Affinage

FCGRT

IgG receptor FcRn large subunit p51 · UniProt P55899

Length
365 aa
Mass
39.7 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FcRn (encoded by FCGRT) is an MHC class I-related α-chain that heterodimerizes with β2-microglobulin and functions as the principal pH-dependent receptor for IgG and albumin homeostasis, mucosal immunity, and transplacental IgG transfer. FcRn binds IgG at the CH2–CH3 domain interface and albumin at acidic endosomal pH (~6.0) while releasing both ligands at neutral pH (~7.4), thereby diverting them from lysosomal degradation into Rab11-positive recycling endosomes and SNX5-positive tubular carriers for return to the cell surface (PMID:14764666, PMID:11847107, PMID:31444284, PMID:28637874). In polarized epithelia and endothelia—including intestinal, placental, and endothelial cells—FcRn additionally mediates bidirectional transcytosis of IgG, with transcytosis directionality regulated by ligand-induced receptor redistribution and dependent on microtubules and PI3-kinase signaling (PMID:10510331, PMID:11182218, PMID:20525015). Beyond IgG/albumin salvage, FcRn enhances neutrophil phagocytosis of IgG-opsonized bacteria in a pH-dependent manner, serves as a primary receptor for echovirus entry, and its hepatic expression directs polarized albumin secretion and recycling; FcRn is subject to transcriptional regulation by NF-κB, Sp1, Zbtb7a, and post-transcriptional regulation by miR-3181, and is targeted for ER-associated degradation by the HCMV immune evasin US11 (PMID:16849638, PMID:33513208, PMID:28330995, PMID:31209240, PMID:29302759, PMID:31289263).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1997 Medium

    Establishing that FcRn is expressed in human adult and fetal intestinal epithelium resolved the question of whether the neonatal Fc receptor, initially studied in rodents, also operates in human gut, opening the field to studying its mucosal immune function in humans.

    Evidence RT-PCR, Western blot, and immunohistochemistry of human fetal and adult intestinal tissue

    PMID:9370926

    Open questions at the time
    • No direct functional transport assay performed
    • Expression levels across intestinal segments not quantified
  2. 1998 High

    Demonstrating that FcRn is expressed in endothelial cells within intracellular vesicles established that vascular endothelium—not just epithelium—is the principal site of IgG homeostatic regulation in the adult.

    Evidence Immunohistochemistry, immunoprecipitation, and immunofluorescence of murine endothelial cells

    PMID:9786428

    Open questions at the time
    • Human endothelial expression not directly shown in this study
    • Mechanism of IgG sorting not yet addressed
  3. 1999 High

    Showing that FcRn mediates bidirectional, pH-dependent IgG transcytosis across polarized human intestinal epithelial cells established FcRn as a mucosal IgG transport receptor in humans, not merely a salvage receptor.

    Evidence Transcytosis assays in polarized T84 monolayers with endosomal acidification inhibition

    PMID:10510331

    Open questions at the time
    • In vivo confirmation of bidirectional transport in human intestine not yet available
    • Relative contribution of apical-to-basolateral vs. basolateral-to-apical flux not quantified in vivo
  4. 2000 High

    Mapping the FcRn binding site to the IgG1 Fc CH2–CH3 domain interface via systematic alanine-scanning mutagenesis defined the molecular footprint governing FcRn-IgG interaction and enabled rational Fc engineering.

    Evidence Alanine-scanning mutagenesis of IgG1 Fc with SPR and ELISA binding assays for FcRn and other FcγRs

    PMID:11096108

    Open questions at the time
    • Full structural model of the human FcRn–IgG complex not yet available at this time
    • Contribution of IgG variable regions not addressed
  5. 2002 High

    Reconstitution in polarized MDCK cells revealed that FcRn-mediated transcytosis involves ligand-induced receptor redistribution and routing through Rab11-positive recycling endosomes, with basolateral recycling dependent on PI3-kinase, establishing the intracellular trafficking itinerary of FcRn.

