Affinage

SLC40A1

Ferroportin · UniProt Q9NP59

Length
571 aa
Mass
62.5 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC40A1 (ferroportin/IREG1/MTP1/FPN1) is the mammalian basolateral iron export protein that mediates cellular iron efflux from enterocytes, macrophages, and other iron-handling cells, placing it at the central control point of systemic iron homeostasis (PMID:10882071, PMID:16054062). Direct reconstitution in Xenopus oocytes and human cell lines established it as a non-heme iron exporter localized to the basolateral membrane of polarized intestinal epithelium, with conditional knockout confirming its essential role in intestinal iron absorption and macrophage and hepatocyte iron release (PMID:10882071, PMID:16054062, PMID:15692071). In macrophages it drives iron recycling, with both transcript and protein induced by iron loading and erythrophagocytosis (PMID:12907459). SLC40A1 expression is controlled at multiple levels: transcriptionally by the heme-responsive Bach1/Nrf2 axis acting at a MARE/ARE promoter element, by zinc and cadmium through MTF-1 (consistent with ferroportin also exporting zinc), and by chromatin-modifying inputs including HDAC2-dependent H3K27 acetylation and H3K14 lactylation at its promoter; translationally through a 5' UTR IRE responsive to cellular iron; and post-transcriptionally via 3' UTR-targeting microRNAs (PMID:20179090, PMID:20688958, PMID:35942174, PMID:39822760, PMID:39747742). Inflammatory down-regulation in reticuloendothelial cells proceeds through TLR4 signaling (PMID:12161425). Protein stability is set by ubiquitin-mediated proteasomal degradation through E3 ligases LRSAM1 and UBA52 and by interaction with cathepsin B, loss of which causes iron accumulation, lipid peroxidation, and ferroptosis across glioma, neuronal, atherosclerotic, and renal contexts (PMID:38428828, PMID:39039049, PMID:39960586, PMID:38352945). Disease mutations partition into loss-of-function alleles that abolish iron export through impaired trafficking or transport-cycle gating (causing iron overload by haploinsufficiency) and gain-of-function alleles that retain export but resist hepcidin-mediated internalization and degradation, defining the SLC40A1-related hemochromatosis spectrum (PMID:15692071, PMID:19709084, PMID:21396368, PMID:30002125, PMID:30500107, PMID:39039793).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established the molecular identity of the long-sought duodenal basolateral iron exporter, defining where dietary iron leaves the enterocyte and how its message is iron-regulated.

    Evidence Xenopus oocyte iron efflux reconstitution, immunolocalization, and 5' UTR IRE functional analysis

    PMID:10882071

    Open questions at the time
    • Transport mechanism and stoichiometry not resolved
    • No structural model of the transporter
  2. 2002 High

    Linked ferroportin regulation to innate immune signaling, explaining how inflammation restricts iron availability in reticuloendothelial cells.

    Evidence LPS mouse model with TLR4 and TNF-R1a knockouts, Northern blotting

    PMID:12161425

    Open questions at the time
    • Downstream transcriptional effectors of TLR4 acting on the promoter not defined
    • Relationship to hepcidin-mediated control not addressed in this study
  3. 2003 Medium

    Distinguished systemic from local control, showing ferroportin responds to whole-body iron status rather than enterocyte iron content, unlike DMT1.

    Evidence Comparison of sla (mutant hephaestin) mice with iron-deficient wild-type mice, mRNA/protein analysis

    PMID:12730111

    Open questions at the time
    • The systemic signal itself not molecularly identified here
    • Single-lab genetic/dietary comparison
  4. 2003 High

    Defined ferroportin's role in macrophage iron recycling and showed erythrophagocytosis-driven induction is transcriptional and iron-dependent.

    Evidence Erythrophagocytosis assay in J774 macrophages with actinomycin D and iron chelation, reciprocal mRNA/protein analysis

    PMID:12907459

    Open questions at the time
    • Specific transcription factors not identified in this study
  5. 2004 Medium

    Probed an additional apical localization in enterocytes, raising the possibility ferroportin modulates apical iron uptake beyond basolateral export.

    Evidence Apical blocking-antibody iron uptake/efflux assays and membrane fractionation in IEC-6 and Caco-2 cells

    PMID:14684575

    Open questions at the time
    • Proposed DMT1 interaction not directly demonstrated
    • Apical role not confirmed in vivo or by other labs
  6. 2005 High

    Demonstrated genetic necessity in vivo across enterocytes, macrophages, and hepatocytes, and revealed a critical extraembryonic role from the embryonic lethality of global knockouts.

    Evidence Conditional and global Cre-lox knockout mice with tissue-selective inactivation and histological iron quantification

    PMID:16054062

    Open questions at the time
    • Does not resolve transport mechanism
    • Cell-autonomous versus systemic contributions to each phenotype not fully separated
  7. 2005 High

    Separated the two molecular categories of disease alleles, showing some mutants abolish export (haploinsufficiency) while others retain export but are hepcidin-resistant.

