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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SLC1A2
solute carrier family 1 member 2
Chromosome 11 Β· 11p13
NCBI Gene: 6506Ensembl: ENSG00000110436.13HGNC: HGNC:10940UniProt: A0A2R8Y860
186PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
L-aspartate import across plasma membranecell surfaceprotein bindingL-glutamate transmembrane transportdevelopmental and epileptic encephalopathy, 41type 2 diabetes mellitusgenetic developmental and epileptic encephalopathyEpileptic encephalopathy
✦AI Summary

SLC1A2 encodes EAAT2 (excitatory amino acid transporter 2), the predominant glutamate transporter in the human brain that functions as a sodium-dependent, high-affinity transporter for L-glutamate, L-aspartate, and D-aspartate 1. EAAT2 operates as a symporter, transporting one amino acid molecule with 2-3 Na+ ions and one proton while counter-transporting one K+ ion, and mediates chloride flux to prevent charge accumulation 1. Beyond its classical neuronal role in glutamate clearance from synaptic clefts, EAAT2 functions in diverse cellular contexts including astrocytes where it regulates glutamate homeostasis and social memory 2, and in macrophages where it supports inflammatory responses through lysosomal amino acid efflux and mTORC1 activation 3. Disease-associated SLC1A2 variants cause developmental and epileptic encephalopathy with variable severity correlating with transporter dysfunction 14. EAAT2 dysfunction contributes to frontotemporal dementia pathogenesis through astroglial toxicity and synaptic degeneration 5. Additionally, cancer cells exploit EAAT2 disruption to hijack neurometabolic coupling and promote brain metastasis 6. The transporter's diverse roles make it a potential therapeutic target for neurological disorders, metabolic diseases, and cancer.

Sources cited
1
SLC1A2 encodes EAAT2 as the predominant glutamate transporter with sodium-dependent transport mechanism and disease-causing variants
PMID: 40174554
2
EAAT2 in astrocytes regulates glutamate homeostasis and social memory through adenosine signaling
PMID: 39366972
3
EAAT2 in macrophages supports inflammatory responses via lysosomal amino acid transport and mTORC1 activation
PMID: 38614854
4
SLC1A2 variants cause diverse neurological disorders including developmental and epileptic encephalopathy
PMID: 34797406
5
EAAT2 downregulation contributes to astroglial toxicity and synaptic degeneration in frontotemporal dementia
PMID: 36602862
6
Cancer cells target EAAT2 to disrupt neurometabolic coupling and promote brain metastasis
PMID: 38811525
Disease Associationsβ“˜21
developmental and epileptic encephalopathy, 41Open Targets
0.78Strong
type 2 diabetes mellitusOpen Targets
0.52Moderate
genetic developmental and epileptic encephalopathyOpen Targets
0.51Moderate
Epileptic encephalopathyOpen Targets
0.51Moderate
hypothyroidismOpen Targets
0.47Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
thyroid diseaseOpen Targets
0.43Moderate
myxedemaOpen Targets
0.38Weak
undetermined early-onset epileptic encephalopathyOpen Targets
0.37Weak
VitiligoOpen Targets
0.32Weak
familial hemolytic anemiaOpen Targets
0.31Weak
autoimmune thyroid diseaseOpen Targets
0.29Weak
cardiac arrestOpen Targets
0.28Weak
type 1 diabetes mellitusOpen Targets
0.28Weak
uterine fibroidOpen Targets
0.28Weak
multinodular goiterOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
Alzheimer diseaseOpen Targets
0.09Suggestive
AnxietyOpen Targets
0.09Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.09Suggestive
Developmental and epileptic encephalopathy 41UniProt
Pathogenic Variants10
NM_004171.4(SLC1A2):c.866C>G (p.Pro289Arg)Pathogenic
Developmental and epileptic encephalopathy, 41|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 289
NM_004171.4(SLC1A2):c.266T>C (p.Leu89Pro)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 89
NM_004171.4(SLC1A2):c.746del (p.Phe249fs)Likely pathogenic
Developmental and epileptic encephalopathy, 41
β˜…β˜†β˜†β˜†2023β†’ Residue 249
NM_004171.4(SLC1A2):c.1625A>G (p.His542Arg)Likely pathogenic
Developmental and epileptic encephalopathy, 41
β˜…β˜†β˜†β˜†2023β†’ Residue 542
NM_004171.4(SLC1A2):c.827T>G (p.Ile276Ser)Likely pathogenic
Developmental and epileptic encephalopathy, 41
β˜…β˜†β˜†β˜†2023β†’ Residue 276
NM_004171.4(SLC1A2):c.689T>C (p.Ile230Thr)Likely pathogenic
Developmental and epileptic encephalopathy, 41
β˜…β˜†β˜†β˜†2022β†’ Residue 230
NM_004171.4(SLC1A2):c.244G>A (p.Gly82Arg)Pathogenic
Developmental and epileptic encephalopathy, 41|not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 82
NM_004171.4(SLC1A2):c.872G>T (p.Gly291Val)Likely pathogenic
Developmental and epileptic encephalopathy, 41
β˜…β˜†β˜†β˜†2022β†’ Residue 291
NM_004171.4(SLC1A2):c.872G>A (p.Gly291Asp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†β†’ Residue 291
NM_004171.4(SLC1A2):c.244G>C (p.Gly82Arg)Pathogenic
Developmental and epileptic encephalopathy, 41
β˜†β˜†β˜†β˜†2013β†’ Residue 82
View on ClinVar β†—
Related Genes
SLC17A7Protein interaction100%SNCAProtein interaction99%SLC17A6Protein interaction99%SOD1Protein interaction99%GLULProtein interaction92%DLG4Protein interaction85%
Tissue Expression6 tissues
Brain
100%
Liver
6%
Heart
1%
Bone Marrow
0%
Lung
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
SLC1A2SLC17A7SNCASLC17A6SOD1GLULDLG4
PROTEIN STRUCTURE
Preparing viewer…
PDB7VR7 Β· 2.80 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.57Moderately Constrained
pLIβ“˜
0.84Intermediate
Observed/Expected LoF0.35 [0.22–0.57]
RankingsWhere SLC1A2 stands among ~20K protein-coding genes
  • #2,316of 20,598
    Most Researched186 Β· top quartile
  • #2,832of 5,498
    Most Pathogenic Variants10
  • #3,735of 17,882
    Most Constrained (LOEUF)0.57 Β· top quartile
Genes detectedSLC1A2
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Astrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice.
PMID: 39366972
Nat Commun Β· 2024
1.00
2
Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis.
PMID: 38811525
Nat Commun Β· 2024
0.90
3
Excitatory amino acid transporter supports inflammatory macrophage responses.
PMID: 38614854
Sci Bull (Beijing) Β· 2024
0.80
4
NF-ΞΊB-mediated cytokine secretion and glutamate metabolic reprogramming converge in breast cancer brain tropism.
PMID: 40639610
Cancer Lett Β· 2025
0.72
5
SLC1A2 rs3794087 variant and risk for essential tremor: a systematic review and meta-analysis.
PMID: 26313486
Pharmacogenet Genomics Β· 2015
0.70