SLC40A1: Ferroportin-1 (FPN1) - Iron Export Transporter
Key regulator of systemic iron homeostasis; mutations cause hemochromatosis type 4 and ferroportin disease.
Gene Information Card
| Symbol | SLC40A1 |
|---|---|
| Full Name | Solute Carrier Family 40 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q32.2 |
| NCBI Gene ID | 30061 ncbi.nlm.nih.gov/gene/30061 |
| Ensembl ID | ENSG00000138449 |
| UniProt ID | Q9NP59 |
| OMIM ID | 604653 |
| HGNC ID | 10946 |
| Aliases | FPN1, IREG1, MTP1, SLC40A1, HFE4 |
Description
SLC40A1 encodes ferroportin-1 (FPN1), the only known cellular iron exporter in mammals. It is essential for iron efflux from duodenal enterocytes, macrophages, and hepatocytes into the plasma, where iron binds to transferrin. Ferroportin is regulated by hepcidin, which binds to FPN1 and induces its internalization and degradation, thereby controlling systemic iron levels. Mutations in SLC40A1 cause autosomal dominant hemochromatosis type 4 (ferroportin disease), characterized by iron overload in macrophages and elevated serum ferritin with low transferrin saturation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hemochromatosis type 4 (Ferroportin disease) | Loss-of-function mutations impair iron export from macrophages, leading to iron accumulation in reticuloendothelial cells; elevated ferritin, low transferrin saturation. | OMIM #606069; ClinVar; multiple case reports. |
| Hemochromatosis type 4 (gain-of-function variant) | Gain-of-function mutations (e.g., N144H) cause resistance to hepcidin, resulting in iron overload in hepatocytes and high transferrin saturation. | OMIM #606069; functional studies in cell lines. |
| Iron deficiency anemia (secondary) | Rare SLC40A1 variants may contribute to altered iron absorption and distribution. | Limited evidence; case reports. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Duodenum | 12.5 | High |
| Liver | 8.3 | Medium |
| Spleen | 7.1 | Medium |
| Bone marrow | 6.8 | Medium |
| Placenta | 5.2 | Medium |
| Lung | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 10.2 | High expression |
| THP-1 (monocyte/macrophage) | 8.5 | High expression |
| Caco-2 (intestinal epithelial) | 7.9 | High expression |
| K562 (erythroleukemia) | 3.4 | Moderate expression |
| HEK293 (embryonic kidney) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1402G>A (p.Asp468Asn) | Missense | <0.01% | Loss of function; impaired iron export |
| c.430A>C (p.Asn144His) | Missense | <0.01% | Gain of function; hepcidin resistance |
| c.539C>T (p.Thr180Ile) | Missense | <0.01% | Loss of function; reduced cell surface expression |
| c.744G>T (p.Gln248His) | Missense | <0.01% | Loss of function; defective iron export |
Mutation functional classification
Loss of Function (LOF)
Most SLC40A1 mutations are loss-of-function (e.g., D468N, T180I, Q248H), reducing iron export capacity and causing macrophage iron retention (ferroportin disease).
Gain of Function (GOF)
Rare gain-of-function mutations (e.g., N144H) render ferroportin resistant to hepcidin, leading to iron overload in hepatocytes and high transferrin saturation.
Dominant Negative (DN)
Some loss-of-function mutations may exert a dominant-negative effect by forming non-functional multimers, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005381 - iron ion transmembrane transporter activity | • GO:0006826 - iron ion transport |
| • GO:0016021 - integral component of membrane | • GO:0034755 - iron ion export across plasma membrane |
| • GO:0055072 - iron ion homeostasis |
Pathways
• Hepcidin-ferroportin signaling pathway
• Iron metabolism and absorption
• Transferrin cycle
Protein Summary
Ferroportin-1 (FPN1) is a 571-amino acid transmembrane protein with 12 predicted helices. It is the sole known iron exporter in vertebrates, localized to the basolateral membrane of duodenal enterocytes, macrophages, and hepatocytes. The protein binds hepcidin, a peptide hormone, leading to its internalization and degradation. Structural studies reveal a central cavity for iron translocation. Mutations disrupt iron export or hepcidin binding, causing iron overload disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC40A1 Knockout HEK293 Cell Line | EDC07994 | Human | 30061 | Details Get a Quote |
| SLC40A1 Knockout A-549 Cell Line | EDJ-KQ26194 | Human | 30061 | Details Get a Quote |
| SLC40A1 Knockout HCT 116 Cell Line | EDJ-KQ26195 | Human | 30061 | Details Get a Quote |
| SLC40A1 Knockout HeLa Cell Line | EDJ-KQ26196 | Human | 30061 | Details Get a Quote |
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