    Evidence In vitro iron export assay in human cells with site-directed mutagenesis of multiple disease variants

    PMID:15692071

    Open questions at the time
    • Hepcidin-resistance mechanism for specific variants not directly assayed here
    • Structural basis of loss-of-function not defined
  8. 2005 Medium

    Extended ferroportin function to neuronal iron homeostasis, correlating its expression with cellular iron content and efflux.

    Evidence Western blot, immunocytochemistry, and iron efflux assays in SH-SY5Y and hippocampal neurons

    PMID:15667655

    Open questions at the time
    • Correlative rather than causal in neurons
    • Regulatory pathway in neurons not defined
  9. 2009 Medium

    Confirmed the gain-of-function hepcidin-resistance disease mechanism at the cellular level for a specific variant reaching the membrane normally.

    Evidence In vitro iron export and hepcidin inhibition assays with membrane localization for Y501C

    PMID:19709084

    Open questions at the time
    • Structural basis of hepcidin resistance not resolved
    • Single-lab cellular assay
  10. 2010 High

    Resolved dual heme-responsive transcriptional control, with Bach1 repressing and Nrf2 activating via a MARE/ARE element, while heme-derived iron acts through the IRE on translation.

    Evidence Promoter reporter mutagenesis, siRNA knockdown, and overexpression in macrophages

    PMID:20179090

    Open questions at the time
    • Quantitative integration of transcriptional and translational control not defined
  11. 2010 High

    Identified metal-responsive transcriptional control via MTF-1 and showed ferroportin can export zinc to protect against zinc toxicity, broadening its substrate scope.

    Evidence MTF-1 siRNA, promoter reporter with site mutations, nuclear translocation, and zinc export assay

    PMID:20688958

    Open questions at the time
    • Physiological relevance of zinc transport in vivo not established
    • Selectivity determinants between iron and zinc not defined
  12. 2011 High

    Mechanistically dissected two mutation classes — trafficking-defective loss-of-function and hepcidin-binding-defective gain-of-function — and mapped a hepcidin-interacting peptide region.

    Evidence In vitro iron export, membrane trafficking imaging, and synthetic peptide hepcidin inhibition assays in 293T cells for W158C and H507R

    PMID:21396368

    Open questions at the time
    • Full hepcidin-binding interface not structurally defined
  13. 2017 Medium

    Showed Nrf2 can also act as a transcriptional repressor of SLC40A1 in cancer, linking ferroportin suppression to chemoresistance.

    Evidence ChIP, dual-luciferase reporter, Nrf2 knockdown/overexpression, and SLC40A1 rescue in ovarian cancer cells

    PMID:29212168

    Open questions at the time
    • Apparent context-dependent opposite Nrf2 effects versus macrophage data not reconciled
    • Single-lab study
  14. 2018 Medium

    Defined a third mutation category — gating residues that impair the transport conformational cycle without mislocalization — refining the structural basis of loss-of-function.

    Evidence In vitro iron export, localization imaging, and 3D structural modeling for R178Q with multi-family clinical correlation

    PMID:30002125

    Open questions at the time
    • Conformational cycle inferred from modeling, not experimental structures
    • Single-lab functional work
  15. 2018 Medium

    Added a hepcidin-resistant gain-of-function allele causing hemochromatosis in an additional population.

    Evidence Transfection, hepcidin treatment, localization imaging, and Western blot for Y333H in 293T cells

    PMID:30500107

    Open questions at the time
    • Structural basis of resistance not resolved
    • Single-lab study
  16. 2022 Medium

    Established microRNA control of ferroportin, with miR-147a and miR-4735-3p directly targeting the 3' UTR to suppress iron export and drive ferroptosis in tumor cells.

    Evidence 3' UTR luciferase reporters, miRNA mimic/inhibitor, siRNA, and SLC40A1 overexpression rescue with iron and lipid peroxidation assays in glioblastoma and ccRCC

    PMID:35646516 PMID:35942174

    Open questions at the time
    • Physiological versus tumor-specific relevance not separated
    • Single-lab per study
  17. 2023 Medium

    Identified protein-degradation and binding partners controlling ferroportin stability — UBA52 ubiquitination in injured neurons and cathepsin B binding in atherosclerotic macrophages — linking destabilization to iron accumulation and ferroptosis.

    Evidence Co-IP, ubiquitination assays, knockdown/inhibition, and competitive binding (hydralazine) with ferroptosis readouts

    PMID:38352945 PMID:39960586

    Open questions at the time
    • Reciprocal validation and direct binding interfaces not fully defined
    • Single-lab per study
  18. 2023 Medium

    Demonstrated cell-type-specific, time-dependent consequences of ferroportin loss in brain endothelium during ischemic stroke, protective acutely but impairing later recovery.

