Affinage

Showing FCGRT — FCRN is a alias.

FCGRT

IgG receptor FcRn large subunit p51 · UniProt P55899

Length
365 aa
Mass
39.7 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FCGRT encodes the alpha chain of FcRn, an MHC class I-related receptor that, in heterodimer with beta2-microglobulin, binds IgG and albumin at two distinct, non-overlapping sites in a strictly pH-dependent manner and salvages both ligands from lysosomal degradation by recycling and transcytosing them (PMID:16605266, PMID:16849638, PMID:28330995). IgG engages FcRn through residues at the CH2-CH3 Fc interface contacting the FcRn alpha2 domain (PMID:11096108), whereas albumin binds a separate, predominantly hydrophobic surface organized around a cluster of conserved tryptophans and a pH-sensitive loop (PMID:24764301); the IgG and albumin sites are independent and bind non-cooperatively, with two FcRn molecules engaging one IgG at symmetrical sites (PMID:16605266, PMID:25658443). FcRn resides predominantly within the endosomal system rather than the plasma membrane, capturing ligand in acidic endosomes and routing it through Rab11-positive recycling endosomes back to the cell surface, while ligand not bound to FcRn is degraded (PMID:31444284, PMID:29523681, PMID:28817705). This salvage activity underlies serum IgG and albumin homeostasis, with hepatocyte and systemic FcRn controlling albumin levels and directional release of newly synthesized albumin (PMID:28330995), and across polarized epithelia FcRn mediates directional transcytosis, including transplacental delivery of maternal IgG (PMID:11182218, PMID:32461366). Distinct cellular roles include FcRn-dependent enhancement of neutrophil phagocytosis of IgG-opsonized bacteria, independent of recycling (PMID:16849638), and modulation of albumin catabolism that influences tumor growth and albumin-drug sensitivity (PMID:30653981, PMID:27974681). FcRn is also exploited in infection: it is hijacked by HCMV US11 for ERAD-mediated degradation (PMID:31289263) and serves as an entry/uncoating receptor for echoviruses and arteriviruses (PMID:39112502, PMID:35862785, PMID:33513208). FcRn binding is therapeutically tractable via Fc engineering that augments affinity to extend half-life (PMID:16793771) and via antagonist antibodies that occupy the IgG-binding site to lower circulating IgG (PMID:39936406). Expression is controlled transcriptionally through Sp1, AP-1, YY1, and NF-kappaB elements and post-transcriptionally by DNA methylation and miR-3181 (PMID:26252948, PMID:27555521, PMID:29302759, PMID:31209240).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1997 Medium

    Establishing where FcRn is expressed in human tissue was needed to assign physiological function; detection in intestinal epithelium implicated FcRn in mucosal IgG handling.

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

    PMID:9370926

    Open questions at the time
    • No functional transport assay in this study
    • Directionality and pH dependence of transport not addressed
  2. 1998 Medium

    Defining the cellular site of IgG salvage required localizing FcRn; endothelial cells were shown to harbor functional FcRn in intracellular vesicles consistent with serum IgG homeostasis.

    Evidence Histochemistry, immunoprecipitation, immunofluorescence in murine endothelial cells, and in vivo biodistribution

    PMID:9786428

    Open questions at the time
    • Mechanism of intracellular trafficking not resolved
    • Quantitative contribution to systemic IgG levels not measured
  3. 2000 High

    Mapping the IgG-FcRn contact at residue resolution was needed to understand pH-dependent recognition; alanine scanning defined CH2-CH3 Fc residues contacting the FcRn alpha2 domain.

    Evidence Alanine-scanning mutagenesis of IgG1 Fc with binding assays to FcRn and Fcgamma receptors

    PMID:11096108

    Open questions at the time
    • No co-crystal structure in this study
    • Membrane and avidity effects on binding not addressed
  4. 2001 Medium

    Demonstrating directional transcytosis across placental endothelium tested whether FcRn actively moves IgG; transport was time-dependent, basolateral-to-apical, and acidic-compartment dependent.

    Evidence Quantitative transcellular transport of 125I-IgG in a double-chamber system, immunofluorescence, and EM in human placental endothelial cells

    PMID:11182218

    Open questions at the time
    • Molecular trafficking machinery not identified
    • Relative contribution versus other placental cell types unresolved
  5. 2006 High

    Determining whether albumin and IgG share or use separate sites was central to FcRn's dual-ligand role; biophysics established two distinct, non-cooperative, pH-dependent binding sites with hydrophobic albumin engagement.

    Evidence SPR and isothermal titration calorimetry defining stoichiometry and thermodynamics

    PMID:16605266

    Open questions at the time
    • Albumin interface residues not yet mapped in this study
    • Structural basis of pH sensitivity not resolved here
  6. 2006 High

    Showing FcRn could act outside recycling addressed its broader immune function; granule-resident FcRn enhanced neutrophil phagocytosis of IgG-opsonized bacteria independent of IgG recycling.

    Evidence Granule fractionation, confocal microscopy, phagocytosis assays in FcRn-KO and beta2M-KO mice, and H435A IgG mutant

    PMID:16849638

    Open questions at the time
    • Molecular signaling linking FcRn to phagocytic machinery not defined
    • Generalizability to other phagocyte types not tested
  7. 2006 High

    Translating FcRn binding into half-life engineering required pH-tuned affinity variants; the YTE mutation raised acidic-pH FcRn affinity and extended serum half-life in primates.

