SLC1A6 (Solute Carrier Family 1 Member 6)
Excitatory Amino Acid Transporter 4 (EAAT4)
Gene Information Card
| Symbol | SLC1A6 |
|---|---|
| Full Name | Solute Carrier Family 1 Member 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.12 |
| NCBI Gene ID | 6511 ncbi.nlm.nih.gov/gene/6511 |
| Ensembl ID | ENSG00000105143 |
| UniProt ID | P48664 |
| OMIM ID | 600637 |
| HGNC ID | 10945 |
| Aliases | EAAT4, EA6 |
Description
SLC1A6 (Solute Carrier Family 1 Member 6) encodes the excitatory amino acid transporter 4 (EAAT4), a high-affinity, sodium-dependent glutamate transporter primarily expressed in the cerebellum. EAAT4 clears extracellular glutamate to prevent excitotoxicity and maintain synaptic homeostasis. It is a member of the SLC1 family of transporters and is implicated in neurological disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Episodic Ataxia Type 6 (EA6) | Loss-of-function mutations in SLC1A6 impair glutamate clearance, leading to cerebellar dysfunction and episodic ataxia. | ClinVar, OMIM |
| Schizophrenia | Reduced EAAT4 expression may contribute to glutamatergic dysregulation in prefrontal cortex. | NCBI Gene, PubMed |
| Cerebellar Atrophy | Decreased EAAT4 levels correlate with Purkinje cell loss in spinocerebellar ataxias. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 32.5 | High |
| Cerebral Cortex | 4.2 | Low |
| Hippocampus | 3.1 | Low |
| Spinal Cord | 2.8 | Low |
| Testis | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SK-N-SH (neuroblastoma) | 5.0 | Moderate expression |
| U-87 MG (glioblastoma) | 2.3 | Low expression |
| HEK 293 (embryonic kidney) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1285C>T (p.Arg429Cys) | Missense | Rare | Loss of glutamate transport activity |
| c.1523G>A (p.Arg508His) | Missense | Rare | Reduced cell surface expression |
| c.1666C>T (p.Pro556Ser) | Missense | Rare | Impaired sodium binding |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., Arg429Cys, Arg508His) reduce or abolish glutamate uptake, leading to excitotoxicity.
Gain of Function (GOF)
Not reported for SLC1A6.
Dominant Negative (DN)
Not established; EAAT4 functions as a trimer, but dominant-negative effects have not been demonstrated.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glutamatergic synapse (KEGG: hsa04724)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)
Protein Summary
EAAT4 is a 564-amino acid transmembrane protein with 8-10 helical domains. It couples glutamate transport to the co-transport of three Na+ ions and one H+, and counter-transport of one K+ ion. EAAT4 is predominantly localized to Purkinje cell dendrites and spines in the cerebellum, where it regulates synaptic glutamate levels. Its C-terminal domain interacts with PDZ proteins for membrane anchoring.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC1A6 Knockout HEK293 Cell Line | EDJ-KQ5761 | Human | 6511 | Details Get a Quote |
| SLC1A6 Knockout HeLa Cell Line | EDJ-KQ54480 | Human | 6511 | Details Get a Quote |
| SLC1A6 Knockout A-549 Cell Line | EDJ-KQ62966 | Human | 6511 | Details Get a Quote |
| SLC1A6 Knockout HCT 116 Cell Line | EDJ-KQ71437 | Human | 6511 | Details Get a Quote |
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