    Evidence Pulse-chase, confocal microscopy, and wortmannin inhibition in polarized MDCK cells expressing rat FcRn

    PMID:11847107

    Open questions at the time
    • Human FcRn trafficking may differ from rat FcRn in this heterologous system
    • Identity of adaptor proteins linking FcRn to sorting machinery unknown
  6. 2004 High

    Live-cell imaging in human endothelial cells demonstrated that FcRn sorts IgG away from multivesicular bodies destined for lysosomes and into recycling tubules, providing direct visualization of the IgG salvage mechanism.

    Evidence Live-cell imaging of FcRn-GFP in human endothelial cells with fluorescent IgG tracking

    PMID:14764666

    Open questions at the time
    • Molecular determinants of FcRn exit from sorting endosomes not identified
    • Quantitative stoichiometry of salvage vs. degradation not measured
  7. 2004 Medium

    Identification of Sp1, NF1, and Ets binding sites in the Fcgrt promoter with opposing regulatory activities established that FcRn expression is actively controlled at the transcriptional level with tissue- and developmental-stage-specific modulation.

    Evidence Luciferase reporter assays, EMSA, and site-directed mutagenesis of the mouse Fcgrt promoter

    PMID:15627500

    Open questions at the time
    • Mouse promoter elements may not fully recapitulate human FCGRT regulation
    • In vivo relevance of each transcription factor binding site not confirmed
  8. 2006 High

    Two discoveries broadened FcRn biology beyond recycling: FcRn expression in neutrophil granules with relocation to phagolysosomes established a role in innate immunity via enhanced phagocytosis, while the YTE Fc mutation demonstrated that engineered FcRn affinity enhancement extends IgG half-life in primates, validating FcRn as a therapeutic target.

    Evidence FcRn-KO and β2M-KO neutrophil phagocytosis assays with IgG-opsonized bacteria; Fc-YTE mutagenesis with in vitro binding and in vivo PK in cynomolgus monkeys

    PMID:16793771 PMID:16849638

    Open questions at the time
    • Mechanism by which FcRn enhances phagocytosis in the acidic phagolysosome not fully defined
    • Long-term immunological consequences of YTE-mediated extended half-life not assessed
  9. 2009 High

    Showing that oxidation of Met252 and Met428 at the Fc–FcRn interface reduces FcRn binding established that post-translational modifications of IgG can modulate FcRn-dependent serum persistence.

    Evidence In vitro methionine oxidation of IgG2 Fc followed by SPR/ELISA binding to FcRn and Protein A

    PMID:19165723

    Open questions at the time
    • In vivo significance of methionine oxidation on IgG half-life not directly tested
    • Whether FcRn itself undergoes oxidative modifications affecting function is unknown
  10. 2015 High

    Quantitative SPR demonstrated that two FcRn molecules bind independently to both Fc sites of an IgG homodimer with identical affinity (~760 nM at pH 5.8), and that a neutral-pH affinity threshold governs whether enhanced acidic-pH binding translates to extended or shortened half-life, establishing the biophysical rules for Fc half-life engineering.

    Evidence Artifact-controlled SPR with stoichiometric analysis; Fc mutagenesis panel with PK in hFcRn transgenic mice and cynomolgus monkeys

    PMID:25538249 PMID:25658443

    Open questions at the time
    • How avidity at the membrane surface modifies these solution-phase affinity rules is not fully resolved
    • The pH 7.4 threshold value may differ for non-IgG1 subclasses
  11. 2017 High

    Three studies converged to establish FcRn as a dual IgG/albumin homeostatic receptor: liver-specific FcRn deletion caused hypoalbuminemia and biliary albumin loss; FcRn-dependent endosomal sorting diverted albumin from lysosomes to recycling compartments with affinity-tunable efficiency; and IgG variable-domain CDRs were shown to modulate FcRn binding up to 79-fold beyond canonical Fc determinants.