    Evidence Fc site-directed mutagenesis, pH-defined SPR, and in vivo PK in cynomolgus monkeys

    PMID:16793771

    Open questions at the time
    • Effects of full antibody context not addressed
    • Tissue-specific distribution consequences not detailed
  8. 2014 High

    Defining the albumin-binding interface explained cross-species divergence and pH dependence; a hydrophobic surface with conserved tryptophans and a pH-sensitive loop was identified as critical.

    Evidence FcRn mutagenesis, antibody epitope-blocking, structural modelling, and SPR

    PMID:24764301

    Open questions at the time
    • No experimental co-structure of the albumin complex in this study
    • In vivo consequence of interface mutations not tested
  9. 2015 High

    Rigorous affinity determination clarified IgG-FcRn stoichiometry and species variation; two FcRn bind one IgG at symmetrical sites with defined acidic-pH affinity.

    Evidence Controlled SPR with multiple replicates and in vivo half-life in mouse and rat

    PMID:25658443

    Open questions at the time
    • Membrane-context binding not captured by cell-free SPR
    • Functional meaning of two-site avidity not resolved here
  10. 2015 Medium

    Extending FcRn cargo beyond free IgG, transcytosis of IgG-anti-IgE/IgE immune complexes was demonstrated, broadening its role in transepithelial transport.

    Evidence Transcytosis assays in FcRn-transfected MDCK cells with clinical maternal-cord correlation

    PMID:25652137

    Open questions at the time
    • Monomeric IgE not transported, mechanism of complex selectivity unresolved
    • In vivo physiological relevance not established
  11. 2017 Medium

    Quantifying the surface-versus-internal FcRn pool clarified how it captures endosomal ligand; FcRn is predominantly endosomal with a dynamically replenished surface fraction.

    Evidence Live-cell imaging, endocytosis assays, and FACS of endogenous FcRn

    PMID:28817705

    Open questions at the time
    • Sorting determinants of the endocytosis-resistant pool unknown
    • Link between pool dynamics and transport efficiency not quantified
  12. 2017 High

    Establishing FcRn's role in albumin homeostasis required genetic ablation; hepatic and global deletion caused hypoalbuminemia and biliary albumin loss, and blockade altered albumin trafficking and liver injury.

    Evidence Conditional and global knockout mice, polarized cell transcytosis, and pharmacological blockade in an APAP injury model

    PMID:28330995

    Open questions at the time
    • Cell-type contributions to systemic albumin pool not fully apportioned
    • Mechanism coupling FcRn to newly synthesized albumin secretion not detailed
  13. 2017 Medium

    Connecting albumin recycling to growth control, FcRn loss increased intracellular albumin and accelerated tumor growth, defining FcRn as a growth suppressor via nutrient handling.

    Evidence shRNA knockdown, lentiviral re-expression, xenograft growth, and intracellular amino acid measurement

    PMID:27974681

    Open questions at the time
    • Metabolic pathway linking albumin catabolism to growth not delineated
    • Single tumor model context
  14. 2018 High

    Mapping the recycling itinerary of an albumin-fusion therapeutic showed FcRn routes cargo through Rab11 recycling endosomes; the albumin moiety and FcRn were both required.

    Evidence Confocal trafficking with Rab5/Rab11/LAMP1 markers in FcRn-positive versus negative cells with fusion-defective controls

    PMID:29523681

    Open questions at the time
    • Sorting signals directing FcRn cargo to recycling versus lysosome not defined
    • Generalizability across cell types not tested
  15. 2018 Medium

    Explaining isotype differences in transport, the IgG2 lower hinge Gly236 was shown to govern transcytosis efficiency through a conformational rather than direct-contact mechanism.

    Evidence Reciprocal Fc engineering of IgG1/IgG2 with transcytosis assays in human FcRn cells

    PMID:31089170

    Open questions at the time
    • Structural basis of the conformational effect not visualized
    • In vivo PK consequences not measured
  16. 2019 High

    Defining the macrophage recycling route showed FcRn rescues albumin and monomeric IgG from macropinosomes via SNX5 domains and Rab11 endosomes, with degradation as the default fate absent FcRn.

    Evidence Primary macrophages expressing human FcRn, live imaging, fractionation, and FcRn-deficient comparison

    PMID:31444284

    Open questions at the time
    • Distinct fate of FcgammaR-bound IgG mechanistically unresolved
    • Determinants of SNX5 domain selection not defined
  17. 2019 Medium

    Linking albumin recycling to drug delivery, FcRn loss in KRAS-mutant pancreatic cells increased albumin catabolism and sensitized to albumin-conjugated doxorubicin.

    Evidence shRNA knockdown, lentiviral re-expression, proliferation assays, and xenograft models with albumin uptake measurement

    PMID:30653981

    Open questions at the time
    • Mechanism of selective DOX-ALB sensitivity not fully resolved
    • Relevance across tumor genotypes not tested
  18. 2019 High

    Revealing viral subversion of FcRn, HCMV US11 was shown to block FcRn/beta2M assembly and target FcRn for ERAD, impairing IgG transcytosis.

    Evidence Reciprocal Co-IP, siRNA knockdown of ERAD components, and transcytosis/degradation assays

    PMID:31289263

    Open questions at the time
    • In vivo consequence during natural infection not established
    • Selectivity of US11 for FcRn over other MHC-I-related molecules not detailed
  19. 2020 High

    Resolving which receptor mediates placental IgG transfer, humanized models established FcRn, not FcgammaRIIIa, as the transplacental transporter, tunable by Fc engineering.

