Affinage

SERPING1

Plasma protease C1 inhibitor · UniProt P05155

Length
500 aa
Mass
55.2 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPING1 encodes C1 inhibitor (C1-INH), a serine protease inhibitor (serpin) that controls the classical and lectin complement pathways and the contact/kallikrein-kinin system by forming irreversible covalent complexes with activated C1r, C1s, MASP-1, Factor XII, and plasma kallikrein (PMID:4703226, PMID:5063623, PMID:8144914, PMID:36420270). Polyanions such as heparin and dextran sulfate accelerate C1-INH inhibition of C1s through dual interactions with both the protease and the serpin reactive center loop, while sialic acid residues on C1-INH regulate its circulatory half-life via hepatic asialoglycoprotein receptor-mediated clearance without affecting inhibitory function (PMID:19522701, PMID:7451969). Loss-of-function SERPING1 mutations cause hereditary angioedema (HAE) through distinct mechanisms including haploinsufficiency, reactive center loop cleavage converting C1-INH from inhibitor to substrate, and dominant-negative intracellular aggregation wherein mutant C1-INH traps wild-type protein in the endoplasmic reticulum (PMID:8798678, PMID:30398465, PMID:37301409, PMID:32445210). Beyond complement regulation, C1-INH promotes cortical neuronal migration upstream of C3/C5aR signaling and modulates macrophage polarization through JAK-STAT pathway suppression (PMID:28670268, PMID:37456855).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1972 Medium

    Establishing that C1-INH directly inactivates the activated C1 complex resolved the identity of the principal inhibitor of classical pathway initiation and showed the inhibition is selective for certain enzymatic activities of C1*.

    Evidence In vitro enzyme activity assays with synthetic substrates comparing heat-inactivated vs. C1-INH-inactivated C1*

    PMID:5063623

    Open questions at the time
    • Mechanism of selectivity for C2-cleaving but not C4-cleaving activity was not resolved
    • Stoichiometry of the C1-INH–C1 interaction was not determined
  2. 1973 High

    Demonstrating that C1-INH directly inhibits activated Factor XII fragments established that a single serpin controls both complement and contact/kinin pathways, explaining the dual phenotype (complement consumption and bradykinin generation) in C1-INH deficiency.

    Evidence In vitro functional inhibition assay with purified C1-INH and Hageman factor fragments, dose-response analysis

    PMID:4703226

    Open questions at the time
    • Relative physiological contribution of C1-INH vs. other Factor XII inhibitors not quantified
    • Kinetic parameters for Factor XII inhibition were not determined
  3. 1981 High

    Revealing that sialic acid residues govern C1-INH circulatory half-life via hepatic asialoglycoprotein receptors, without affecting inhibitory activity, separated the pharmacokinetic from catalytic determinants of C1-INH function.

    Evidence In vivo rabbit clearance studies with glycosidase-treated radiolabeled C1-INH; competitive inhibition with asialo-alpha1-acid glycoprotein

    PMID:7451969

    Open questions at the time
    • Role of other glycan modifications (e.g., O-glycans on the N-terminal domain) not addressed
    • Human in vivo validation not performed
  4. 1989 High

    Identifying that autoantibodies in acquired C1-INH deficiency convert C1-INH from an inhibitor to a substrate (cleavage without covalent complex formation) revealed a pathogenic mechanism distinct from genetic deficiency.

    Evidence NH2-terminal sequence analysis of patient C1-INH cleavage fragments; SDS-PAGE; functional assays

    PMID:2723058

    Open questions at the time
    • Structural basis for autoantibody-mediated substrate conversion was unknown
  5. 1994 High

    A natural C1-INH mutant that inhibits C1s but not C1r demonstrated that distinct structural determinants on C1-INH mediate inhibition of different target proteases, establishing that the serpin is not a generic inhibitor but has protease-specific recognition elements.

    Evidence Functional binding assays with activated C1s and C1r using purified patient-derived C1-INH; trypsin cleavage resistance at Arg444

    PMID:8144914

    Open questions at the time
    • Structural basis for differential C1r vs. C1s recognition not determined
    • Whether exosite interactions beyond the RCL contribute was not tested
  6. 1996 High

    Characterization of the C1INH-Ta mutant (ΔLys-251) showed that a single residue deletion converts C1-INH into a substrate for multiple proteases and causes folding abnormalities with multimerization, providing a mechanistic template for serpinopathy-type disease.

