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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC1A6
solute carrier family 1 member 6
Chromosome 19 · 19p13.12
NCBI Gene: 6511Ensembl: ENSG00000105143.14HGNC: HGNC:10944UniProt: B7Z7Q5
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneglutamate:sodium symporter activityneurotransmitter uptakeL-aspartate transmembrane transporter activityneurodegenerative diseasePhenotypic abnormalitybenign neoplasmosteoarthritis, hip
✦AI Summary

SLC1A6 encodes EAAT4, a sodium-dependent, high-affinity glutamate transporter that mediates the uptake of L-glutamate, L-aspartate, and D-aspartate by coupling the transport of one amino acid molecule with two or three Na+ ions and one proton, while counter-transporting one K+ ion 1. The transporter also mediates chloride flux uncoupled from amino acid transport, preventing negative charge accumulation 2. SLC1A6 plays a redundant role in rapidly removing glutamate from synaptic clefts, essential for terminating postsynaptic glutamate action. Clinically, SLC1A6 variants are associated with schizophrenia susceptibility; polymorphisms in SLC1A6 show significant association with schizophrenia in Japanese populations 3, and NRG1 risk genotypes correlate with decreased SLC1A6 expression in cerebellar regions 4. A genome-wide association study identified SLC1A6 variants (rs112501869) associated with normal hearing function at 0.25 kHz 5. In cancer, elevated SLC1A6 expression in bladder cancer promotes resistance to immunotherapy by suppressing CD8+ T cell effector function and reducing immune infiltration; SLC1A6 knockdown enhances immunotherapy efficacy 6. SLC1A6 has also been identified as an independent prognostic predictor in bladder cancer survival models 7. Genetic variations in SLC1A1 (not SLC1A6) associate with posttraumatic seizure risk following traumatic brain injury 8.

Sources cited
1
SLC1A6/EAAT4 mediates glutamate uptake through Na+/H+ co-transport and K+ counter-transport
PMID: 23506861
2
SLC1A6 transports glutamate and aspartates and mediates coupled chloride flux
PMID: 7791878
3
SLC1A6 polymorphisms show significant association with schizophrenia in Japanese populations
PMID: 17221839
4
NRG1 risk genotypes correlate with decreased SLC1A6 expression in cerebellum; antipsychotics suppress SLC1A6
PMID: 22424243
5
SLC1A6 variant rs112501869 associates with normal hearing function at 0.25 kHz
PMID: 40458558
6
SLC1A6 overexpression promotes immunotherapy resistance in bladder cancer; knockdown enhances CD8+ T cell function
PMID: 40481876
7
SLC1A6 is an independent prognostic predictor in bladder cancer survival models
PMID: 35462469
8
SLC1A1 (not SLC1A6) genetic variations associate with posttraumatic seizure risk
PMID: 27153812
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.35Weak
Phenotypic abnormalityOpen Targets
0.27Weak
benign neoplasmOpen Targets
0.12Weak
osteoarthritis, hipOpen Targets
0.12Weak
neoplasmOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.07Suggestive
hereditary neuropathy with liability to pressure palsiesOpen Targets
0.05Suggestive
frozen shoulderOpen Targets
0.04Suggestive
urinary bladder carcinomaOpen Targets
0.04Suggestive
Charcot-Marie-Tooth disease type 2B2Open Targets
0.04Suggestive
autosomal dominant slowed nerve conduction velocityOpen Targets
0.04Suggestive
infectionOpen Targets
0.03Suggestive
parkinsonism with polyneuropathyOpen Targets
0.03Suggestive
non-small cell lung carcinomaOpen Targets
0.03Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
bladder transitional cell carcinomaOpen Targets
0.02Suggestive
psoriasisOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
ependymomaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SPTBN2Protein interaction95%ARHGEF11Protein interaction91%KAT5Protein interaction91%RORAProtein interaction90%GRID2Protein interaction71%SLC1A1Protein interaction65%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
18%
Liver
2%
Ovary
2%
Lung
1%
Heart
0%
Gene Interaction Network
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SLC1A6SPTBN2ARHGEF11KAT5RORAGRID2SLC1A1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P48664
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.58Moderately Constrained
pLIⓘ
0.72Intermediate
Observed/Expected LoF0.37 [0.25–0.58]
RankingsWhere SLC1A6 stands among ~20K protein-coding genes
  • #13,737of 20,598
    Most Researched22
  • #3,822of 17,882
    Most Constrained (LOEUF)0.58 · top quartile
Genes detectedSLC1A6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Glutamate transporter SLC1A6 promotes resistance to immunotherapy in cancer.
PMID: 40481876
Cancer Immunol Immunother · 2025
1.00
2
Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment.
PMID: 22424243
World J Biol Psychiatry · 2013
0.90
3
Molecular mechanisms of schizophrenia.
PMID: 17982252
Cell Physiol Biochem · 2007
0.80
4
Construction of prognosis model of bladder cancer based on transcriptome.
PMID: 35462469
Zhejiang Da Xue Xue Bao Yi Xue Ban · 2022
0.70
5
Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia.
PMID: 17221839
Am J Med Genet B Neuropsychiatr Genet · 2007
0.60