    Evidence VE-cadherin-Cre conditional Fpn1 knockout mice in MCAO model with behavioral, infarct, and ferroptosis/apoptosis readouts

    PMID:36841833

    Open questions at the time
    • Molecular trigger of late-phase iron deficiency effects not defined
    • Single-lab study
  19. 2024 Medium

    Connected additional regulators of ferroportin protein stability — STING-dependent ubiquitination and the LRSAM1 E3 ligase under REST/Erianin control — to ferroptosis in renal epithelium and resistant glioma stem cells.

    Evidence Ubiquitination and proteasomal degradation assays, Co-IP, ChIP, and FPN1 disruption rescue

    PMID:38428828 PMID:39039049

    Open questions at the time
    • Direct versus indirect role of STING in ubiquitination not fully resolved
    • Single-lab per study
  20. 2024 Medium

    Resolved graded biophysical effects of further disease variants, separating local instabilities from impaired rigid-body movements of the transport cycle and partial hepcidin desensitization.

    Evidence In vitro iron export and hepcidin sensitivity assays with structural modeling and clinical correlation for R40Q, S47F, and A350V

    PMID:39039793

    Open questions at the time
    • Mechanistic claims rest on modeling rather than experimental structures
    • Single-lab work
  21. 2025 Medium

    Expanded chromatin-level control of SLC40A1 transcription, implicating H3K14 lactylation, HDAC2-dependent H3K27 acetylation, and oligodendrocyte iron homeostasis in tissue injury and behavior.

    Evidence Cut&Tag, ChIP, DNA pulldown, glycolysis/HDAC2 manipulation, and oligodendrocyte-specific conditional knockout with behavioral and signaling readouts

    PMID:39747742 PMID:39822760 PMID:40609802

    Open questions at the time
    • Direct factors writing/reading these marks at the promoter not fully defined
    • Single-lab per study

Open questions

Synthesis pass · forward-looking unresolved questions
  • An experimentally determined structure of human ferroportin in distinct transport-cycle conformations and bound to hepcidin would unify the scattered mutation classes into a single mechanistic framework.
  • No experimental structure in the timeline
  • Transport stoichiometry and ion coupling unresolved
  • Hepcidin-binding interface defined only by peptide and modeling

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-5357801 Programmed Cell Death 6 R-HSA-382551 Transport of small molecules 3 R-HSA-1430728 Metabolism 2
Partners
CTSBHAMPLRSAM1UBA52

