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26 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SLC1A3
solute carrier family 1 member 3
Chromosome 5 · 5p13.2
NCBI Gene: 6507Ensembl: ENSG00000079215.15HGNC: HGNC:10941UniProt: A0A087WT87
162PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranehigh-affinity L-glutamate transmembrane transporter activityprotein bindingL-glutamate transmembrane transportepisodic ataxia type 6neurodegenerative diseaseosteoporosisFamilial paroxysmal ataxia
✦AI Summary

SLC1A3 encodes EAAT1 (excitatory amino acid transporter 1), a sodium-dependent, high-affinity glutamate transporter that plays crucial roles in maintaining glutamate homeostasis in the central nervous system 1. The protein mediates uptake of L-glutamate, L-aspartate, and D-aspartate through a symporter mechanism that co-transports amino acids with sodium ions while counter-transporting potassium 1. This transporter is essential for removing glutamate from synaptic clefts, preventing excitotoxicity that can damage neurons 1. SLC1A3 is primarily expressed in astrocytes and plays critical roles in various neurological conditions. Mutations in SLC1A3 cause episodic ataxia type 6 (EA6), a dominantly inherited disorder characterized by transient episodes of incoordination and truncal instability triggered by physical exertion or emotional stress 23. Beyond its classical transport function, SLC1A3 has emerged as a biomarker in multiple diseases, showing upregulation in diabetic nephropathy where it clusters in endothelial cells and correlates with renal function deterioration 4. The gene is also implicated in Alzheimer's disease pathogenesis, where microglial SLC1A3 expression increases glutamine metabolism and enhances amyloid-β clearance 56. Additionally, SLC1A3 contributes to glutamine uptake in colorectal cancer progression 7.

Sources cited
1
SLC1A3 encodes EAAT1, a sodium-dependent glutamate transporter that prevents excitotoxicity
PMID: 30851309
2
SLC1A3 mutations cause episodic ataxia type 6 with transient incoordination episodes
PMID: 39174244
3
EA6 is caused by heterozygous SLC1A3 mutations affecting glial amino acid transport
PMID: 29891059
4
SLC1A3 is upregulated in diabetic nephropathy and correlates with renal function deterioration
PMID: 36911691
5
Microglial SLC1A3 increases glutamine metabolism and enhances amyloid-β clearance in Alzheimer's disease
PMID: 39904338
6
SLC1A3 is a differentially expressed gene associated with AD pathology in middle temporal gyrus
PMID: 36544231
7
SLC1A3 contributes to glutamine uptake and metabolism in colorectal cancer progression
PMID: 39151722
Disease Associationsⓘ21
episodic ataxia type 6Open Targets
0.77Strong
neurodegenerative diseaseOpen Targets
0.49Moderate
osteoporosisOpen Targets
0.46Moderate
Familial paroxysmal ataxiaOpen Targets
0.41Moderate
Isaacs syndromeOpen Targets
0.37Weak
neuroinflammatory disorderOpen Targets
0.37Weak
bone diseaseOpen Targets
0.32Weak
placenta praeviaOpen Targets
0.30Weak
cutaneous melanomaOpen Targets
0.29Weak
biliary tract diseaseOpen Targets
0.27Weak
sialadenitisOpen Targets
0.26Weak
muscle crampOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
colorectal carcinomaOpen Targets
0.17Weak
hereditary episodic ataxiaOpen Targets
0.17Weak
alcohol drinkingOpen Targets
0.12Weak
multiple congenital anomalies/dysmorphic syndromeOpen Targets
0.12Weak
experimental autoimmune encephalomyelitisOpen Targets
0.08Suggestive
diverticular diseaseOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
Episodic ataxia 6UniProt
Pathogenic Variants2
NM_004172.5(SLC1A3):c.869C>G (p.Pro290Arg)Pathogenic
Episodic ataxia type 6
☆☆☆☆2013→ Residue 290
NM_004172.5(SLC1A3):c.556T>A (p.Cys186Ser)Pathogenic
Episodic ataxia type 6
☆☆☆☆2009→ Residue 186
View on ClinVar ↗
Related Genes
NESProtein interaction89%FABP7Protein interaction79%GFAPProtein interaction79%S100BProtein interaction79%ALDH1L1Protein interaction77%SLC38A3Protein interaction76%
Tissue Expression6 tissues
Brain
100%
Heart
13%
Ovary
6%
Lung
4%
Bone Marrow
4%
Liver
0%
Gene Interaction Network
Click a node to explore
SLC1A3NESFABP7GFAPS100BALDH1L1SLC38A3
PROTEIN STRUCTURE
Preparing viewer…
PDB5LM4 · 3.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.61LoF Tolerant
pLIⓘ
0.30Tolerant
Observed/Expected LoF0.41 [0.28–0.61]
RankingsWhere SLC1A3 stands among ~20K protein-coding genes
  • #2,778of 20,598
    Most Researched162 · top quartile
  • #4,264of 5,498
    Most Pathogenic Variants2
  • #4,198of 17,882
    Most Constrained (LOEUF)0.61 · top quartile
Genes detectedSLC1A3
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning.
PMID: 36911691
Front Immunol · 2023
1.00
2
Hemiplegic Migraine.
PMID: 37247170
Curr Neurol Neurosci Rep · 2023
0.90
3
NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer's disease progression.
PMID: 39904338
Immunity · 2025
0.80
4
The episodic ataxias.
PMID: 39174244
Handb Clin Neurol · 2024
0.70
5
Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.
PMID: 38462589
Brain · 2024
0.64