    Evidence Humanized FcgammaR/FcRn mice, Fc-engineered IgG variants, and maternal-fetal glycan profiling

    PMID:32461366

    Open questions at the time
    • Cellular routing across the placental barrier not fully mapped
    • Glycan-dependent modulation mechanism not resolved
  20. 2020 Medium

    Extending FcRn to coagulation, monocyte FcRn was shown to amplify immune-complex-driven tissue factor/FXa activity, blockable by anti-FcRn antibody in a HIT model.

    Evidence FXa assays on monocytes with blocking antibody and Fc-mutant IgG plus a humanized murine HIT model

    PMID:32187355

    Open questions at the time
    • Signaling pathway from FcRn to tissue factor not defined
    • Single-lab in vivo model
  21. 2022 High

    Establishing FcRn as a virus uncoating receptor, cryo-EM showed FCGRT binding the echovirus 18 canyon triggers pocket-factor release, with CRISPR KO confirming requirement.

    Evidence CRISPR/Cas9 KO and cryo-EM of the E18-FcRn complex

    PMID:35862785

    Open questions at the time
    • Co-receptor requirements in physiological cells not addressed
    • Conservation of mechanism across enteroviruses not established here
  22. 2022 High

    Clarifying the membrane-context dependence of FcRn engagement, a structure plus cellular assays showed the IgG Fab impairs FcRn occupancy at the membrane but not cell-free.

    Evidence X-ray crystallography of Fc-MST-HN/FcRn, SPR, cellular binding/trafficking, and in vivo IgG reduction in monkeys

    PMID:36241613

    Open questions at the time
    • Structural detail of the membrane-restricted Fab clash not directly visualized
    • Quantitative impact on therapeutic dosing not modeled
  23. 2021 Medium

    Defining echovirus disease determinants, human FcRn alone was insufficient for infection in mice but recapitulated hepatitis when combined with type I IFN receptor deficiency.

    Evidence Transgenic hFcRn versus hFcRn-IFNAR-/- mice infected with E11, histopathology, and cytokine profiling

    PMID:33513208

    Open questions at the time
    • Molecular basis of receptor insufficiency without IFN loss unresolved
    • Tissue tropism determinants beyond FcRn not defined
  24. 2024 High

    A genome-wide screen identified FcRn as an arterivirus entry receptor acting in synergy with CD163, with blockade preventing infection.

    Evidence Genome-wide CRISPR-KO screen, gain-of-function overexpression, and anti-FcRn antibody blockade across multiple viruses and cell lines

    PMID:39112502

    Open questions at the time
    • Structural basis of FcRn-arterivirus binding not resolved
    • Mechanism of FcRn/CD163 cooperation not defined
  25. 2024 Medium

    Linking FcRn recycling to metabolic disease, adipose FcRn-driven IgG accumulation was shown to impair insulin signaling via IgG Fc-CH3 binding to the insulin receptor, reversible by FcRn targeting.

    Evidence In vivo FcRn intervention in diet-induced obesity, binding assays of IgG Fc-CH3 with insulin receptor, and adipocyte functional assays

    PMID:39674176

    Open questions at the time
    • Direct structural validation of the Fc-CH3/insulin receptor contact limited (AI-assisted)
    • Generalizability to human obesity not established
  26. 2024 Medium

    Dissecting antagonist mechanisms clarified why FcRn blockade lowers albumin, identifying both increased FcRn degradation and direct albumin-site competition across antagonist classes.

    Evidence Cellular trafficking, competition binding, and FcRn stability assays across an antagonist panel

    PMID:38713534

    Open questions at the time
    • Class-specific structural determinants of albumin competition not mapped
    • Clinical predictivity of mechanism not established
  27. 2025 High

    Defining a pH-independent antagonist mechanism, the nipocalimab Fab/FcRn structure revealed binding to the IgG site enabling sustained occupancy and selective IgG reduction.

    Evidence X-ray crystallography of the nipocalimab Fab/FcRn complex, occupancy assays, and in vivo IgG reduction in mouse and monkey

    PMID:39936406

    Open questions at the time
    • Effect on albumin homeostasis with this antagonist not detailed here
    • Long-term immune consequences not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FcRn's endosomal sorting machinery selects recycling versus degradation across diverse cell types, and how these dual IgG/albumin and immune/metabolic/infection roles are coordinated in vivo, remains unresolved.
  • Sorting determinants directing FcRn cargo to recycling versus lysosome not defined
  • Integrated structural model linking ligand binding, membrane context, and trafficking lacking
  • Tissue-by-tissue apportionment of homeostatic versus immune functions incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0001618 virus receptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005768 endosome 3 GO:0031410 cytoplasmic vesicle 3 GO:0005886 plasma membrane 2
Pathway
GO:0005215 transporter activity 3
Partners
ALBUMINB2MCD163IGGUS11
Complex memberships
FcRn-beta2-microglobulin heterodimer