    Evidence Liver-specific FcRn-KO mice with pharmacological blockade; albumin recycling assays with affinity-engineered variants in endothelial cells; SPR panel of >50 IgGs with identical Fc domains and PK in hFcRn transgenic mice

    PMID:28330995 PMID:28637874 PMID:28991504

    Open questions at the time
    • Structural basis for CDR-mediated modulation of FcRn binding not determined
    • Relative contribution of hepatic vs. endothelial FcRn to systemic albumin homeostasis not quantified
  12. 2018 High

    Tracking albumin fusion proteins through Rab11+ recycling endosomes confirmed the FcRn-dependent endosomal salvage route operates for albumin-conjugated therapeutics, while miR-3181 was identified as a post-transcriptional repressor of FCGRT expression.

    Evidence Confocal microscopy with Rab11/EEA1 markers and FcRn-defective albumin variants; luciferase 3′-UTR reporter assay with miR-3181 mimic/inhibitor in multiple cell lines

    PMID:29302759 PMID:29523681

    Open questions at the time
    • In vivo relevance of miR-3181 regulation of FcRn not demonstrated
    • Whether other miRNAs coordinately regulate FCGRT is unknown
  13. 2019 High

    Three findings expanded FcRn biology: in macrophages, FcRn rescues IgG and albumin via SNX5-positive macropinosome tubules distinct from FcγR-mediated uptake; HCMV US11 protein targets FcRn for ER-associated degradation via Derlin-1/TMEM129/UbE2J2 to evade antibody-mediated immunity; and DNA methylation of CpG sites in the FCGRT promoter modulates Zbtb7a/Sp1 binding and FcRn expression levels.

    Evidence Live-cell imaging in primary macrophages with SNX5/Rab11 markers; co-IP identifying ERAD components with transcytosis assays during HCMV infection; ChIP, luciferase reporters, and methylation analysis in cell lines and human tissues

    PMID:31209240 PMID:31289263 PMID:31444284

    Open questions at the time
    • Whether other herpesviruses employ analogous FcRn evasion strategies is unknown
    • Functional significance of SNX5 vs. Rab11 route selectivity not defined
  14. 2021 Medium

    Demonstrating that human FcRn serves as the primary entry receptor for Echovirus 11 in transgenic mice—with pathogenesis requiring concomitant loss of type I IFN signaling—established FcRn as a dual-use receptor exploited by enteroviruses.

    Evidence hFcRn transgenic and IFNAR-KO mice infected with echovirus, with Luminex profiling and histopathology

    PMID:33513208

    Open questions at the time
    • Structural basis of echovirus–FcRn interaction not resolved
    • Whether FcRn-mediated transcytosis facilitates viral dissemination not directly tested
  15. 2022 High

    Crystal structure of an engineered Fc/FcRn complex revealed that the IgG Fab domain sterically impairs FcRn interaction in a membrane context, explaining why Fc-only fragments occupy FcRn more efficiently than full-length IgG—informing FcRn antagonist design.

    Evidence X-ray crystallography of Fc-MST-HN/FcRn complex with cell-based FcRn occupancy assays and in vivo IgG reduction in cynomolgus monkeys

    PMID:36241613

    Open questions at the time
    • Full-length IgG/FcRn co-structure on membrane not yet available
    • How Fab glycosylation synergizes with steric hindrance mechanistically is unclear
  16. 2024 Medium

    Two studies connected FcRn to metabolic disease and therapeutic mechanism: FcRn-dependent IgG recycling in adipose progenitor cells and macrophages drives obesity-associated IgG accumulation that impairs insulin receptor signaling, while different FcRn antagonists were shown to reduce albumin levels through distinct mechanisms—FcRn degradation versus direct competition for albumin binding.

    Evidence Diet-induced obesity mouse models with FcRn targeting and insulin signaling assays; cellular panel comparison of FcRn antagonists with degradation and competitive binding assays

    PMID:38713534 PMID:39674176

    Open questions at the time
    • AI-assisted modeling of IgG–insulin receptor interaction awaits experimental structural validation
    • Clinical translation of FcRn targeting for insulin resistance not tested
    • Relative importance of FcRn degradation vs. competition for albumin binding in patients not determined
  17. 2025 High

    The crystal structure of nipocalimab Fab bound to FcRn defined a unique pH-independent epitope on the IgG-binding site, explaining how this antagonist selectively blocks IgG recycling without affecting other immunoglobulin classes, providing a structural framework for selective FcRn antagonism.