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 IREG1 (SLC40A1) is localized to the basolateral membrane of polarized intestinal epithelial cells and stimulates iron efflux when expressed in Xenopus oocytes, establishing it as the duodenal basolateral iron export protein. Its mRNA contains a functional iron-responsive element (IRE) in the 5' UTR, and expression is increased under conditions of elevated iron absorption. Xenopus oocyte iron efflux assay, cDNA isolation, immunolocalization, IRE functional analysis Molecular cell High 10882071
2005 Embryonic and conditional knockout of murine ferroportin (Fpn/SLC40A1) demonstrates that ferroportin is essential for iron export from enterocytes, macrophages, and hepatocytes. Embryonic lethality of global knockouts is rescued by selective inactivation in the embryo proper, indicating a critical role in extraembryonic visceral endoderm. Intestine-specific inactivation confirms ferroportin is critical for intestinal iron absorption. Conditional and global gene knockout (Cre-lox), tissue-selective inactivation, histological iron quantification Cell metabolism High 16054062
2005 Human FPN (SLC40A1) expressed in a human cell line causes iron deficiency via a ~3-fold increase in iron export. Loss-of-function mutations A77D, V162del, and G490D abolish iron export without physically impeding wild-type FPN, indicating haploinsufficiency as the disease mechanism. Variants Y64N, N144D, N144H, Q248H, and C326Y retain iron export function in vitro, suggesting resistance to hepcidin-mediated inhibition rather than loss of export activity. In vitro iron export assay in human cell lines, site-directed mutagenesis, cellular iron quantification Blood High 15692071
2002 MTP1 (SLC40A1) expression in reticuloendothelial system (RES) cells of spleen, liver, and bone marrow is down-regulated by lipopolysaccharide-induced acute inflammation. This down-regulation requires signaling through TLR4, as mice lacking TLR4 do not show altered MTP1 expression after LPS treatment. TNF-receptor 1a is not required for this LPS effect. LPS mouse model, Northern blotting, TLR4 and TNF-R1a knockout mice The Journal of biological chemistry High 12161425
2003 FPN1 (SLC40A1) mRNA and protein levels in J774 macrophages increase with iron loading and after erythrophagocytosis (up to 8-fold at 4 hours). Induction after erythrophagocytosis results from erythrocyte-derived iron (blocked by iron chelation) and involves transcriptional control (blocked by actinomycin D). This establishes FPN1's role in macrophage iron recycling. Northern blotting, Western blotting, actinomycin D transcription block, iron chelation, erythrophagocytosis assay Blood High 12907459
2010 FPN1 transcription is inhibited by Bach1 and activated by Nrf2 (Nuclear Factor Erythroid 2-like) via a MARE/ARE element at position -7007 of the FPN1 promoter in macrophages. The protoporphyrin ring of heme is sufficient to increase FPN1 transcriptional activity, while iron released from heme controls FPN1 translation through the IRE in the 5' UTR. siRNA knockdown, overexpression, reporter construct with truncations and MARE/ARE mutations, luciferase assay Haematologica High 20179090
2010 FPN1 transcription is induced by zinc and cadmium through Metal Transcription Factor-1 (MTF-1), which translocates to the nucleus and binds to two MTF-1 binding sites in the mouse FPN1 promoter. MTF-1 silencing reduces FPN1 transcription in response to zinc but not iron. Fpn can transport zinc and protect zinc-sensitive cells from zinc toxicity. MTF-1 siRNA knockdown, promoter reporter assay with MTF-1 site mutations, nuclear translocation assay, zinc export functional assay Blood High 20688958
2003 Hephaestin and Ireg1 (SLC40A1) expression respond to systemic rather than local signals of iron status in intestinal enterocytes, in contrast to DMT1 which is regulated by local enterocyte iron levels. This was demonstrated by comparing sla mice (with mutant hephaestin) to iron-deficient wild-type mice. Genetic comparison (sla mouse model vs. iron-deficient diet), mRNA and protein expression analysis Blood Medium 12730111
2004 Ferroportin (SLC40A1) is present at the apical membrane (brush border) of enterocytes in addition to the basolateral membrane. A blocking antibody to ferroportin applied to the apical membrane significantly reduced Fe(II) uptake by 40-50% but had no effect on iron release, suggesting ferroportin modulates apical iron uptake possibly through interaction with DMT1. Blocking antibody assay, iron uptake/efflux assays in IEC-6 and Caco-2 cells, microvillus membrane fractionation, immunofluorescence Gut Medium 14684575
2009 The SLC40A1 p.Y501C variant reaches the plasma membrane normally and retains full iron export ability, but is resistant to hepcidin-mediated inhibition in cultured cells, confirming that certain ferroportin mutations confer hepcidin resistance (gain-of-function) leading to iron overload resembling HFE hemochromatosis. In vitro functional assay in cultured cells, hepcidin inhibition assay, plasma membrane localization by immunofluorescence British journal of haematology Medium 19709084
2011 SLC40A1 p.W158C impairs intracellular trafficking of ferroportin to the plasma membrane, resulting in reduced iron export (loss-of-function). SLC40A1 p.H507R localizes normally to the plasma membrane but does not bind hepcidin in vitro and is resistant to hepcidin-mediated inactivation. A synthetic peptide from amino acids 500-518 of wild-type ferroportin decreased hepcidin inhibitory activity in cells, while the H507R peptide had no effect. In vitro iron export assay in 293T cells, immunofluorescence for membrane localization, synthetic peptide hepcidin inhibition assay Gastroenterology High 21396368
2018 SLC40A1 p.R178Q reduces FPN1 iron export ability without causing protein mislocalization, representing a new category of loss-of-function mutation affecting gating residues required for conformational changes during iron transport. Structural modeling of human FPN1 indicates R178 is part of an interaction network modulating the outward-facing conformation. In vitro iron export assay, protein localization by immunofluorescence, 3D structural comparative modeling, clinical and histological data from 22 patients across 6 families Haematologica Medium 30002125
2018 SLC40A1 p.Y333H mutant ferroportin is resistant to hepcidin-mediated internalization and degradation in 293T cells, and is associated with gain-of-function iron export activity (hepcidin resistance phenotype), establishing this mutation as a cause of haemochromatosis in China. Transfection in 293T cells, hepcidin treatment assay, immunofluorescence for cellular localization, Western blotting for FPN1 and ferritin Liver international Medium 30500107
