SLC25A22: Mitochondrial Glutamate Carrier and Epileptic Encephalopathy Gene
Solute Carrier Family 25 Member 22 – A key mitochondrial aspartate/glutamate carrier involved in early infantile epileptic encephalopathy and metabolic disorders.
Gene Information Card
| Symbol | SLC25A22 |
|---|---|
| Full Name | Solute carrier family 25 member 22 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 79751 ncbi.nlm.nih.gov/gene/79751 |
| Ensembl ID | ENSG00000177542 |
| UniProt ID | Q9H936 |
| OMIM ID | 609302 |
| HGNC ID | 19961 |
| Aliases | GC1, EIEE3, NET44 |
Description
SLC25A22 encodes the mitochondrial glutamate carrier 1 (GC1), a member of the SLC25 mitochondrial carrier family. It transports glutamate across the inner mitochondrial membrane in exchange for aspartate, playing a critical role in the malate-aspartate shuttle and urea cycle. Mutations in SLC25A22 cause early infantile epileptic encephalopathy 3 (EIEE3) and are associated with microcephaly, hypotonia, and developmental delay.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early infantile epileptic encephalopathy 3 (EIEE3) | Loss-of-function mutations impair mitochondrial glutamate/aspartate transport, disrupting neuronal energy metabolism and neurotransmitter cycling. | OMIM #609304; ClinVar; multiple case reports |
| Microcephaly, progressive, with seizures and developmental delay | Defective GC1 leads to reduced mitochondrial NADH shuttling and ATP production in developing brain. | OMIM #609304; PMID: 19752159 |
| Hyperammonemia (secondary) | Impaired urea cycle function due to deficient aspartate export from mitochondria. | Case reports; PMID: 19752159 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.2 | Medium |
| Kidney | 6.1 | Low |
| Heart | 4.3 | Low |
| Skeletal muscle | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | High expression |
| HepG2 (hepatocellular carcinoma) | 9.5 | Medium expression |
| HEK293 (embryonic kidney) | 7.2 | Medium expression |
| A549 (lung carcinoma) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.617C>T (p.Pro206Leu) | Missense | Rare | Loss of glutamate transport activity; associated with EIEE3 |
| c.238G>A (p.Gly80Arg) | Missense | Rare | Impaired mitochondrial targeting; severe phenotype |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; neonatal onset epilepsy |
| c.649_650delAG (p.Ser217fs) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported SLC25A22 mutations are loss-of-function, reducing or abolishing glutamate/aspartate exchange, leading to mitochondrial dysfunction and neuronal excitotoxicity.
Gain of Function (GOF)
No gain-of-function mutations have been described for SLC25A22.
Dominant Negative (DN)
No dominant-negative effects reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Malate-aspartate shuttle (Reactome: R-HSA-70263)
• Urea cycle (Reactome: R-HSA-70635)
• Mitochondrial glutamate/aspartate transport (KEGG: map00220)
Protein Summary
SLC25A22 (GC1) is a 323-amino acid mitochondrial inner membrane protein with six transmembrane helices. It functions as an antiporter exchanging cytosolic glutamate for mitochondrial aspartate, essential for the malate-aspartate shuttle and urea cycle. The protein is highly expressed in brain and liver. Defects cause early infantile epileptic encephalopathy 3 (EIEE3) due to impaired neuronal energy metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC25A22 Knockout HEK293 Cell Line | EDJ-KQ15309 | Human | 79751 | Details Get a Quote |
| SLC25A22 Knockout A-549 Cell Line | EDJ-KQ46009 | Human | 79751 | Details Get a Quote |
| SLC25A22 Knockout HCT 116 Cell Line | EDC07823 | Human | 79751 | Details Get a Quote |
| SLC25A22 Knockout HeLa Cell Line | EDJ-KQ46011 | Human | 79751 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
