SLC38A4: Solute Carrier Family 38 Member 4
A sodium-coupled neutral amino acid transporter involved in urea cycle and metabolic disorders
Gene Information Card
| Symbol | SLC38A4 |
|---|---|
| Full Name | Solute Carrier Family 38 Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.11 |
| NCBI Gene ID | 55089 ncbi.nlm.nih.gov/gene/55089 |
| Ensembl ID | ENSG00000139269 |
| UniProt ID | Q969I3 |
| OMIM ID | 608065 |
| HGNC ID | 10951 |
| Aliases | SNAT4, ATA3, NAT3, SLC38A4 |
Description
SLC38A4 encodes a sodium-coupled neutral amino acid transporter (SNAT4) that mediates the uptake of small neutral amino acids such as alanine, serine, and glutamine. It is highly expressed in the liver and plays a critical role in the urea cycle and gluconeogenesis by transporting glutamine. Mutations in SLC38A4 are associated with hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a disorder of the urea cycle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome | Impaired mitochondrial ornithine transport due to SLC38A4 dysfunction leads to urea cycle disruption | ClinVar, OMIM #608065 |
| Ornithine transcarbamylase deficiency-like phenotype | Defective glutamine transport reduces ammonia detoxification capacity | OMIM #238970 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 4.2 | Medium |
| Small intestine | 3.1 | Medium |
| Pancreas | 1.8 | Low |
| Skeletal muscle | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 8.7 | Hepatocyte model |
| HEK293 | 2.1 | Low endogenous expression |
| Caco-2 | 3.4 | Intestinal epithelial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118C>T (p.Arg40*) | Nonsense | <0.01% | Loss of function; truncation of transporter |
| c.535G>A (p.Gly179Arg) | Missense | <0.01% | Impaired amino acid transport activity |
| c.845T>C (p.Leu282Pro) | Missense | <0.01% | Reduced membrane localization |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg40*, p.Gly179Arg) disrupt transporter activity, leading to urea cycle dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported in SLC38A4.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Urea cycle (Reactome: R-HSA-70635)
• Transport of small neutral amino acids (Reactome: R-HSA-352230)
Protein Summary
SLC38A4 (SNAT4) is a 547-amino acid transmembrane protein with 11 predicted helices. It functions as a sodium-coupled symporter for neutral amino acids, particularly glutamine, alanine, and serine. The protein is localized to the plasma membrane and mitochondria, facilitating glutamine uptake for hepatic urea cycle and gluconeogenesis. Defects cause HHH syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC38A4 Knockout HEK293 Cell Line | EDJ-KQ15338 | Human | 55089 | Details Get a Quote |
| SLC38A4 Knockout HeLa Cell Line | EDJ-KQ56535 | Human | 55089 | Details Get a Quote |
| SLC38A4 Knockout A-549 Cell Line | EDJ-KQ65029 | Human | 55089 | Details Get a Quote |
| SLC38A4 Knockout HCT 116 Cell Line | EDJ-KQ73473 | Human | 55089 | Details Get a Quote |
