblast](/details-cell/CL0000030) cells actively contributes to tumor progression by modulating the peritumoral GABAergic environment, thereby promoting cell survival, proliferation, or invasion. 2. Astrocytic [SLC6A11](/details-gene/6538) is the primary regulator of extrasynaptic GABA tone in the cortex. Its dysregulation may be a key pathogenic mechanism in disorders of neural hyperexcitability, such as epilepsy, by failing to adequately buffer synaptic GABA spillover. A key experiment to test the first hypothesis regarding glioblastoma could be designed as follows: - **Experimental Design:** To investigate the functional role of [SLC6A11](/details-gene/6538) in glioblastoma, CRISPR-Cas9 technology could be used to knock out the gene in patient-derived glioblastoma stem cell (GSC) lines. The impact of [SLC6A11](/details-gene/6538) deletion on key cancer hallmarks would be assessed *in vitro*. Proliferation rates could be measured using cell counting assays, while invasive potential could be quantified using Matrigel invasion assays. Furthermore, these engineered GSC lines (knockout vs. wild-type control) could be xenografted into immunodeficient mice to evaluate the effect of [SLC6A11](/details-gene/6538) loss on tumor growth and animal survival *in vivo*. **Therapeutic Potential:** [SLC6A11](/details-gene/6538) represents a potentially valuable therapeutic target. As a solute carrier, it is a member of a druggable class of membrane proteins. Given its high expression in [glioblast](/details-cell/CL0000030) cells compared to many other cell types, a strategy of **inhibition** could be explored. A small molecule inhibitor designed to selectively block GAT-3 function might disrupt the ability of glioma cells to manipulate their microenvironment, potentially reducing their fitness and sensitizing them to radiation or chemotherapy. However, a major challenge would be achieving high specificity for the transporter on tumor cells versus its essential function in healthy neurons and astrocytes, which would be critical to minimize neurological side effects.

Genular Protein ID: 6552599

Symbol: S6A11_HUMAN

Name: Sodium- and chloride-dependent GABA transporter 3

UniProtKB Accession Codes:

P48066 B2R6U6 Q8IYC9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EMBL 6 Ensembl 2 GO 15 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 2 Rhea 8 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7874447

Title: Cloning of the human homologue of the GABA transporter GAT-3 and identification of a novel inhibitor with selectivity for this site.

PubMed ID: 7874447

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

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: 632
  • Mass: 70606
  • Checksum: D75C5B988E983278
  • Sequence:
    • MTAEKALPLG NGKAAEEARE SEAPGGGCSS GGAAPARHPR VKRDKAVHER GHWNNKVEFV 
LSVAGEIIGL GNVWRFPYLC YKNGGGAFLI PYVVFFICCG IPVFFLETAL GQFTSEGGIT 
CWRKVCPLFE GIGYATQVIE AHLNVYYIII LAWAIFYLSN CFTTELPWAT CGHEWNTENC 
VEFQKLNVSN YSHVSLQNAT SPVMEFWEHR VLAISDGIEH IGNLRWELAL CLLAAWTICY 
FCIWKGTKST GKVVYVTATF PYIMLLILLI RGVTLPGASE GIKFYLYPDL SRLSDPQVWV 
DAGTQIFFSY AICLGCLTAL GSYNNYNNNC YRDCIMLCCL NSGTSFVAGF AIFSVLGFMA 
YEQGVPIAEV AESGPGLAFI AYPKAVTMMP LSPLWATLFF MMLIFLGLDS QFVCVESLVT 
AVVDMYPKVF RRGYRRELLI LALSVISYFL GLVMLTEGGM YIFQLFDSYA ASGMCLLFVA 
IFECICIGWV YGSNRFYDNI EDMIGYRPPS LIKWCWMIMT PGICAGIFIF FLIKYKPLKY 
NNIYTYPAWG YGIGWLMALS SMLCIPLWIC ITVWKTEGTL PEKLQKLTTP STDLKMRGKL 
GVSPRMVTVN DCDAKLKSDG TIAAITEKET HF