SLC15A4: Solute Carrier Family 15 Member 4
A proton-coupled amino acid transporter involved in immune signaling and lysosomal function
Gene Information Card
| Symbol | SLC15A4 |
|---|---|
| Full Name | Solute Carrier Family 15 Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.33 |
| NCBI Gene ID | 121260 ncbi.nlm.nih.gov/gene/121260 |
| Ensembl ID | ENSG00000139329 |
| UniProt ID | Q8N697 |
| OMIM ID | 615806 |
| HGNC ID | 10923 |
| Aliases | PHT1, hPHT1, PTR4 |
Description
SLC15A4 encodes a proton-coupled peptide/histidine transporter (PHT1) that mediates the uptake of small peptides and free histidine across lysosomal and plasma membranes. It is highly expressed in immune cells and plays a critical role in Toll-like receptor (TLR) signaling, particularly TLR7 and TLR9, by regulating endosomal amino acid availability and pH. Variants in SLC15A4 are associated with systemic lupus erythematosus (SLE) and other autoimmune conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic Lupus Erythematosus (SLE) | SLC15A4 variants alter endosomal pH and TLR7/9 signaling, promoting autoantibody production | Genome-wide association studies (GWAS) and functional studies (PMID: 24076602, 25639755) |
| Inflammatory Bowel Disease (IBD) | Dysregulated histidine transport affects intestinal immune homeostasis | GWAS meta-analysis (PMID: 26192919) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Whole blood | 8.2 | Low |
| Small intestine | 6.1 | Low |
| Colon | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression |
| Jurkat (T-cell) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1383201 (intronic) | SNV | 0.25 (East Asian) | Risk allele for SLE; alters splicing efficiency |
| rs3809346 (intronic) | SNV | 0.35 (European) | Associated with reduced SLC15A4 expression and SLE protection |
Mutation functional classification
Loss of Function (LOF)
Not reported in germline; knockdown in cell lines reduces TLR7/9 signaling
Gain of Function (GOF)
Not reported
Dominant Negative (DN)
Not reported
View complete mutation data：
Gene Ontology (GO)
| • GO:0005215 - transporter activity | • GO:0015297 - antiporter activity |
| • GO:0015171 - amino acid transmembrane transporter activity | • GO:0015293 - symporter activity |
| • GO:0005764 - lysosome | • GO:0016021 - integral component of membrane |
| • GO:0006857 - oligopeptide transport | • GO:0003333 - amino acid transmembrane transport |
| • GO:0042493 - response to drug |
Pathways
• Toll-like receptor signaling pathway (Reactome: R-HSA-168898)
• Transport of small molecules (Reactome: R-HSA-382551)
• Lysosomal amino acid transport (KEGG: hsa04142)
Protein Summary
SLC15A4 (PHT1) is a 12-transmembrane domain protein that functions as a proton-coupled symporter for di/tripeptides and histidine. It localizes primarily to lysosomal membranes and endosomes, where it regulates luminal pH and amino acid efflux. In immune cells, SLC15A4 is essential for optimal TLR7 and TLR9 activation, linking amino acid transport to innate immune responses. Its expression is enriched in lymphoid tissues and monocytes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC15A4 Knockout HEK293 Cell Line | EDJ-KQ7223 | Human | 121260 | Details Get a Quote |
| SLC15A4 Knockout A-549 Cell Line | EDJ-KQ33514 | Human | 121260 | Details Get a Quote |
| SLC15A4 Knockout HCT 116 Cell Line | EDC09911 | Human | 121260 | Details Get a Quote |
| SLC15A4 Knockout HeLa Cell Line | EDJ-KQ33517 | Human | 121260 | Details Get a Quote |
| SLC15A4 Overexpression THP-1 Stable Cell Line | EDJ-GQ119 | Human | 121260 | Details Get a Quote |
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