2017 Nrf2 transcriptionally suppresses SLC40A1 expression in ovarian cancer cells. ChIP and dual-luciferase reporter assay confirmed Nrf2 binds SLC40A1 promoter to inhibit its transcription. Knockdown of Nrf2 increases SLC40A1 expression; overexpression of Nrf2 decreases it. SLC40A1 overexpression reverses Nrf2-induced cisplatin resistance. ChIP assay, dual-luciferase reporter assay, Nrf2 knockdown and overexpression, SLC40A1 overexpression rescue experiment Oncotarget Medium 29212168
2022 miR-147a directly binds the 3'-UTR of SLC40A1 and inhibits SLC40A1-mediated iron export, thereby facilitating iron overload, lipid peroxidation, and ferroptosis in glioblastoma cells. 3'-UTR luciferase reporter assay, miR-147a mimic/inhibitor transfection, SLC40A1 siRNA knockdown, iron and lipid peroxidation measurement Analytical cellular pathology (Amsterdam) Medium 35942174
2022 miR-4735-3p directly targets SLC40A1; its overexpression suppresses SLC40A1-mediated iron export, leading to iron overload and ferroptosis in clear cell renal cell carcinoma cells. SLC40A1 overexpression rescued iron overload and ferroptosis in miR-4735-3p mimic-treated cells. Mechanistic study identifying SLC40A1 as direct miR-4735-3p target, adenoviral SLC40A1 overexpression rescue, lipid peroxidation and iron assays Analytical cellular pathology (Amsterdam) Medium 35646516
2024 STING inhibition stabilizes FPN1 protein by decreasing ubiquitin-mediated proteasomal degradation of FPN1 in renal tubular epithelial cells, thereby alleviating ferroptosis. Disruption of FPN1 on the basis of STING inhibition abolished the ferroptosis improvements, confirming FPN1 stabilization as the mechanism. STING inhibition/deficiency model, ubiquitination assay, proteasomal degradation assay, FPN1 disruption rescue experiment Biochemical pharmacology Medium 38428828
2024 LRSAM1 ubiquitinates and degrades SLC40A1, reducing iron export and inducing ferroptosis in TMZ-resistant glioma stem cells. Erianin suppresses REST transcriptional repression to upregulate LRSAM1, which then ubiquitinates SLC40A1. Co-IP assays confirmed the LRSAM1–SLC40A1 interaction. Co-immunoprecipitation, ubiquitination assay, protein stability assessment, ChIP assay, luciferase reporter assay Cell death & disease Medium 39039049
2023 Cathepsin B (CTSB) binds FPN and negatively regulates FPN protein levels by promoting its degradation, causing iron accumulation and ferroptosis in macrophages during atherosclerosis. This was confirmed by co-immunoprecipitation and knockdown/inhibition of CTSB. Co-immunoprecipitation, CTSB knockdown and pharmacological inhibition, iron and ferroptosis assays, single-cell transcriptomics Molecular and cellular biochemistry Medium 39960586
2023 UBA52 ubiquitinates and promotes degradation of ferroportin (FPN/SLC40A1) in neurons following peripheral nerve injury, causing iron accumulation and ferroptosis. Hydralazine binds to UBA52 and competitively inhibits FPN ubiquitination, thereby restoring FPN levels and suppressing neuronal ferroptosis. In vitro and in vivo ubiquitination assay, Co-IP, competitive binding assay with hydralazine and UBA52, neuronal ferroptosis quantification Journal of pharmaceutical analysis Medium 38352945
2025 H3K14 lactylation (H3K14la) is enriched at the SLC40A1 promoter in pulmonary endothelial cells during sepsis, and this epigenetic mark drives transcriptional regulation of SLC40A1, contributing to EC ferroptosis and lung injury. Suppressing glycolysis reduced H3K14la and EC activation. Cut&Tag analysis of H3K14la at SLC40A1 promoter, lactylome and proteome integration, glycolysis inhibition MedComm Medium 39822760
2025 HDAC2 transcriptionally inhibits FPN expression by reducing histone H3K27 acetylation at the FPN promoter region during hypoxia/reoxygenation injury. Dexmedetomidine inhibits HDAC2, restoring H3K27Ac at the FPN promoter, upregulating FPN, and inhibiting cardiomyocyte ferroptosis. DNA pulldown assay, ChIP assay for HDAC2 binding at FPN promoter and H3K27Ac levels, HDAC2 overexpression/knockdown, FPN knockdown rescue Cardiovascular drugs and therapy Medium 39747742
2024 SLC40A1 p.Arg40Gln and p.Ser47Phe substitutions partially reduce FPN1 iron export and partially reduce hepcidin sensitivity. p.Ala350Val more profoundly reduces iron egress and weakens FPN1/hepcidin interaction. Structural analysis indicates the latter prevents rigid-body movements essential to the iron transport cycle, while the first two cause local instabilities. In vitro iron export assay in cultured cells, hepcidin sensitivity assay, structural modeling, clinical phenotype correlation in 12 affected individuals HGG advances Medium 39039793
2005 IREG1 (SLC40A1) expression in neuroblastoma (SH-SY5Y) and hippocampal neurons increases in response to progressive iron accumulation, correlates directly with cellular iron content, and its increased expression correlates with increased iron efflux from cells, establishing its role in neuronal iron homeostasis. Western blotting, immunocytochemistry, iron efflux assay, correlation analysis BMC neuroscience Medium 15667655
2019 Iron dyshomeostasis induces binding of APP to BACE1, promoting amyloid formation, and decreases the functional APP/Fpn1 complex in microglia, impairing iron export in an iron-overload model. FeCl3 treatment of microglia, protein expression analysis, co-localization and interaction analysis of APP and Fpn1 Cell transplantation Low 30776900
2023 Conditional deletion of Fpn1 in mouse brain microvascular endothelial cells (Cdh5-Cre) decreased brain iron levels, attenuated oxidative stress, inflammation, ferroptosis, and apoptosis in the acute phase of ischemic stroke, alleviating neurological impairment. However, Fpn1 knockout in ECs delayed neurological recovery in the later stages, associated with iron deficiency-induced inhibition of neuronal development and enhanced glial proliferation. VE-cadherin-Cre conditional Fpn1 knockout mice, MCAO stroke model, behavioral testing, cerebral infarct measurement, ferroptosis/apoptosis markers Cell death & disease Medium 36841833
2025 Conditional knockout of Fpn1 in oligodendrocytes (Fpn1Olig2-cKO) caused iron accumulation, elevated ROS, activation of MAPK/ERK, AKT/JNK, and NF-κB pathways, and upregulation of hepcidin in the prefrontal cortex and hippocampus, leading to myelin defects, disrupted synaptic formation, and depression-like behaviors in mice. Oligodendrocyte-specific Fpn1 conditional knockout (Cre-lox), behavioral testing, Western blotting for signaling pathways, FPN1 silencing in human MO3.13 cells, ICG-001 pharmacological pathway dissection Free radical biology & medicine Medium 40609802