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 High-resolution mapping of the IgG1 binding site on FcRn (and other Fc receptors) identified specific residues at the CH2-CH3 domain interface of IgG Fc that interact with residues primarily on the alpha2 domain of FcRn; alanine-scanning mutagenesis defined both abrogating and enhancing substitutions. Alanine-scanning mutagenesis of IgG1 Fc residues combined with binding assays to FcRn and Fc gamma receptors The Journal of biological chemistry High 11096108
2006 Introduction of the triple mutation M252Y/S254T/T256E (YTE) into the IgG1 Fc region resulted in a 10-fold increase in binding to human and cynomolgus FcRn at pH 6.0, with efficient release at pH 7.4, and produced a ~4-fold increase in serum half-life in cynomolgus monkeys and enhanced lung bioavailability. Site-directed mutagenesis of IgG Fc, surface plasmon resonance binding assays at defined pH values, in vivo pharmacokinetics in cynomolgus monkeys The Journal of biological chemistry High 16793771
2006 Albumin and IgG bind to distinct, non-overlapping sites on FcRn non-cooperatively; binding of both ligands is pH-dependent (~200-fold lower affinity for albumin at neutral vs. acidic pH); albumin binds FcRn with 1:1 stoichiometry and the interaction has hydrophobic character (large positive entropy change by ITC). Immunoblotting, surface plasmon resonance, isothermal titration calorimetry Biochemistry High 16605266
1998 FcRn is expressed in functionally active form in murine endothelial cells of small arterioles and capillaries, where it localises within intracellular vesicular structures (not on the plasma membrane), consistent with a role in maintaining serum IgG homeostasis. Histochemical analysis with anti-FcRn F(ab')2, immunoprecipitation, immunofluorescence of cultured murine endothelial cells, tissue biodistribution of FcRn-binding proteins International immunology Medium 9786428
2001 Human placental endothelial cells express functional FcRn; IgG transcytosis across these cells is time-dependent, preferentially directional (basolateral-to-apical), and IgG and FcRn co-localise in a chloroquine-sensitive intracellular endocytic compartment. Indirect immunofluorescence, RT-PCR, quantitative transcellular transport assay with 125I-labelled IgG in double-chamber system, electron microscopy with colloidal gold Human immunology Medium 11182218
2006 FcRn expressed on neutrophils resides within azurophilic and specific granules and relocates to phagolysosomes upon phagocytosis of IgG-opsonized bacteria; FcRn enhances phagocytosis in a pH-dependent, IgG recycling-independent manner, as demonstrated by impaired phagocytosis in beta2M-KO and FcRn alpha-chain-KO mice and with H435A IgG mutant that cannot bind FcRn. Subcellular fractionation/granule isolation, confocal microscopy, phagocytosis assays with FcRn-KO and beta2M-KO mice, mutant IgG (H435A), TAT-peptide inhibition Blood High 16849638
2015 Using surface plasmon resonance with rigorous artifact controls, two FcRn molecules bind an IgG homodimer at two independent, symmetrical sites with identical affinity (KD ~760 nM for human IgG1/human FcRn at pH 5.8, 25°C); affinity varies less than 2-fold with temperature and is variable across species (mouse/rat FcRn bind human IgG1 ~10-fold more tightly than human FcRn). Surface plasmon resonance with multiple experimental controls, in vivo serum half-life in mouse and rat models mAbs High 25658443
2014 Site-directed mutagenesis of human FcRn combined with blocking antibodies and structural modelling revealed that the FcRn-albumin interaction interface is predominantly hydrophobic and strictly pH-dependent, with a cluster of conserved tryptophan residues exposing a pH-sensitive loop being critical for binding; structural differences near these hotspot residues explain divergent cross-species binding properties. Site-directed mutagenesis of FcRn, monoclonal antibody blocking assays (epitope mapping), structural modelling, SPR The Journal of biological chemistry High 24764301
2017 Liver-specific or global FcRn deletion in mice causes hypoalbuminemia, biliary albumin loss, and increased intracellular hepatocyte albumin accumulation; in polarised cell models, FcRn mediates basal recycling and bidirectional transcytosis of albumin and determines physiological release of newly synthesised albumin into basal (bloodstream) milieu; FcRn blockade with antibodies or peptide mimetics recapitulates these effects and protects against APAP-induced liver injury. Conditional and global knockout mice, polarised cell transcytosis assays, pharmacological FcRn blockade with mAbs and peptide mimetics, APAP hepatotoxicity model Proceedings of the National Academy of Sciences of the United States of America High 28330995
2019 FcRn in primary macrophages mediates fast recycling of endocytosed albumin and monomeric IgG from early macropinosomes via SNX5-positive membrane domains and Rab11+ recycling endosomes to the plasma membrane; in the absence of FcRn, internalised albumin is rapidly degraded. IgG bound to surface Fcγ receptors follows a different intracellular fate. Primary mouse macrophages selectively expressing human FcRn, live-cell imaging, immunofluorescence confocal microscopy, subcellular fractionation, FcRn-deficient cell comparison Journal of cell science High 31444284
2019 Human cytomegalovirus protein US11 inhibits assembly of FcRn with β2-microglobulin, retains FcRn in the ER, and recruits ubiquitin ligase machinery (Derlin-1, TMEM129, UbE2J2) to mediate ERAD-dependent dislocation and degradation of FcRn, thereby blocking IgG transcytosis across epithelial and placental cells and enhancing IgG degradation in endothelial cells. Co-immunoprecipitation, siRNA knockdown, protein expression/localisation by immunofluorescence, transcytosis assays in transfected cell lines, IgG degradation assays Nature communications High 31289263