    Evidence Recombinant protein expressed in COS cells; protease complex formation assays; size fractionation; thermal stability; epitope mapping

    PMID:8798678

    Open questions at the time
    • Crystal structure of mutant conformer was not obtained
    • Whether ER quality control eliminates these misfolded species in vivo was not tested
  7. 1998 High

    Mapping autoantibody epitopes to C1-INH residues 438–459 and showing they block covalent complex formation prior to the enzyme–inhibitor encounter refined understanding of how acquired deficiency mimics the substrate-conversion mechanism seen in certain genetic mutants.

    Evidence SDS-PAGE; peptide competition assays with affinity-purified autoantibodies from two patients

    PMID:9508789

    Open questions at the time
    • Whether all acquired C1-INH deficiency autoantibodies share this epitope was not established
  8. 1997 Medium

    Detection of a C1-INH-like molecule on human and murine sperm surfaces, with antibody-mediated reduction in motility and fertilization, suggested a complement-independent reproductive function for C1-INH.

    Evidence Western blot, immunofluorescence, and ELISA on human sperm; computerized motility analysis; murine in vitro fertilization with anti-C1-INH antibody

    PMID:10607415 PMID:9412721

    Open questions at the time
    • Identity confirmation by mass spectrometry was not performed
    • Mechanism by which sperm-surface C1-INH affects motility is unknown
    • Whether this is the SERPING1 gene product or a cross-reactive protein was not genetically confirmed
  9. 2006 High

    Functional splicing assays demonstrated that specific SERPING1 splice-site mutations cause exon 2 skipping, and a common polymorphism at the exon 2 boundary contributes low-level aberrant splicing, providing a molecular explanation for variable expressivity in HAE families.

    Evidence Minigene transfection assays in HepG2/Hep3B cells; RT-PCR; family co-segregation analysis

    PMID:16470590

    Open questions at the time
    • Quantitative contribution of aberrant splicing to circulating C1-INH levels in vivo not measured
  10. 2009 High

    Using chimeric serpins, polyanion-mediated acceleration of C1s inhibition was shown to require dual interactions with both C1s and the C1-INH RCL, establishing that glycosaminoglycans serve as a template to bridge protease and inhibitor.

    Evidence In vitro association rate assays with chimeric alpha1-antitrypsin/C1-INH RCL; protease activity assays; dextran sulfate and heparin binding studies

    PMID:19522701

    Open questions at the time
    • Physiological polyanion identity in vivo (heparan sulfate vs. others) not determined
    • Structural model of the ternary complex lacking
  11. 2017 High

    In vivo knockout and knockdown of Serping1 impaired cortical neuronal migration, rescued by C3 cleavage products or C3aR/C5aR agonists, placing C1-INH upstream of complement-mediated signaling in brain development — a function unrelated to protease inhibition per se.

    Evidence In utero electroporation knockdown; Serping1 knockout mice; rescue with cleaved C3 protein or C3aR/C5aR agonist

    PMID:28670268

    Open questions at the time
    • Whether C1-INH acts by regulating complement activation or through a separate mechanism in the developing brain was not fully resolved
    • Cell-autonomous vs. non-cell-autonomous contributions not dissected at the molecular level
  12. 2018 High

    Discovery that certain HAE-causing SERPING1 mutants exert dominant-negative effects by physically interacting with wild-type C1-INH and trapping it in the ER explained why some patients have more severe disease than predicted by haploinsufficiency alone.

    Evidence Co-immunoprecipitation; immunofluorescence in patient fibroblasts; AAV gene delivery rescue

    PMID:30398465

    Open questions at the time
    • ER stress pathway involvement (UPR activation) not characterized
    • Proportion of HAE variants acting through this mechanism was unknown
  13. 2020 Medium

    Structure-function analysis of homozygous SERPING1 variants in the reactive center loop (S438F) and gate region (I379T) demonstrated region-specific mechanisms of dysfunction — substrate conversion vs. loss of protease interaction — refining genotype-phenotype correlations.

    Evidence Functional protease binding assays (C1s, FXIIa); SDS-PAGE isoform analysis; patient plasma studies

    PMID:32445210

    Open questions at the time
    • Crystal structures of gate region mutants not available
    • Only two variants characterized in detail
  14. 2023 High

    Systematic testing of 28 HAE-causing SERPING1 variants established that dominant-negative trans-inhibition of wild-type C1-INH and serpinopathy-type intracellular aggregation occur specifically in heterozygous configurations, providing a mechanistic classification framework for HAE variants.

    Evidence Transfection of HeLa cells with 28 SERPING1 variant constructs; co-expression studies measuring expression, secretion, function, and localization

    PMID:37301409

    Open questions at the time
    • In vivo validation of variant classification not performed
    • Whether therapeutic chaperones could rescue ER-retained variants not tested
  15. 2023 Medium

    Identification that C1-INH suppresses profibrotic macrophage polarization via JAK-STAT pathway downregulation extended C1-INH function beyond protease inhibition to immune cell reprogramming.

