SLC19A1: Folate Transporter and Disease Implications
Comprehensive genomic and functional overview of the SLC19A1 gene encoding the reduced folate carrier (RFC1)
Gene Information Card
| Symbol | SLC19A1 |
|---|---|
| Full Name | Solute Carrier Family 19 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 6573 ncbi.nlm.nih.gov/gene/6573 |
| Ensembl ID | ENSG00000160219 |
| UniProt ID | P41440 |
| OMIM ID | 600424 |
| HGNC ID | 10973 |
| Aliases | RFC1, CHMD, FOLT, IFC1, REFC, hRFC1 |
Description
SLC19A1 encodes the reduced folate carrier (RFC1), a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs such as methotrexate. It is essential for folate homeostasis and is expressed in various tissues. Mutations in SLC19A1 cause hereditary folate malabsorption and are associated with neural tube defects and methotrexate resistance in cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary folate malabsorption | Loss-of-function mutations impair intestinal folate absorption, leading to systemic folate deficiency | OMIM #229050 |
| Neural tube defects | Polymorphisms in SLC19A1 reduce folate transport during embryogenesis, increasing risk | NCBI Gene, PMID: 15689438 |
| Methotrexate resistance | Reduced expression or mutations in SLC19A1 decrease methotrexate uptake in cancer cells | COSMIC, PMID: 11861367 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 9.8 | Medium |
| Small intestine | 8.5 | Medium |
| Placenta | 15.2 | High |
| Bone marrow | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | High expression |
| K562 | 8.2 | Moderate expression |
| HepG2 | 11.0 | Moderate expression |
| MCF7 | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200C>T (p.Pro67Leu) | Missense | Rare | Loss of folate transport activity |
| c.588G>A (p.Trp196*) | Nonsense | Rare | Premature truncation, loss of function |
| c.80A>G (p.His27Arg) | Missense | Common (polymorphism) | Reduced methotrexate uptake |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations (e.g., p.Pro67Leu, p.Trp196*) impair folate transport, causing hereditary folate malabsorption.
Gain of Function (GOF)
Not reported for SLC19A1.
Dominant Negative (DN)
Not reported for SLC19A1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0008517 - folic acid transmembrane transporter activity | • GO:0015884 - folic acid transport |
| • GO:0015232 - reduced folate carrier activity | • GO:0015886 - methotrexate transport |
| • GO:0005887 - integral component of plasma membrane |
Pathways
• Folate metabolism (Reactome: R-HSA-196757)
• Methotrexate transport (Reactome: R-HSA-196783)
• Vitamin B9 (folate) transport (KEGG: hsa04978)
Protein Summary
The SLC19A1 protein (RFC1) is a 591-amino acid transmembrane transporter with 12 predicted membrane-spanning domains. It functions as a pH-dependent, high-affinity carrier for reduced folates (e.g., 5-methyltetrahydrofolate) and antifolates (e.g., methotrexate). The protein is localized to the plasma membrane and endosomes, and its activity is critical for cellular folate uptake. Post-translational modifications include glycosylation and phosphorylation, which modulate transport activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC19A1 Knockout HEK293 Cell Line | EDC07995 | Human | 6573 | Details Get a Quote |
| SLC19A1 Knockout A-549 Cell Line | EDJ-KQ27948 | Human | 6573 | Details Get a Quote |
| SLC19A1 Knockout HCT 116 Cell Line | EDC08116 | Human | 6573 | Details Get a Quote |
| SLC19A1 Knockout HeLa Cell Line | EDJ-KQ29209 | Human | 6573 | Details Get a Quote |
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