2020 Using humanised FcγR/FcRn mouse models and paired maternal-fetal IgG samples, only FcRn (not FcγRIIIa) mediates transplacental IgG transport; IgG variants engineered for enhanced FcRn binding showed increased fetal accumulation, while enhanced FcγRIIIa binding did not increase transport. Humanised transgenic mouse model (FcγR/FcRn), Fc-engineered IgG variants, maternal-fetal serum IgG glycan profiling, in vivo transplacental transport assay Proceedings of the National Academy of Sciences of the United States of America High 32461366
2018 The albumin fusion protein rIX-FP (recombinant factor IX–albumin) is recycled via FcRn-mediated pathway: following internalization at low pH, it traffics into early endosomes then Rab11+ recycling endosomes within 10–15 min and is exported from the cell; this pathway requires both FcRn and the albumin moiety, as fusion-defective variants and factor IX alone localise to lysosomes. Confocal microscopy with compartment markers (Rab5, Rab11, LAMP1), FcRn-expressing vs. non-expressing cell lines, fluorescently labelled protein trafficking assays The Journal of biological chemistry High 29523681
2015 FcRn mediates transcytosis of IgE across epithelial barriers in the form of IgG anti-IgE/IgE immune complexes (but not monomeric IgE); this was shown using MDCK cells stably transfected with human FcRn, where IgG anti-IgE/IgE ICs bound strongly to FcRn-expressing cells and were transcytosed in an FcRn-dependent manner. Stable transfection of MDCK cells with human FcRn, binding and transcytosis assays with IgG anti-IgE/IgE immune complexes, clinical cohort correlation of maternal and cord blood IgE/IgG IC levels Clinical and experimental allergy Medium 25652137
2017 Endogenous FcRn in cells is distributed predominantly throughout the endosomal system with only a small fraction at the plasma membrane; a significant fraction of cell-surface FcRn is endocytosis-resistant while the remainder undergoes rapid endocytosis; endocytosed FcRn is replaced from the internal pool to maintain surface levels. Live-cell fluorescence imaging, endocytosis assays, FACS analysis of surface FcRn, intracellular localisation studies PloS one Medium 28817705
2019 Loss of FcRn expression in KRAS-mutant pancreatic cancer cells reduces FcRn-mediated albumin recycling, increasing intracellular albumin catabolism and sensitizing cells to albumin-conjugated doxorubicin (DOX-ALB) but not free DOX; shRNA knockdown and lentiviral re-expression of FcRn modulated albumin recycling and drug sensitivity in vitro and in vivo. shRNA knockdown, lentiviral FcRn re-expression, cell proliferation assays, cell-derived xenograft tumor models, albumin uptake assays Journal of controlled release Medium 30653981
2017 shRNA-mediated ablation of FcRn in an FcRn-positive tumor cell line substantially increased xenograft tumor growth, while lentiviral re-expression of FcRn reduced growth; loss of FcRn increased intracellular albumin and glutamate levels, identifying FcRn as a suppressor of tumor growth through albumin recycling. shRNA knockdown, lentiviral re-expression, xenograft tumor growth assays, intracellular amino acid measurement Oncotarget Medium 27974681
2020 FcRn on monocytes augments tissue factor (TF)-dependent factor Xa (FXa) activity induced by IgG-containing immune complexes (including HIT, antiphospholipid syndrome, and anti-Rh(D) ICs); anti-FcRn monoclonal antibody blocking IgG binding to FcRn inhibited FXa induction; in a humanised murine HIT model, anti-FcRn mAb infusion prevented fibrin deposition after microvascular injury. FXa activity assays on THP-1 monocytic cells and human monocytes, anti-FcRn blocking antibody, Fc-engineered IgG unable to engage FcRn, in vivo murine HIT model with FcγRIIa transgene Blood Medium 32187355
2019 FcRn-mediated transcytosis of IgG2 across epithelial cells is reduced compared to IgG1 due to the absence of Gly236 in the IgG2 lower hinge; introduction of Gly236 into IgG2 restored transport to IgG1 levels, while deletion of Gly236 from IgG1 reduced transport to IgG2 levels; Gly236 is not a direct FcRn contact residue, suggesting a conformational mechanism. Human FcRn-expressing cell transcytosis assays, Fc-engineered IgG1/IgG2 variants with lower hinge mutations Scientific reports Medium 31089170
2022 Crystal structure of Fc-MST-HN in complex with FcRn revealed a plausible structural explanation for why the Fab region impairs FcRn binding in a membrane context: the Fab of full-length IgG impairs FcRn binding and intracellular FcRn occupancy in cellular assays (but not in cell-free assays), identifying the cellular membrane context as a critical factor in FcRn-IgG interaction. X-ray crystallography of Fc-FcRn complex, surface plasmon resonance (cell-free), cellular binding and trafficking assays (full-size IgG vs. Fc-only), IgG level reduction in cynomolgus monkeys Nature communications High 36241613
2024 FcRn is required for entry of arteriviruses into cells (identified by CRISPR-KO screen); FcRn synergises with CD163 to mediate arterivirus entry; overexpression of FcRn and CD163 sensitises non-permissive cells to infection; anti-FcRn monoclonal antibody blocked infection and rescued cells from arterivirus-induced death. Genome-wide CRISPR-KO screen, FcRn overexpression in non-permissive cells, anti-FcRn antibody blocking, viral infection assays across multiple cell lines and viral strains Nature communications High 39112502
2022 FcRn serves as a dual-function (attachment and uncoating) receptor for Echovirus 18 (E18): CRISPR/Cas9 KO of FCGRT or B2M prevented E18 infection; cryo-EM structure showed that FCGRT subunit binding to the canyon region of E18 rotates residues around the pocket factor, triggering pocket factor release (uncoating step). CRISPR/Cas9 KO screening, cryo-EM structural determination of E18-FcRn complex, viral infection assays mBio High 35862785