    Evidence Crystal structure of nipocalimab Fab/FcRn complex with cell-based FcRn occupancy and in vivo dose-response in mice and monkeys

    PMID:39936406

    Open questions at the time
    • Long-term effects of sustained pH-independent FcRn blockade on albumin levels not fully characterized
    • Whether epitope differences among FcRn antagonists produce distinct clinical efficacy profiles is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of simultaneous IgG and albumin co-binding and sorting on the same FcRn molecule, the identity of adaptor proteins linking FcRn cytoplasmic tail to endosomal sorting machinery, and the quantitative contribution of FcRn in specific tissues (e.g., liver vs. endothelium vs. hematopoietic cells) to systemic IgG and albumin homeostasis.
  • No full-length IgG/albumin/FcRn co-structure on membranes
  • Adaptor proteins for FcRn cytoplasmic tail sorting signals not identified
  • Tissue-specific conditional knockout studies with quantitative PK modeling incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 5 GO:0005215 transporter activity 4
Localization
GO:0005768 endosome 5 GO:0031410 cytoplasmic vesicle 4 GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3
Partners
B2MRAB11SNX5
Complex memberships
FcRn–β2-microglobulin heterodimer

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 FcRn mediates bidirectional, pH-dependent, receptor-specific transcytosis of IgG across polarized human intestinal epithelial cells (T84 line), establishing a mechanism for IgG transport at mucosal surfaces in adult humans. Solute flux/transcytosis assays in polarized T84 monolayers, immunocytochemistry, endosomal acidification inhibition The Journal of clinical investigation High 10510331
1998 FcRn is functionally expressed in endothelial cells of mice, localized within cytosolic vesicular structures, and is the site at which serum IgG homeostasis is maintained. Immunohistochemistry, immunoprecipitation, immunofluorescence of cultured murine endothelial cells, tissue distribution of FcRn-binding proteins International immunology High 9786428
2004 FcRn segregates IgG-FcRn complexes from unbound IgG in sorting endosomes; FcRn-IgG complexes are depleted from sorting endosomes generating multivesicular bodies destined for lysosomal degradation, while rescued IgG is recycled. FcRn trafficking overlaps with the transferrin receptor pathway. Live cell imaging of FcRn-GFP transfected human endothelial cells, fluorescence microscopy Journal of immunology High 14764666
2000 The FcRn binding site on human IgG1 was mapped to the CH2-CH3 domain interface of the Fc region; key residues were identified that, when mutated, abrogated or enhanced binding to FcRn (and other FcγRs). Alanine-scanning mutagenesis of IgG1 Fc combined with binding assays (ELISA, SPR) for FcγRI, FcγRII, FcγRIII, and FcRn The Journal of biological chemistry High 11096108
2006 FcRn is expressed in azurophilic and specific granules of neutrophils, relocates to phagolysosomes upon phagocytosis of IgG-opsonized bacteria, and enhances phagocytosis in a pH-dependent, IgG-recycling-independent manner; FcRn-deficient neutrophils show impaired phagocytosis. FcRn-knockout and β2M-knockout mouse neutrophils, phagocytosis assays, IgG H435A mutant (FcRn-binding-deficient), TAT-peptide inhibition of intracellular FcRn motifs Blood High 16849638
2006 The M252Y/S254T/T256E (YTE) triple mutation in the IgG1 Fc domain increases binding to human and cynomolgus FcRn 10-fold at pH 6.0 while preserving release at pH 7.4, resulting in ~4-fold increased serum half-life and increased lung bioavailability in primates. In vitro FcRn binding assays (pH-dependent), pharmacokinetic studies in cynomolgus monkeys, ADCC assays The Journal of biological chemistry High 16793771
2001 Human placental endothelial cells express functional FcRn and mediate transcytosis of IgG preferentially from the basolateral to apical compartment; IgG and FcRn co-localize in a chloroquine-sensitive intracellular endocytic compartment. Indirect immunofluorescence, RT-PCR, 125I-IgG transcytosis assay in double-chamber system, electron microscopy with colloidal gold Human immunology High 11182218