    Evidence FACS; RNA-seq; co-culture and in vivo mouse model of intrauterine adhesion

    PMID:37456855

    Open questions at the time
    • Direct molecular target of C1-INH in JAK-STAT suppression not identified
    • Whether this is protease-inhibition-dependent or independent is unknown
  16. 2024 Medium

    A novel SERPING1 variant was shown to cause ER retention that triggers GRP75-mediated calcium overload, mitochondrial damage, and apoptosis, linking C1-INH misfolding to mitochondrial pathology beyond simple loss of secretion.

    Evidence ER localization assay; GRP75 Western blot; calcium measurement; mitochondrial assays; siRNA knockdown rescue

    PMID:39272138

    Open questions at the time
    • Whether GRP75-mediated mitochondrial damage is a general feature of ER-retained C1-INH variants or specific to this mutation is unknown
    • In vivo relevance of apoptosis pathway in HAE pathology not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of C1-INH's differential protease specificity, the molecular mechanism by which C1-INH modulates JAK-STAT and mTOR signaling independent of protease inhibition, and whether therapeutic chaperones or gene therapy can rescue dominant-negative SERPING1 variants in vivo.
  • No high-resolution structure of C1-INH in complex with C1r, C1s, or MASP-1
  • Protease-independent signaling mechanisms not molecularly defined
  • In vivo rescue of dominant-negative variants not demonstrated in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 7 R-HSA-168256 Immune System 6 R-HSA-109582 Hemostasis 2 R-HSA-1266738 Developmental Biology 1
Partners
C1RC1SF12GRP75KLKB1MASP1SP5
Complex memberships
C1-INH–C1s covalent complexC1-INH–FXIIa covalent complexC1-INH–MASP-1 covalent complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1973 C1-INH (SERPING1 product) directly inhibits activated Hageman factor (Factor XII) fragments, blocking their capacity to initiate kinin generation, fibrinolysis, and coagulation. The inhibition is time-dependent and acts on the fragments themselves rather than on downstream effectors (kallikrein or plasmin). In vitro functional inhibition assay with purified C1-INH and Hageman factor fragments; dose-response analysis; gel electrophoresis The Journal of clinical investigation High 4703226
1972 C1-INH inactivates C1* (the activated C1 complex) and this inactivation is accompanied by loss of C1* activity against C2, TAMe, and ATMe synthetic substrates, without appreciably affecting activity toward C4 or AAMe, indicating that C1-INH-mediated inhibition of C1 involves an allosteric or active-site mechanism selective for certain enzymatic activities. In vitro enzyme activity assays with synthetic substrates; comparison of heat-inactivated vs. C1INH-inactivated C1* Immunology Medium 5063623
1981 Sialic acid residues on C1-INH are required for normal circulatory half-life; removal of sialic acid by neuraminidase causes rapid hepatic clearance via asialoglycoprotein receptors, while subsequent removal of galactose returns survival to near-normal. C1s inhibitory activity of C1-INH is unimpaired by desialylation, showing sialic acid regulates pharmacokinetics not catalytic function. In vivo rabbit clearance studies; glycosidase treatment; organ distribution of radiolabeled C1-INH; competitive inhibition with asialo-alpha1-acid glycoprotein Journal of immunology High 7451969
1989 In acquired C1-INH deficiency type II, anti-C1-INH autoantibodies drive cleavage of C1-INH at its active site by a target protease without formation of a covalent C1-INH–enzyme complex, generating an Mr 96,000 fragment. NH2-terminal sequence analysis confirmed this cleavage product. NH2-terminal sequence analysis of patient C1-INH fragments; functional assays of C1-INH before and after C1-INH concentrate infusion; SDS-PAGE The Journal of clinical investigation High 2723058
1994 A naturally occurring mutant C1-INH (from a kindred with incomplete C4 deficiency) inhibits C1s but not C1r, demonstrating that distinct structural determinants on C1-INH mediate inhibition of these two proteases separately. Approximately 50% of C1-INH molecules from affected members resist trypsin cleavage at Arg444. Functional binding assays with activated C1s and C1r; trypsin cleavage resistance assay; purification from patient plasma Journal of immunology High 8144914