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Molecular cell 1129 10882071
2005 The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell metabolism 991 16054062
2013 Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. Journal of neurochemistry 317 23506423
2010 Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position -7007 of the FPN1 promoter. Haematologica 234 20179090
2003 Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood 189 12907459
2005 In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood 166 15692071
2002 Regulation of reticuloendothelial iron transporter MTP1 (Slc11a3) by inflammation. The Journal of biological chemistry 163 12161425
2003 A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block phenomenon of iron absorption. Gut 142 12584213
2022 Activation of NRF2/FPN1 pathway attenuates myocardial ischemia-reperfusion injury in diabetic rats by regulating iron homeostasis and ferroptosis. Cell stress & chaperones 127 35124772
2010 Induction of FPN1 transcription by MTF-1 reveals a role for ferroportin in transition metal efflux. Blood 112 20688958
2001 Zinc regulates the function and expression of the iron transporters DMT1 and IREG1 in human intestinal Caco-2 cells. FEBS letters 101 11684086
2008 MTP1-dependent Zn sequestration into shoot vacuoles suggests dual roles in Zn tolerance and accumulation in Zn-hyperaccumulating plants. The Plant journal : for cell and molecular biology 100 19054361
2003 Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency. Blood 98 12730111
2006 Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infection and immunity 93 16428741
2021 SLC40A1 Mediates Ferroptosis and Cognitive Dysfunction in Type 1 Diabetes. Neuroscience 90 33727075
2012 The dopamine metabolite aminochrome inhibits mitochondrial complex I and modifies the expression of iron transporters DMT1 and FPN1. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 72 22302610
2017 Nrf2 induces cisplatin resistance via suppressing the iron export related gene SLC40A1 in ovarian cancer cells. Oncotarget 69 29212168
2005 Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum. Vaccine 67 15837211
2002 Iron increases expression of iron-export protein MTP1 in lung cells. American journal of physiology. Lung cellular and molecular physiology 67 12376346
2003 The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1). Pflugers Archiv : European journal of physiology 63 12836025
2005 Iron homeostasis in neuronal cells: a role for IREG1. BMC neuroscience 59 15667655
2023 Cigarette tar mediates macrophage ferroptosis in atherosclerosis through the hepcidin/FPN/SLC7A11 signaling pathway. Free radical biology & medicine 57 36933812
2003 Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin. Journal of molecular medicine (Berlin, Germany) 57 14618243
2003 DMT1 and FPN1 expression during infancy: developmental regulation of iron absorption. American journal of physiology. Gastrointestinal and liver physiology 55 12958019
2011 Identification of mutations in SLC40A1 that affect ferroportin function and phenotype of human ferroportin iron overload. Gastroenterology 54 21396368
2024 SLC40A1 in iron metabolism, ferroptosis, and disease: A review. WIREs mechanisms of disease 50 38508867
2022 Edaravone Ameliorates Cerebral Ischemia-Reperfusion Injury by Downregulating Ferroptosis via the Nrf2/FPN Pathway in Rats. Biological & pharmaceutical bulletin 48 36047195
2014 Two metal-tolerance proteins, MTP1 and MTP4, are involved in Zn homeostasis and Cd sequestration in cucumber cells. Journal of experimental botany 47 25422498
2022 MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma. Analytical cellular pathology (Amsterdam) 46 35942174
2002 Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells. The Journal of nutrition 45 11925462
2020 Transmembrane protein western blotting: Impact of sample preparation on detection of SLC11A2 (DMT1) and SLC40A1 (ferroportin). PloS one 43 32645092
2003 Effect of vaccination with a recombinant fusion protein encoding an astacinlike metalloprotease (MTP-1) secreted by host-stimulated Ancylostoma caninum third-stage infective larvae. The Journal of parasitology 42 14533704
2022 MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1. Analytical cellular pathology (Amsterdam) 36 35646516
2004 Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes. Gut 36 14684575
2009 A novel missense mutation in SLC40A1 results in resistance to hepcidin and confirms the existence of two ferroportin-associated iron overload diseases. British journal of haematology 32 19709084
2025 H3K14la drives endothelial dysfunction in sepsis-induced ARDS by promoting SLC40A1/transferrin-mediated ferroptosis. MedComm 31 39822760
2023 Cdh5-mediated Fpn1 deletion exerts neuroprotective effects during the acute phase and inhibitory effects during the recovery phase of ischemic stroke. Cell death & disease 30 36841833
2015 Imaging malignant melanoma with (18)F-5-FPN. European journal of nuclear medicine and molecular imaging 30 26260649