2002 FcRn expressed in polarized MDCK cells mediates IgG transcytosis and recycling; in the absence of IgG, FcRn distributes predominantly apically, but redistributes to basolateral locations upon IgG binding—indicating ligand-induced redistribution signaling transcytosis. PI3-kinase inhibition disrupts basolateral but not apical recycling; apically internalized IgG recycles mainly from wortmannin-insensitive apical early endosomes, while transcytosing IgG passes through Rab11-positive apical recycling endosomes. Pulse-chase experiments, confocal microscopy, quantitative IgG transport assays, pharmacological inhibitors (wortmannin) in polarized MDCK cells expressing rat FcRn The EMBO journal High 11847107
2009 Methionine oxidation at Met252 and Met428 in the IgG2 Fc region decreases binding affinity to both FcRn and Protein A, establishing that these solvent-exposed methionine residues at the FcRn binding interface are critical for the FcRn-IgG interaction. In vitro oxidation kinetics, binding affinity measurements (SPR/ELISA) for FcRn and Protein A Protein science High 19165723
2015 Two FcRn molecules bind an IgG homodimer independently and with identical affinities at the two Fc sites (KD ~760 nM at pH 5.8 for human FcRn/human IgG1); in vivo serum half-life is influenced by both affinity and avidity of FcRn-IgG interactions. Surface plasmon resonance biosensor assays (artifact-controlled), in vivo PK in mouse and rat models mAbs High 25658443
2014 An FcRn binding affinity threshold at neutral pH (pH 7.4) governs IgG recycling efficiency: Fc variants with acidic pH-enhanced binding but neutral-pH affinity below this threshold exhibit extended serum half-life, while those with neutral-pH affinity above the threshold show rapid clearance. Fc mutagenesis panel, SPR binding at pH 6.0 and 7.4, pharmacokinetic studies in human FcRn transgenic mice and cynomolgus monkeys The Journal of biological chemistry High 25538249
2017 Hepatic FcRn mediates basal recycling and bidirectional transcytosis of albumin and directs newly synthesized albumin into the basal (blood-side) milieu; liver-specific or global FcRn deletion causes hypoalbuminemia, biliary albumin loss, and intracellular albumin accumulation, and paradoxically protects from APAP-induced liver injury by increased intracellular albumin scavenging of reactive oxygen species. Global and liver-specific FcRn-knockout mice, in vitro polarized cell models, pharmacological FcRn blockade with mAbs and peptide mimetics, biochemical fractionation Proceedings of the National Academy of Sciences of the United States of America High 28330995
2017 FcRn-driven endosomal sorting directs albumin away from lysosomes: albumin with high FcRn-binding affinity is preferentially sorted to recycling (not lysosomal) compartments, with ~3.3-fold more recycled back to the medium compared to wild-type albumin, demonstrating the FcRn-dependent endosomal salvage pathway for albumin. Flow cytometry, quantitative confocal microscopy, albumin-recycling assay using wild-type and engineered albumins with varied FcRn affinities in low- and high-FcRn-expressing endothelial cell lines The Journal of biological chemistry High 28637874
2019 FcRn rescues albumin and IgG from degradation by mediating their rapid recycling from early macropinosomes via SNX5-positive membrane domains and tubular carriers to the plasma membrane in primary macrophages; IgG endocytosed by macropinocytosis follows this pathway, distinct from IgG bound to surface FcγRs. Primary mouse macrophages selectively expressing human FcRn, live-cell imaging, confocal microscopy, fluorescent albumin/IgG tracking, SNX5/Rab11 marker co-localization Journal of cell science High 31444284
2018 The albumin fusion protein rIX-FP is recycled by FcRn via the albumin moiety: following internalization at low pH, rIX-FP traffics into Rab11+ recycling endosomes (within 10–15 min) and is exported from the cell; an FcRn interaction-defective albumin variant localizes to lysosomes instead. Confocal microscopy, Rab11/EEA1 co-localization, FcRn-positive vs. negative cell lines, albumin variants with FcRn-defective mutations The Journal of biological chemistry High 29523681