2021 Expression of human FcRn alone is insufficient for susceptibility to Echovirus 11 (E11) in mice; however, combined expression of human FcRn in type I IFN receptor-deficient (IFNAR-/-) mice recapitulates human echovirus pathogenesis including severe hepatitis, identifying hFcRn as the primary receptor and type I IFN signaling as a key co-determinant of echovirus disease. Transgenic mouse models (hFcRn alone vs. hFcRn-IFNAR-/-), viral infection with E11, histopathology, Luminex-based cytokine profiling PLoS pathogens Medium 33513208
1997 FcRn is expressed in human fetal and adult intestinal epithelial cells (localised to the apical region), as demonstrated by RT-PCR sequencing, Western blot, and immunohistochemistry, suggesting it mediates IgG binding in the human intestine. RT-PCR and sequencing, Western blot, immunohistochemistry of human fetal and adult intestinal tissue sections Immunology Medium 9370926
2004 The mouse Fcgrt proximal promoter contains at least two upstream regulatory regions with repressor and activator functions; transcription factor binding motifs for NF1, Sp1 (GT box), and Ets were identified; mutagenesis confirmed the GT box upregulates promoter activity in adult cells while the Ets motif represses it; differential TF binding between neonatal enterocyte and adult cell extracts was identified. Reporter gene (luciferase) assays, electrophoretic mobility shift assays (EMSA), site-directed mutagenesis Biochimica et biophysica acta Medium 15627500
2015 Within the -660/-233 fragment of the human FCGRT promoter, Sp1 sites at -641, -635, and -313, CF1/YY1 elements at -586 and -357, and AP-1 motif at -276 regulate FCGRT transcription; the Sp1 site at -313 and AP-1 at -276 are critical in epithelial and endothelial cells, while CF1/YY1 at -586 is critical in differentiated macrophage-like THP-1 cells; EMSA confirmed direct binding of Sp1, Sp2, Sp3, c-Fos, c-Jun, YY1, C/EBPbeta, and C/EBPdelta to these motifs. Site-directed mutagenesis in transient transfection reporter assays, EMSA, supershift analysis in human epithelial, endothelial, and THP-1 cell lines PloS one Medium 26252948
2016 TGEV infection of porcine intestinal epithelial cells (IPEC-J2) upregulates pFcRn expression via NF-κB signaling; NF-κB inhibitor BAY 11-7082 reduced pFcRn upregulation; NF-κB p65 overexpression enhanced pFcRn promoter luciferase activity; four NF-κB binding sites in the pFcRn promoter were confirmed by luciferase reporter, ChIP, EMSA, and supershift assays. Luciferase reporter assays, ChIP, EMSA, supershift, NF-κB inhibitor treatment, p65 overexpression Scientific reports Medium 27555521
2018 hsa-miR-3181 negatively regulates FCGRT expression by binding the 3'-UTR of FCGRT mRNA; miR-3181 mimic reduced luciferase reporter activity by 70%, decreased FCGRT mRNA by ~43–51% across three human cell lines, and decreased FcRn protein by 40%. Luciferase 3'-UTR reporter assays, microRNA mimic and inhibitor transfections, real-time RT-PCR, Western blot in A549, HEK293, and HepG2 cells Pharmaceutical research Medium 29302759
2019 DNA methylation within the -1058 to -587 bp regulatory region of FCGRT contributes to variable FcRn expression; CpG site methylation correlates with FCGRT mRNA expression in human liver and myocardium; methylation impacts binding of transcription factors Zbtb7a and Sp1 as shown by chromatin immunoprecipitation. Quantitative bisulfite DNA methylation analysis, correlation with mRNA expression in tissue samples, chromatin immunoprecipitation (ChIP), reporter assays in model cell lines Scientific reports Medium 31209240
2024 Two distinct mechanisms underlie albumin reduction during FcRn blockade: (1) increased degradation of FcRn itself (reducing salvage capacity) and (2) direct competition between certain FcRn antagonists and albumin for the same FcRn binding site; different antagonist classes vary in their relative contributions to these mechanisms. Cellular and molecular analyses of a panel of FcRn antagonists including FcRn trafficking assays, binding competition assays, FcRn protein stability measurements JCI insight Medium 38713534
2025 Crystal structure of the nipocalimab Fab/FcRn complex revealed binding to a unique epitope on the IgG-binding site of FcRn; this pH-independent binding mode supports FcRn occupancy at both neutral (extracellular) and acidic (intracellular) pH, resulting in dose/time-dependent FcRn occupancy and selective IgG reduction without effects on other immune functions. X-ray crystallography of nipocalimab Fab/FcRn complex, cell-based FcRn occupancy assays, in vivo mouse and cynomolgus monkey IgG reduction studies mAbs High 39936406
2024 FcRn-dependent recycling of IgG in adipose progenitor cells and macrophages governs IgG accumulation in adipose tissue during obesity; IgG's Fc-CH3 domain interacts with the insulin receptor's ectodomain, hindering insulin binding and obstructing insulin signaling; targeting FcRn abolished IgG accumulation and rectified insulin resistance in diet-induced obesity mice. FcRn-targeted intervention (in vivo), AI-assisted modelling, co-immunoprecipitation/binding assays of IgG Fc-CH3 with insulin receptor, in vitro adipocyte functional assays, diet-induced obesity mouse model Cell metabolism Medium 39674176
2018 FcRn is expressed in the porcine mammary gland prepartum and on the day of farrowing; the full-length porcine FcRn cDNA encodes a 359 amino acid peptide, consistent with a role for FcRn in IgG transport during colostrogenesis. RACE cloning, RT-PCR, mammary gland biopsies Veterinary immunology and immunopathology Low 12586485
2005 Human epidermal keratinocytes express functional FcRn (alpha-chain mRNA and 46 kDa protein); FcRn is distributed in granular-vesicular intracellular structures; the expressed receptor shows Fc-dependent IgG binding at acidic pH, consistent with functional activity. RT-PCR, Northern blot, real-time PCR, immunoblotting, immunoprecipitation, immunofluorescence microscopy, FACS, acid-pH IgG binding assay The Journal of investigative dermatology Medium 15654966