1996 C1INH-Ta, a naturally occurring mutant with deletion of Lys-251, forms no covalent complex with C1s, C1r, or kallikrein (inefficient complex with beta-FXIIa only), and instead undergoes partial substrate cleavage by each protease. The mutation causes a folding abnormality with two populations: one susceptible to multimerization (expressing neoepitopes normally exposed only on protease-complexed C1-INH) and one converted to a substrate with residual inhibitory activity. In vitro protease complex formation assay with recombinant protein expressed in COS cells; SDS-PAGE; Superose 12 size fractionation; thermal stability analysis; epitope mapping The Journal of biological chemistry High 8798678
1998 Anti-C1-INH autoantibodies prevent formation of the stable covalent C1s–C1-INH complex by converting C1-INH to a substrate; in the presence of autoantibodies C1s cleaves C1-INH without forming a covalent bond. Autoantibodies act prior to enzyme-inhibitor complex formation and do not dissociate pre-formed complexes. The epitopes recognized map to C1-INH residues 438-459. SDS-PAGE; hydrolysis of synthetic ester substrate; affinity-purified autoantibodies from two patients; peptide competition assays Molecular medicine High 9508789
1997 A C1-INH-like molecule (C1-INH-L) is present on the surface of human sperm, anchored to the plasma membrane (trypsin-sensitive, resistant to PIPLC/EDTA/acid), localizes to head and midpiece, and is present on both uncapacitated and capacitated sperm. Anti-C1-INH antibodies reduce sperm motility and progressive velocity in the absence of complement. Western blot; ELISA; immunofluorescence; computerized sperm motion analysis with anti-C1-INH IgG treatment American journal of reproductive immunology Medium 9412721
1998 C1-INH-like protein on murine spermatozoa (MW ~100 kDa) localizes to sperm head and midpiece. Anti-C1-INH antibody treatment reduces murine sperm motility, in vitro fertilization rates, and embryo development rates, establishing a functional role for this protein in reproduction. Western blot; immunofluorescence; in vitro fertilization assay with anti-C1-INH antibody; sperm motility assay Autoimmunity Medium 10607415
2003 A deletion mutant of C1-INH lacking the N-terminal 1-99 amino acids (delta-1-99AA) is expressed on xenogeneic cell surfaces (unlike other deletion mutants which remain cytoplasmic), and this surface-bound form blocks human complement-mediated cell lysis (~57-90%) by suppressing both C4 and C3 deposition (~40% each), demonstrating that cell-surface C1-INH can inhibit complement through a distinct mechanism from DAF. Transfection of deletion mutant constructs in CHO cells and pig endothelial cells; flow cytometry for C4 and C3 deposition; complement-mediated lysis assay Xenotransplantation Medium 12588646
2009 Polyanions (dextran sulfate, heparin) bind directly to C1s and modulate its proteolytic activity biphasically (enhancement at low concentration, inhibition at higher concentration). Acceleration of the C1s–SERPING1 reaction by polyanions requires both protease-polyanion and serpin-polyanion interactions; a chimeric alpha1-antitrypsin with SERPING1 RCL residues that inhibits C1s but cannot bind polyanions showed that the DXS-mediated acceleration correlates with DXS effects on C1s activity, demonstrating that polyanion-C1s interaction contributes to the acceleration mechanism. In vitro association rate assay with chimeric serpin mutant; protease activity assays with synthetic substrates; binding studies with DXS and heparin The Biochemical journal High 19522701
2017 Knockdown or knockout of Serping1 in mice impairs neuronal stem cell proliferation and delays radial neuronal migration in the developing cortex, with both cell-autonomous and non-cell-autonomous effects. The migration defect is rescued by expression of cleaved C3 protein components or a dual C3aR/C5aR agonist, placing Serping1 upstream of complement C3 activation and C5a receptor signaling in cortical development. In utero electroporation knockdown; Serping1 knockout mice; neuronal migration assays; rescue with cleaved C3 protein or C3aR/C5aR agonist Frontiers in cellular neuroscience High 28670268
2018 A subset of HAE-causing SERPING1 variants encoded by mutant alleles exert a dominant-negative effect on wild-type C1-INH secretion by triggering protein-protein interactions between normal and mutant C1-INH, leading to intracellular aggregation and retention in the endoplasmic reticulum (ER). This ER trapping was observed in fibroblasts from a heterozygous carrier and was ameliorated by viral delivery of the SERPING1 gene. Cell transfection; co-immunoprecipitation; immunofluorescence localization; fibroblast cultures from patient; AAV gene delivery rescue experiment The Journal of clinical investigation High 30398465