2017 Complementarity-determining regions (CDRs) of IgG variable domains, particularly CDR-L3, significantly alter IgG affinity for FcRn (up to 79-fold variation) and correlate with in vivo IgG clearance in human FcRn transgenic mice, beyond the canonical Fc CH2-CH3 binding interface. SPR steady-state binding assay of >50 IgG molecules with identical Fc domains but different variable regions, in vivo PK in hFcRn transgenic mice mAbs High 28991504
2019 Human cytomegalovirus US11 protein inhibits FcRn assembly with β2-microglobulin, retains FcRn in the ER, and recruits ubiquitin enzymes Derlin-1, TMEM129, and UbE2J2 to initiate ER-associated degradation (ERAD) of FcRn, thereby blocking FcRn trafficking to endosomes and reducing IgG transcytosis and IgG half-life. Co-immunoprecipitation, Western blot, IgG transcytosis assays in FcRn-expressing intestinal/placental epithelial and endothelial cells, HCMV infection experiments Nature communications High 31289263
2010 Endogenous FcRn is distributed predominantly throughout the endosomal system at steady state, with only a low percentage at the plasma membrane; a fraction of cell-surface FcRn is endocytosis-resistant while the remainder undergoes rapid endocytosis and is replenished from an internal pool. Live-cell imaging, antibody feeding assays, FACS, fluorescence microscopy of cells expressing endogenous FcRn PloS one Medium 28817705
2010 FcRn-expressing MDCK cells show that FcRn and pIgR traffic through partly overlapping endosomal compartments (EEA1+, Rab11+, transferrin-positive recycling endosomes) but with directional differences; FcRn-mediated apical-to-basolateral IgG transcytosis depends on microtubules similarly to pIgR-mediated basolateral-to-apical transport. Confocal fluorescence microscopy, pulse-chase in co-transfected MDCK cells, live-cell imaging, microtubule depolymerization Traffic Medium 20525015
2015 FcRn mediates transplacental transport of IgE in the form of IgG anti-IgE/IgE immune complexes (but not monomeric IgE); IgG anti-IgE/IgE complexes bind to and are transcytosed by FcRn-expressing MDCK cells in an FcRn-dependent manner. FcRn-transfected MDCK cell transcytosis assays, clinical correlation of maternal/cord blood IgG anti-IgE/IgE IC levels Clinical and experimental allergy Medium 25652137
2022 The Fab region of full-length IgG impairs interaction with membrane-associated FcRn (but not soluble FcRn in cell-free assays), reducing intracellular FcRn occupancy compared to Fc-only fragments; the crystal structure of Fc-MST-HN/FcRn provides a structural explanation for why the Fab disrupts binding in the membrane context. Crystal structure determination of Fc-MST-HN/FcRn complex, cell-based FcRn binding assays, intracellular accumulation measurements, SPR (cell-free), in vivo IgG reduction in cynomolgus monkeys Nature communications High 36241613
2023 IgG Fab glycosylation hinders FcRn-mediated transplacental transport (~20% reduction); in a cell membrane context (but not in cell-free SPR assays) Fab glycans negatively impact IgG-FcRn interaction and reduce transcytosis efficiency. SPR, FcRn affinity chromatography (cell-free), cell membrane-context binding assays, clinical measurement of placental transfer of Fab-glycosylated IgG Journal of immunology High 36480251
2004 The mouse Fcgrt 5' proximal promoter contains at least two upstream regulatory regions with repressor/activator functions; transcription factors NF1, Sp1 (GT box), and Ets bind regulatory motifs; Sp1 binding to the GT box up-regulates promoter activity, while Ets binding represses it; NF1 binding differs between neonatal enterocytes and adult cells, suggesting tissue/developmental regulation of FcRn expression. Reporter gene (luciferase) assays, electrophoretic mobility shift assay (EMSA), site-directed mutagenesis of promoter elements Biochimica et biophysica acta Medium 15627500