2005 A Japanese family with ferroportin disease caused by a novel mutation of SLC40A1 gene: hyperferritinemia associated with a relatively low transferrin saturation of iron. Internal medicine (Tokyo, Japan) 30 16258219
2024 STING deficiency alleviates ferroptosis through FPN1 stabilization in diabetic kidney disease. Biochemical pharmacology 29 38428828
2007 Novel mutations of the ferroportin gene (SLC40A1): analysis of 56 consecutive patients with unexplained iron overload. Clinical genetics 29 18177470
2024 Erianin induces ferroptosis in GSCs via REST/LRSAM1 mediated SLC40A1 ubiquitination to overcome TMZ resistance. Cell death & disease 28 39039049
2019 Iron Dyshomeostasis Induces Binding of APP to BACE1 for Amyloid Pathology, and Impairs APP/Fpn1 Complex in Microglia: Implication in Pathogenesis of Cerebral Microbleeds. Cell transplantation 27 30776900
2013 Silencing the Menkes copper-transporting ATPase (Atp7a) gene in rat intestinal epithelial (IEC-6) cells increases iron flux via transcriptional induction of ferroportin 1 (Fpn1). The Journal of nutrition 27 24174620
2020 miR-194-5p inhibits SLC40A1 expression to induce cisplatin resistance in ovarian cancer. Pathology, research and practice 26 32534701
2012 Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis. Gene 26 22890139
2015 Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes. Blood cells, molecules & diseases 25 25976471
2005 Hemochromatosis with mutation of the ferroportin 1 (IREG1) gene. Internal medicine (Tokyo, Japan) 24 15897636
2002 The expression and regulation of the iron transport molecules hephaestin and IREG1: implications for the control of iron export from the small intestine. Cell biochemistry and biophysics 24 12139399
2016 Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis. International journal of hematology 23 27896572
2019 Increased DMT1 and FPN1 expression with enhanced iron absorption in ulcerative colitis human colon. American journal of physiology. Cell physiology 22 31721611
2018 The SLC40A1 R178Q mutation is a recurrent cause of hemochromatosis and is associated with a novel pathogenic mechanism. Haematologica 21 30002125
2022 Etoposide in combination with erastin synergistically altered iron homeostasis and induced ferroptotic cell death through regulating IREB2/FPN1 expression in estrogen receptor positive-breast cancer cells. Life sciences 20 36442526
2021 Upregulation of miR-18a-5p promotes the proliferation of prostate cancer via inhibiting the expression of SLC40A1. Pathology, research and practice 20 34098197
2004 Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in hereditary haemochromatosis. Gut 20 15247188
2020 Extending the Shelf-Life of Meat and Dairy Products via PET-Modified Packaging Activated With the Antimicrobial Peptide MTP1. Frontiers in microbiology 19 31993029
2018 A novel SLC40A1 p.Y333H mutation with gain of function of ferroportin: A recurrent cause of haemochromatosis in China. Liver international : official journal of the International Association for the Study of the Liver 19 30500107
2012 Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating serum hepcidin levels in Rwandese HIV-positive women. Annals of hematology 18 22249207
2007 Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV. Blood cells, molecules & diseases 18 17997113
2025 Lignans from Schisandra chinensis (Turcz.) Baill ameliorates cognitive impairment in Alzheimer's disease and alleviates ferroptosis by activating the Nrf2/FPN1 signaling pathway and regulating iron levels. Journal of ethnopharmacology 17 39798677
2025 Picropodophyllin induces ferroptosis via blockage of AKT/NRF2/SLC7A11 and AKT/NRF2/SLC40A1 axes in hepatocellular carcinoma as a natural IGF1R inhibitor. Phytomedicine : international journal of phytotherapy and phytopharmacology 16 40412057
2024 Inhibiting DNA methyltransferase DNMT3B confers protection against ferroptosis in nucleus pulposus and ameliorates intervertebral disc degeneration via upregulating SLC40A1. Free radical biology & medicine 16 38705495
2023 IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2/FPN1 signaling axis depended on NFKB2. iScience 16 37520713
2008 Does the SLC40A1 gene modify HFE-related haemochromatosis phenotypes? Annals of hematology 16 18820912
2024 Asiatic acid ameliorates doxorubicin-induced cardiotoxicity by promoting FPN-mediated iron export and inhibiting ferroptosis. Acta pharmacologica Sinica 15 39143234
2019 Acupuncture protects from 6-OHDA-induced neuronal damage by balancing the ratio of DMT1/Fpn1. Saudi journal of biological sciences 14 31889778
2018 Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN). eNeuro 14 29379878
2015 Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4. Internal medicine journal 13 26059880
2011 SLC40A1 Q248H allele frequencies and associated SLC40A1 haplotypes in three West African population samples. Annals of human biology 13 21231898
