SLC1A6 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6
Description	Enables L-aspartate transmembrane transporter activity; L-glutamate transmembrane transporter activity; and glutamate:sodium symporter activity. Involved in L-aspartate import across plasma membrane; L-glutamate import across plasma membrane; and neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC1A6 encodes the EAAT4 protein, a postsynaptic excitatory amino acid transporter primarily expressed in cerebellar Purkinje cells that plays a dual role in clearing extracellular glutamate and mediating an associated chloride conductance. Biophysical studies reveal that EAAT4 operates by coupling sodium‐driven glutamate uptake with an anion channel function, and that each subunit within its trimer contributes independently to this gating mechanism rather than acting cooperatively."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its core transporter/channel activity, EAAT4 function is under complex regulatory control. In Purkinje cells, the abundance and activity of EAAT4 can be modulated by phosphorylation events—such as those mediated by serum and glucocorticoid inducible kinase 1 (SGK1) and lithium‐sensitive GSK3β—which enhance glutamate uptake and surface expression via direct phosphorylation and by inhibiting ubiquitin ligases like Nedd4-2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " This regulatory flexibility is critical as studies correlating EAAT4 expression levels with extrasynaptic glutamate transients indicate that even modest differences in expression can significantly affect neuroglial signaling in the cerebellum."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic analyses further implicate SLC1A6 in neuropsychiatric conditions; association studies have identified single nucleotide polymorphisms and haplotypes in the SLC1A6 region that correlate with an increased risk for schizophrenia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " While additional signaling molecules such as olfactory receptors have been shown to modulate functions in astrocytes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", the specialized expression and dual transport/channel properties of EAAT4 underscore its unique role in maintaining glutamate homeostasis and shaping synaptic as well as extrasynaptic transmission in cerebellar circuits.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hans Peter Koch, Ronald Lane Brown, Hans Peter Larsson "}, {"type": "b", "children": [{"type": "t", "text": "The glutamate-activated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0118-07.2007"}], "href": "https://doi.org/10.1523/JNEUROSCI.0118-07.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17360917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17360917"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Peter Kovermann, Jan-Philipp Machtens, David Ewers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.126557"}], "href": "https://doi.org/10.1074/jbc.M110.126557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20519505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20519505"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jan-Philipp Machtens, Peter Kovermann, Christoph Fahlke "}, {"type": "b", "children": [{"type": "t", "text": "Substrate-dependent gating of anion channels associated with excitatory amino acid transporter 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.207514"}], "href": "https://doi.org/10.1074/jbc.M110.207514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21572047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21572047"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jeyaganesh Rajamanickam, Monica Palmada, Florian Lang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EAAT4 phosphorylation at the SGK1 consensus site is required for transport modulation by the kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2007.04585.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2007.04585.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17442044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17442044"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Abeer Abousaab, Florian Lang "}, {"type": "b", "children": [{"type": "t", "text": "Up-Regulation of Excitatory Amino Acid Transporters EAAT3 and EAAT4 by Lithium Sensitive Glycogen Synthase Kinase GSK3ß."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000453179"}], "href": "https://doi.org/10.1159/000453179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27978527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27978527"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ming-Chi Tsai, Kohichi Tanaka, Linda Overstreet-Wadiche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal glutamate transporters regulate glial excitatory transmission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5232-11.2012"}], "href": "https://doi.org/10.1523/JNEUROSCI.5232-11.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22302796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22302796"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiangdong Deng, Hiroki Shibata, Naoko Takeuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30351"}], "href": "https://doi.org/10.1002/ajmg.b.30351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17221839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17221839"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Martina Von Wilmsdorff, Carolin Blaich, Mathias Zink, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Biol Psychiatry (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/15622975.2011.645877"}], "href": "https://doi.org/10.3109/15622975.2011.645877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22424243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22424243"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "TaeHo Cho, ChaeEun Lee, NaHye Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small-chain fatty acid activates astrocytic odorant receptor Olfr920."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.01.106"}], "href": "https://doi.org/10.1016/j.bbrc.2019.01.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30711253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30711253"}]}]}]}
Synonyms	EAAT4
Proteins	EAA4_HUMAN
NCBI Gene ID	6511
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC1A6 has 3,478 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for SLC1A6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC1A6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC1A6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC1A6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SLC1A6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SLC1A6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SLC1A6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC1A6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC1A6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC1A6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC1A6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SLC1A6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC1A6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC1A6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SLC1A6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC1A6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC1A6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SLC1A6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SLC1A6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC1A6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC1A6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SLC1A6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SLC1A6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC1A6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC1A6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC1A6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC1A6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SLC1A6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SLC1A6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SLC1A6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SLC1A6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SLC1A6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC1A6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SLC1A6 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SLC1A6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC1A6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC1A6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SLC1A6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SLC1A6 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SLC1A6 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC1A6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SLC1A6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.