2018 MicroRNA hsa-miR-3181 directly binds the 3'-UTR of FCGRT and reduces FCGRT mRNA and FcRn protein expression in multiple human cell lines (A549, HEK293, HepG2), identifying it as an epigenetic regulator of FcRn. Luciferase reporter assay with FCGRT 3'-UTR, microRNA mimic/inhibitor transfection, RT-qPCR, Western blot Pharmaceutical research Medium 29302759
2019 DNA methylation in the FCGRT regulatory region (−1058 to −587 bp) contributes to variable FcRn expression; CpG site methylation reduces binding of methylation-sensitive transcription factors Zbtb7a and Sp1, shown by chromatin immunoprecipitation in model cell lines. Quantitative DNA methylation analysis, luciferase reporter assays, chromatin immunoprecipitation (ChIP), RT-qPCR, human liver/myocardium tissue samples Scientific reports Medium 31209240
2016 TGEV infection of porcine intestinal epithelial cells (IPEC-J2) up-regulates FcRn expression via activation of NF-κB signaling; four NF-κB binding sites in the pFcRn promoter were functionally validated by luciferase reporter, ChIP, EMSA, and supershift assays; NF-κB inhibition with BAY 11-7082 reversed this up-regulation. Luciferase reporter assay, ChIP, EMSA, supershift assay, NF-κB inhibitor (BAY 11-7082), RT-qPCR in IPEC-J2 cells Scientific reports Medium 27555521
2025 Nipocalimab (anti-FcRn antibody) binds a unique epitope on the IgG-binding site of FcRn with pH-independent high affinity; its crystal structure (Fab/FcRn complex) reveals the structural basis for pH-independent binding, distinguishing it mechanistically from other FcRn antagonists; it selectively reduces IgG without affecting other immunoglobulin classes or immune functions. Crystal structure of nipocalimab Fab/FcRn complex, cell-based FcRn occupancy assays, in vivo dose-response studies in mice and cynomolgus monkeys mAbs High 39936406
2024 Different FcRn antagonists differentially affect albumin homeostasis through two mechanisms: (1) increased degradation of FcRn itself (reducing overall FcRn-mediated recycling of albumin) and (2) direct competition between the antagonist and albumin for FcRn binding, with the relative contribution of each mechanism varying by antagonist. Cellular and molecular analyses of a panel of FcRn antagonists, FcRn degradation assays, competitive binding assays JCI insight Medium 38713534
2024 FcRn-dependent IgG recycling in adipose progenitor cells and macrophages governs IgG accumulation in adipose tissue during obesity; this accumulated IgG interacts with the insulin receptor ectodomain via its Fc-CH3 domain, hindering insulin binding and impairing insulin signaling; targeting FcRn abolished IgG accumulation and corrected insulin resistance in diet-induced obesity. Diet-induced obesity mouse models, FcRn targeting in vivo, AI-assisted modeling of IgG/insulin receptor interaction, in vitro insulin signaling assays, macrophage/progenitor cell analyses Cell metabolism Medium 39674176
2005 FcRn is expressed in normal human epidermal keratinocytes, localized in cytoplasmic vesicular/granular structures predominantly intracellularly, and binds human IgG in an Fc-dependent, pH-dependent manner (at acidic pH). RT-PCR, Northern blot, immunoblot, immunoprecipitation, immunofluorescence microscopy, FACS, IgG binding assay at acidic pH The Journal of investigative dermatology Medium 15654966
1997 FcRn is expressed on human intestinal epithelial cells (fetal and adult), localized predominantly in the apical region of enterocytes, consistent with its role in IgG binding and transport. RT-PCR, Western blot, immunohistochemistry of human fetal and adult intestinal tissue Immunology Medium 9370926
2021 Human FcRn expression is required for Echovirus 11 (E11) pathogenesis in mice; hFcRn serves as the primary receptor for echoviruses, but hFcRn expression alone is insufficient for susceptibility—ablation of type I IFN signaling in addition to hFcRn expression recapitulates echovirus pathogenesis and liver damage observed in humans. hFcRn transgenic mice, IFNAR-knockout mice, in vivo echovirus infection, Luminex multianalyte profiling, histopathology PLoS pathogens Medium 33513208