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 1807 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 927 11096108
2006 Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). The Journal of biological chemistry 521 16793771
2000 Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annual review of immunology 358 10837074
2019 The Neonatal Fc Receptor (FcRn): A Misnomer? Frontiers in immunology 328 31354709
1997 Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells. Immunology 251 9370926
2015 Unraveling the Interaction between FcRn and Albumin: Opportunities for Design of Albumin-Based Therapeutics. Frontiers in immunology 247 25674083
2006 Albumin binding to FcRn: distinct from the FcRn-IgG interaction. Biochemistry 224 16605266
2019 Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology 222 31118245
2013 Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Critical reviews in biotechnology 208 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 185 25703189
1997 FcRn: the MHC class I-related receptor that is more than an IgG transporter. Immunology today 166 9425738
2015 The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity. mAbs 165 25658443
2017 The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Science translational medicine 158 29093180
2006 Perspective-- FcRn transports albumin: relevance to immunology and medicine. Trends in immunology 158 16731041
2017 Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy. Frontiers in immunology 151 29163461
2019 Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. American journal of hematology 146 31821591
2001 Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells. Human immunology 146 11182218
2017 Distribution of FcRn Across Species and Tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 144 28402755
2006 FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis. Blood 142 16849638
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 122 30402880
2009 Chapter 4: Multitasking by exploitation of intracellular transport functions the many faces of FcRn. Advances in immunology 112 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 104 30130439
2014 The Role of FcRn in Antigen Presentation. Frontiers in immunology 102 25221553
2020 Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations. The Journal of allergy and clinical immunology 101 32896308
2009 Immune and non-immune functions of the (not so) neonatal Fc receptor, FcRn. Seminars in immunopathology 101 19495758
2009 FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye. Molecular vision 96 20019892
2018 Targeting FcRn to Generate Antibody-Based Therapeutics. Trends in pharmacological sciences 94 30143244
2016 Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. mAbs 92 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 91 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
2022 Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders. Frontiers in immunology 81 35757719
2015 The multiple facets of FcRn in immunity. Immunological reviews 81 26497526
2020 FcRn, but not FcγRs, drives maternal-fetal transplacental transport of human IgG antibodies. Proceedings of the National Academy of Sciences of the United States of America 80 32461366
2015 Targeting FcRn for the modulation of antibody dynamics. Molecular immunology 75 25766596
2014 FcRn: from molecular interactions to regulation of IgG pharmacokinetics and functions. Current topics in microbiology and immunology 74 25116104
2018 Expression of FcRn receptor in placental tissue and its relationship with IgG levels in term and preterm newborns. American journal of reproductive immunology (New York, N.Y. : 1989) 70 29745444
2013 Human and non-human primate intestinal FcRn expression and immunoglobulin G transcytosis. Pharmaceutical research 65 24072267
2023 FcRn inhibitors: a novel option for the treatment of myasthenia gravis. Neural regeneration research 63 36751773
2003 Sequence and expression of the FcRn in the porcine mammary gland. Veterinary immunology and immunopathology 61 12586485
2021 Programmable half-life and anti-tumour effects of bispecific T-cell engager-albumin fusions with tuned FcRn affinity. Communications biology 56 33686177
2019 KRAS-enhanced macropinocytosis and reduced FcRn-mediated recycling sensitize pancreatic cancer to albumin-conjugated drugs. Journal of controlled release : official journal of the Controlled Release Society 56 30653981
2013 Influence of FCGRT gene polymorphisms on pharmacokinetics of therapeutic antibodies. mAbs 55 23751752
2015 Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 54 25652137
2017 Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption. Oncotarget 53 27974681
2023 Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease. The Journal of clinical endocrinology and metabolism 49 37390454
2014 Neonatal Fc receptor (FcRn): a novel target for therapeutic antibodies and antibody engineering. Journal of drug targeting 48 24404896
2022 The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement. Nature communications 45 36241613
2021 IgG regulation through FcRn blocking: A novel mechanism for the treatment of myasthenia gravis. Journal of the neurological sciences 43 34563918
2017 Cell surface dynamics and cellular distribution of endogenous FcRn. PloS one 42 28817705
2021 In Translation: FcRn across the Therapeutic Spectrum. International journal of molecular sciences 39 33802650
2014 Dissection of the neonatal Fc receptor (FcRn)-albumin interface using mutagenesis and anti-FcRn albumin-blocking antibodies. The Journal of biological chemistry 39 24764301
2005 Expression of FcRn, the MHC class I-related receptor for IgG, in human keratinocytes. The Journal of investigative dermatology 39 15654966
2002 Association of bovine neonatal Fc receptor alpha-chain gene (FCGRT) haplotypes with serum IgG concentration in newborn calves. Mammalian genome : official journal of the International Mammalian Genome Society 39 12514749
