SLC46A1
Proton-coupled folate transporter (PCFT) gene
Gene Information Card
| Symbol | SLC46A1 |
|---|---|
| Full Name | solute carrier family 46 member 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 113235 ncbi.nlm.nih.gov/gene/113235 |
| Ensembl ID | ENSG00000176387 |
| UniProt ID | Q9NTI2 |
| OMIM ID | 611672 |
| HGNC ID | 30521 |
| Aliases | PCFT, HCP1, G21 |
Description
SLC46A1 (solute carrier family 46 member 1) encodes the proton-coupled folate transporter (PCFT), a transmembrane protein that mediates intestinal folate absorption in the acidic environment of the duodenum and jejunum. It also transports folates across the blood-brain barrier and into various tissues. Loss-of-function mutations cause hereditary folate malabsorption (HFM), an autosomal recessive disorder characterized by severe folate deficiency, megaloblastic anemia, and neurological deficits.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary folate malabsorption (HFM) | Loss-of-function mutations in SLC46A1 impair intestinal folate uptake, leading to systemic folate deficiency. | ClinVar, OMIM |
| Folate deficiency (non-syndromic) | Reduced PCFT activity may contribute to low serum folate levels in some individuals. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Duodenum | 12.5 | High |
| Jejunum | 10.8 | High |
| Liver | 3.2 | Medium |
| Kidney | 2.1 | Medium |
| Brain | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (intestinal) | 15.3 | High expression; used for folate transport studies |
| HepG2 (liver) | 4.1 | Moderate expression |
| HEK293 (embryonic kidney) | 2.8 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 0.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.194C>T (p.Pro65Leu) | Missense | Rare | Loss of function; associated with HFM |
| c.382G>A (p.Gly128Arg) | Missense | Rare | Loss of function; impaired folate transport |
| c.1088G>A (p.Arg363Gln) | Missense | Rare | Loss of function; reduced protein stability |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; no protein produced |
Mutation functional classification
Loss of Function (LOF)
Most SLC46A1 mutations cause loss of function, reducing or abolishing folate transport activity, leading to hereditary folate malabsorption.
Gain of Function (GOF)
No gain-of-function mutations have been reported in SLC46A1.
Dominant Negative (DN)
No dominant-negative effects have been described for SLC46A1 mutations.
View complete mutation data：
Gene Ontology (GO)
| • folic acid transmembrane transporter activity (GO:0008517) | • folic acid transport (GO:0015884) |
| • heme transmembrane transporter activity (GO:0015232) | • heme transport (GO:0015886) |
| • integral component of membrane (GO:0016021) |
Pathways
• Folate metabolism (Reactome: R-HSA-196757)
• Transport of vitamins and cofactors (Reactome: R-HSA-425410)
Protein Summary
The proton-coupled folate transporter (PCFT) is a 459-amino acid membrane protein with 12 transmembrane domains. It functions as a symporter, utilizing the proton gradient to drive folate uptake across the apical membrane of intestinal enterocytes and the choroid plexus. PCFT is essential for dietary folate absorption and for maintaining folate levels in the central nervous system.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC46A1 Knockout HEK293 Cell Line | EDJ-KQ7415 | Human | 113235 | Details Get a Quote |
| SLC46A1 Knockout A-549 Cell Line | EDJ-KQ31225 | Human | 113235 | Details Get a Quote |
| SLC46A1 Knockout HCT 116 Cell Line | EDJ-KQ32595 | Human | 113235 | Details Get a Quote |
| SLC46A1 Knockout HeLa Cell Line | EDJ-KQ32596 | Human | 113235 | Details Get a Quote |
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