2007 SLC40A1 c.1402G-->a results in aberrant splicing, ferroportin truncation after glycine 330, and an autosomal dominant hemochromatosis phenotype. Acta haematologica 13 18160816
2004 Differences in the uptake of iron from Fe(II) ascorbate and Fe(III) citrate by IEC-6 cells and the involvement of ferroportin/IREG-1/MTP-1/SLC40A1. Pflugers Archiv : European journal of physiology 13 15114483
2017 Type 4B hereditary hemochromatosis associated with a novel mutation in the SLC40A1 gene: A case report and a review of the literature. Medicine 12 28930842
2025 Oligodendrocyte-specific knockout of FPN1 affects CNS myelination defects and depression-like behavior in mice. Free radical biology & medicine 11 40609802
2024 Human umbilical cord mesenchymal stem cells protect against ferroptosis in acute liver failure through the IGF1-hepcidin-FPN1 axis and inhibiting iron loading. Acta biochimica et biophysica Sinica 11 38273781
2024 Identification of SLC40A1, LCN2, CREB5, and SLC7A11 as ferroptosis-related biomarkers in alopecia areata through machine learning. Scientific reports 11 38360836
2023 PAC-Net: Multi-pathway FPN with position attention guided connections and vertex distance IoU for 3D medical image detection. Frontiers in bioengineering and biotechnology 11 36815901
2023 Transcriptomic analysis identified SLC40A1 as a key iron metabolism-related gene in airway macrophages in childhood allergic asthma. Frontiers in cell and developmental biology 11 37123407
2023 Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52. Journal of pharmaceutical analysis 11 38352945
2022 Leonurine suppresses prostate cancer growth in vitro and in vivo by regulating miR-18a-5p/SLC40A1 axis. The Chinese journal of physiology 11 36588358
2017 Detection of melanoma metastases with PET-Comparison of 18F-5-FPN with 18F-FDG. Nuclear medicine and biology 11 28433794
2013 Cadmium Transport in a Model of Neonatal Intestinal Cells Correlates to MRP1 and Not DMT1 or FPN1. ISRN toxicology 11 23724302
2010 Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating plasma tumor necrosis factor-alpha and macrophage migration inhibitory factor concentrations in African children. Clinica chimica acta; international journal of clinical chemistry 11 20460119
2025 WWOX-mediated p53/SAT1 and NRF2/FPN1 axis contribute to toosendanin-induced ferroptosis in hepatocellular carcinoma. Biochemical pharmacology 10 39894307
2023 YOLOv5-FPN: A Robust Framework for Multi-Sized Cell Counting in Fluorescence Images. Diagnostics (Basel, Switzerland) 10 37443674
2023 Protective effect of Angelica sinensis polysaccharide on pregnant rats suffering from iron deficiency anemia via regulation of the hepcidin-FPN1 axis. International journal of biological macromolecules 10 37967601
2014 A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro. American journal of hematology 10 24644245
2011 Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man. European journal of haematology 10 21175851
2011 Genetic polymorphisms in bovine transferrin receptor 2 (TFR2) and solute carrier family 40 (iron-regulated transporter), member 1 (SLC40A1) genes and their association with beef iron content. Animal genetics 10 22404347
2008 Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G. Acta haematologica 10 19066423
2017 Characterization of three novel pathogenic SLC40A1 mutations and genotype/phenotype correlations in 7 Italian families with type 4 hereditary hemochromatosis. Biochimica et biophysica acta. Molecular basis of disease 8 29154924
2012 Mild iron overload in an African American man with SLC40A1 D270V. Acta haematologica 8 22584997
2025 The molecular mechanism by which CTSB degrades FPN to disrupt macrophage iron homeostasis and promote the progression of atherosclerosis. Molecular and cellular biochemistry 7 39960586
2024 The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain. Journal of advanced research 7 38527587
2022 Associated Effect of SLC40A1 and TMPRSS6 Polymorphisms on Iron Overload. Metabolites 7 36295822
2020 Splicing analysis of SLC40A1 missense variations and contribution to hemochromatosis type 4 phenotypes. Blood cells, molecules & diseases 7 33341511
2025 Dexmedetomidine Inhibits Ferroptosis to Alleviate Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Regulating the HDAC2/FPN Pathway. Cardiovascular drugs and therapy 6 39747742
2024 The dual loss and gain of function of the FPN1 iron exporter results in the ferroportin disease phenotype. HGG advances 6 39039793
2023 The Spectra of Disease-Causing Mutations in the Ferroportin 1 (SLC40A1) Encoding Gene and Related Iron Overload Phenotypes (Hemochromatosis Type 4 and Ferroportin Disease). Human mutation 6 40225168
2021 Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: a case report. BMC gastroenterology 6 33673803
2025 Epigenetic suppression of Nrf2-Slc40a1 axis induces ferroptosis and enhances immunotherapy in pancreatic cancer. Journal for immunotherapy of cancer 5 41135950

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