2019 FcRn mediates fast recycling of endocytosed albumin and IgG from early macropinosomes in primary macrophages. Journal of cell science 37 31444284
1996 The human gene encoding the heavy chain of the major histocompatibility complex class I-like Fc receptor (FCGRT) maps to 19q13.3. Cytogenetics and cell genetics 37 8646894
1997 New functions of the MHC class I-related Fc receptor, FcRn. Biochemical Society transactions 36 9191140
2019 Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor. Nature communications 35 31289263
2012 Monoclonal antibodies directed against human FcRn and their applications. mAbs 35 22453095
2022 Effect of FcRn antagonism on protective antibodies and to vaccines in IgG-mediated autoimmune diseases pemphigus and generalised myasthenia gravis. Autoimmunity 32 36036539
2010 Association of FcRn expression with lung abnormalities and IVIG catabolism in patients with common variable immunodeficiency. Clinical immunology (Orlando, Fla.) 31 20627700
2016 TGEV infection up-regulates FcRn expression via activation of NF-κB signaling. Scientific reports 30 27555521
2020 FcRn augments induction of tissue factor activity by IgG-containing immune complexes. Blood 29 32187355
2019 Reduced FcRn-mediated transcytosis of IgG2 due to a missing Glycine in its lower hinge. Scientific reports 29 31089170
2024 FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology. Cell metabolism 28 39674176
2021 FcRn expression in cancer: Mechanistic basis and therapeutic opportunities. Journal of controlled release : official journal of the Controlled Release Society 28 34245786
2020 The neonatal Fc receptor in cancer FcRn in cancer. Cancer medicine 28 32368865
2018 Half-life-extended recombinant coagulation factor IX-albumin fusion protein is recycled via the FcRn-mediated pathway. The Journal of biological chemistry 28 29523681
2018 FcRn Expression in Wildtype Mice, Transgenic Mice, and in Human Tissues. Biomolecules 28 30326650
2021 VNTR2/VNTR3 genotype in the FCGRT gene is associated with reduced effectiveness of intravenous immunoglobulin in patients with myasthenia gravis. Therapeutic advances in neurological disorders 27 33552238
2015 Enhanced FcRn-dependent transepithelial delivery of IgG by Fc-engineering and polymerization. Journal of controlled release : official journal of the Controlled Release Society 26 26718855
2023 FcRN receptor antagonists in the management of myasthenia gravis. Frontiers in neurology 25 37602255
2021 Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice. PLoS pathogens 25 33513208
2018 Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment. Frontiers in immunology 25 30323819
2014 Application of FcRn binding assays to guide mAb development. Drug metabolism and disposition: the biological fate of chemicals 25 25024401
2024 The efficacy and safety of FcRn inhibitors in patients with myasthenia gravis: a systematic review and meta-analysis. Journal of neurology 23 38431900
2024 Efgartigimod as a novel FcRn inhibitor for autoimmune disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 23 38644454
2023 Roles of FcRn in Antigen-Presenting Cells during Autoimmunity and a Clinical Evaluation of Efgartigimod as an FcRn Blocker. Pathogens (Basel, Switzerland) 23 37375507
2023 An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission. Nature communications 23 37932271
2010 Genetic polymorphisms of FCGRT encoding FcRn in a Japanese population and their functional analysis. Drug metabolism and pharmacokinetics 21 20930418
2025 C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis. Journal of neurology, neurosurgery, and psychiatry 20 39798960
2025 Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties. mAbs 20 39936406
2024 Differential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin. JCI insight 20 38713534
2023 Therapeutic Plasma Exchange Versus FcRn Inhibition in Autoimmune Disease. Transfusion medicine reviews 20 37867088
2024 FcRn Inhibitor Therapies in Neurologic Diseases. CNS drugs 19 38724842
2022 Colostrogenesis: Role and Mechanism of the Bovine Fc Receptor of the Neonate (FcRn). Journal of mammary gland biology and neoplasia 19 35080749
2021 Prevention of diabetes-associated fibrosis: Strategies in FcRn-targeted nanosystems for oral drug delivery. Advanced drug delivery reviews 19 33887405
2021 FcRn-Targeted Mucosal Vaccination against Influenza Virus Infection. Journal of immunology (Baltimore, Md. : 1950) 19 34380652
2020 Treatment with anti-neonatal Fc receptor (FcRn) antibody ameliorates experimental epidermolysis bullosa acquisita in mice. British journal of pharmacology 19 31975370
2004 Functional analysis of the mouse Fcgrt 5' proximal promoter. Biochimica et biophysica acta 19 15627500
2024 Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study. RMD open 18 38942592
2023 IgG Fab Glycans Hinder FcRn-Mediated Placental Transport. Journal of immunology (Baltimore, Md. : 1950) 18 36480251
2021 FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review. International journal of molecular sciences 18 34204226
2019 Contribution of DNA methylation to the expression of FCGRT in human liver and myocardium. Scientific reports 18 31209240
2025 Reducing IgG accumulation via neonatal Fc receptor (FcRn) blockade relieves neuropathic pain. Brain, behavior, and immunity 17 39870199
2024 The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor. Nature communications 16 39112502
2022 Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18. mBio 16 35862785
2018 Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181. Pharmaceutical research 16 29302759
2015 Analysis of Response Elements Involved in the Regulation of the Human Neonatal Fc Receptor Gene (FCGRT). PloS one 16 26252948

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