SLC6A9 (Solute Carrier Family 6 Member 9)
Glycine Transporter 1 (GLYT1) - Key Regulator of Glycine Neurotransmission
Gene Information Card
| Symbol | SLC6A9 |
|---|---|
| Full Name | Solute Carrier Family 6 Member 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 6536 ncbi.nlm.nih.gov/gene/6536 |
| Ensembl ID | ENSG00000196517 |
| UniProt ID | P48067 |
| OMIM ID | 601019 |
| HGNC ID | 11052 |
| Aliases | GLYT1, GlyT-1, GLYT1 |
Description
SLC6A9 encodes the glycine transporter 1 (GLYT1), a member of the sodium- and chloride-dependent neurotransmitter transporter family. GLYT1 is primarily expressed in glial cells and regulates extracellular glycine concentrations in the central nervous system, thereby modulating NMDA receptor activity. It plays a critical role in inhibitory neurotransmission and is implicated in neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperekplexia (startle disease) | Loss-of-function mutations in SLC6A9 reduce glycine reuptake, leading to elevated synaptic glycine and altered glycinergic neurotransmission. | ClinVar, OMIM |
| Schizophrenia | Genetic variants in SLC6A9 are associated with altered NMDA receptor function via glycine modulation, contributing to glutamatergic dysfunction. | NCBI Gene, ClinVar |
| Glycine encephalopathy (nonketotic hyperglycinemia) | Impaired glycine transport due to SLC6A9 mutations can exacerbate glycine accumulation, though primary defects are in glycine cleavage system. | OMIM |
| Autism spectrum disorder | Rare variants in SLC6A9 have been reported in ASD cohorts, suggesting a role in synaptic glycine homeostasis. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Spinal cord | 8.3 | Medium |
| Retina | 6.1 | Medium |
| Liver | 0.9 | Low |
| Kidney | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| U-87 MG (glioblastoma) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.128G>A (p.Arg43His) | Missense | 0.001% | Reduced glycine uptake; associated with hyperekplexia |
| c.1015C>T (p.Arg339Trp) | Missense | 0.002% | Impaired transporter trafficking; linked to schizophrenia |
| c.1462delC (p.Leu488Trpfs*12) | Frameshift | Rare | Loss of function; reported in glycine encephalopathy |
| c.788A>G (p.Asn263Ser) | Missense | 0.0005% | Altered substrate affinity; autism spectrum disorder |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce glycine transport activity or cell surface expression, leading to elevated synaptic glycine and hyperekplexia.
Gain of Function (GOF)
Not well characterized; some variants may increase glycine reuptake, potentially contributing to hypofunction of NMDA receptors in schizophrenia.
Dominant Negative (DN)
Not reported for SLC6A9; mutations are typically recessive or act via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • neurotransmitter:sodium symporter activity (GO:0005328) | • symporter activity (GO:0015293) |
| • glycine:sodium symporter activity (GO:0015375) | • neurotransmitter transport (GO:0006836) |
| • glycine transport (GO:0015810) | • integral component of plasma membrane (GO:0005887) |
| • neuron projection (GO:0043005) | • chemical synaptic transmission (GO:0007268) |
Pathways
• Neurotransmitter uptake and metabolism (Reactome: R-HSA-112314)
• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)
• Glycine degradation (KEGG: map00260)
• NMDA receptor activation (KEGG: map04724)
Protein Summary
The SLC6A9 protein (GLYT1) is a 638-amino acid transmembrane transporter with 12 putative helical domains. It mediates the electrogenic symport of glycine with two sodium ions and one chloride ion. GLYT1 is predominantly expressed in glial cells of the brainstem, spinal cord, and retina, where it clears glycine from the synaptic cleft. This transporter is essential for maintaining low extracellular glycine levels, which is critical for proper NMDA receptor function and inhibitory glycinergic signaling. Alternative splicing generates multiple isoforms with distinct tissue distributions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC6A9 Knockout HEK293 Cell Line | EDJ-KQ2258 | Human | 6536 | Details Get a Quote |
| SLC6A9 Knockout A-549 Cell Line | EDJ-KQ23950 | Human | 6536 | Details Get a Quote |
| SLC6A9 Knockout HCT 116 Cell Line | EDJ-KQ23952 | Human | 6536 | Details Get a Quote |
| SLC6A9 Knockout HeLa Cell Line | EDJ-KQ23953 | Human | 6536 | Details Get a Quote |
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