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 FcRn: the neonatal Fc receptor comes of age. Nature reviews. Immunology 1779 17703228
2000 High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. The Journal of biological chemistry 920 11096108
2006 Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). The Journal of biological chemistry 508 16793771
2000 Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annual review of immunology 358 10837074
1999 Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. The Journal of clinical investigation 330 10510331
2019 The Neonatal Fc Receptor (FcRn): A Misnomer? Frontiers in immunology 325 31354709
1997 Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells. Immunology 248 9370926
2004 Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn. Journal of immunology (Baltimore, Md. : 1950) 245 14764666
2015 Unraveling the Interaction between FcRn and Albumin: Opportunities for Design of Albumin-Based Therapeutics. Frontiers in immunology 244 25674083
2019 Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology 216 31118245
2013 Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Critical reviews in biotechnology 201 24156398
1998 Functional expression of the MHC class I-related receptor, FcRn, in endothelial cells of mice. International immunology 201 9786428
2015 The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy. Advanced drug delivery reviews 181 25703189
1997 FcRn: the MHC class I-related receptor that is more than an IgG transporter. Immunology today 165 9425738
2009 Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn. Protein science : a publication of the Protein Society 159 19165723
2015 The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity. mAbs 158 25658443
2006 Perspective-- FcRn transports albumin: relevance to immunology and medicine. Trends in immunology 157 16731041
2017 Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy. Frontiers in immunology 146 29163461
2001 Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells. Human immunology 145 11182218
2019 Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. American journal of hematology 144 31821591
2006 FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis. Blood 142 16849638
2017 Distribution of FcRn Across Species and Tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 138 28402755
2018 M281, an Anti-FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety Across the Full Range of IgG Reduction in a First-in-Human Study. Clinical pharmacology and therapeutics 118 30402880
2009 Chapter 4: Multitasking by exploitation of intracellular transport functions the many faces of FcRn. Advances in immunology 111 19755184
2018 Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. mAbs 103 30130439
2014 The Role of FcRn in Antigen Presentation. Frontiers in immunology 102 25221553
2019 Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses. Science advances 101 31897428
2020 Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations. The Journal of allergy and clinical immunology 99 32896308
2009 Immune and non-immune functions of the (not so) neonatal Fc receptor, FcRn. Seminars in immunopathology 99 19495758
2018 Targeting FcRn to Generate Antibody-Based Therapeutics. Trends in pharmacological sciences 94 30143244
2009 Investigation of the influence of FcRn on the distribution of IgG to the brain. The AAPS journal 94 19636712
2016 Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. mAbs 89 27232760
2021 The importance of FcRn in neuro-immunotherapies: From IgG catabolism, FCGRT gene polymorphisms, IVIg dosing and efficiency to specific FcRn inhibitors. Therapeutic advances in neurological disorders 86 33717213
2017 Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury. Proceedings of the National Academy of Sciences of the United States of America 83 28330995
2014 pH-dependent binding engineering reveals an FcRn affinity threshold that governs IgG recycling. The Journal of biological chemistry 82 25538249
2015 The multiple facets of FcRn in immunity. Immunological reviews 81 26497526
2022 Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders. Frontiers in immunology 75 35757719
2014 FcRn: from molecular interactions to regulation of IgG pharmacokinetics and functions. Current topics in microbiology and immunology 74 25116104
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