2020 Serping1/C1-INH is secreted by renal tubular cells through a mitophagy-dependent mechanism; high-dose ascorbate stimulates tubular secretion of SerpinG1 via NRF2 transactivation. Secreted SerpinG1 promotes anti-inflammatory M2 macrophage polarization and prevents septic acute kidney injury. Kidney-specific SerpinG1 knockdown (AAV9-shRNA) abolishes these protective effects. FACS; RNA-sequencing; GSEA; luciferase reporter; ChIP assay; AAV9 gene knockdown in kidney-specific manner; co-culture systems; Atg7 conditional knockout mice International journal of biological sciences Medium 35982894
2022 SERPING1-encoded C1-INH forms covalent complexes with C1s (classical pathway) and MASP-1 (lectin pathway); measurement of C1s/C1-INH and MASP-1/C1-INH complexes by sandwich ELISA distinguishes early classical from early lectin pathway complement activation. Both complex levels are elevated in COVID-19 patients. Sandwich ELISA development and validation; zymosan activation of complement; clinical sample measurement in 414 COVID-19 patients and 96 healthy controls Frontiers in immunology Medium 36420270
2023 For a large set of HAE-causing SERPING1 variants (28 tested), coexpression of mutant and normal C1INH negatively affects the overall capacity to target proteases (dominant-negative trans-inhibition). A subset of variants drive intracellular C1INH foci formation only in heterozygous configurations (requiring simultaneous expression of normal and mutant C1INH), identifying distinct molecular disease mechanisms including serpinopathy-type aggregation. Transfection of HeLa cells with 28 SERPING1 variant constructs; comparative studies of C1INH expression, secretion, functionality, and intracellular localization; co-expression of wild-type and mutant constructs The Journal of allergy and clinical immunology High 37301409
2021 A missense SERPING1 mutation p.S150F produces a C1INH protein that is stably expressed intracellularly but not secreted, and when coexpressed with wild-type C1INH it prevents secretion of wild-type C1INH and promotes intracellular degradation of the wild-type protein through protein-protein interaction, demonstrating dominant-negative disease mechanism. In vitro cell transfection with mutant and wild-type constructs; secretion assay; co-expression experiments; intracellular degradation assay The Journal of dermatology Medium 33914953
2020 Homozygous SERPING1 variant S438F (in the reactive center loop) renders C1INH predominantly in the cleaved/inactive 96-kDa isoform and severely reduces C1INH interaction with target proteases C1s and FXIIa (to 4-8% of controls for FXIIa in homozygotes), while the homozygous I379T variant (in the gate region) shows near-normal heterozygous function but fails to inhibit C1s and FXIIa as a homozygote, demonstrating region-specific mechanisms of C1INH dysfunction. Functional protease binding assays measuring C1INH-C1s and C1INH-FXIIa complex formation; SDS-PAGE for isoform analysis; patient plasma studies Immunology and cell biology Medium 32445210
2024 A novel SERPING1 variant c.708T>G leads to accumulation of C1-INH in the endoplasmic reticulum, upregulation of GRP75, calcium (Ca2+) overload, mitochondrial structural and functional disruption, and apoptosis. siRNA knockdown of GRP75 mitigates the calcium overload and mitochondrial damage, placing GRP75 downstream of mutant C1-INH ER retention. Cell transfection with variant construct; ER localization assay; GRP75 Western blot; Ca2+ measurement; mitochondrial assays; siRNA knockdown of GRP75 Orphanet journal of rare diseases Medium 39272138
2006 SERPING1 splice site mutations c.51+3A>G and c.51+5G>A cause exon 2 skipping in cell transfection assays using minigene constructs. A polymorphic variant c.-21C at the second base of exon 2 also causes low but significant exon 2 skipping in transfected hepatoma cells, potentially contributing to more severe angioedema. A tissue-specific alternative splicing of exon 3 was observed in monocytes but not liver/hepatoma cells. Minigene transfection assays in HepG2 and Hep 3B cells; RT-PCR analysis; co-segregation analysis in patient family Human mutation High 16470590
2024 Glycogenolysis in postnatal astrocytes drives upregulation of Serping1 expression through reactive oxygen species (ROS)-NF-κB signaling pathway. LPS-induced astrocytic Serping1 upregulation is governed by glycogen degradation, and glycogenolysis mediates neurotoxic astrocyte phenotypes including impaired neuronal synaptogenesis. LPS treatment of postnatal hippocampal cells; glycogenolysis activation/inhibition; ROS measurement; NF-κB pathway analysis; neuronal synaptogenesis assays Molecular neurobiology Medium 38985256
2023 High levels of C1INH secreted by IL-1β/TNF-α/IFN-γ-reprogrammed mesenchymal stem cells (ITI-hUC-MSCs) prevent inflammation-induced profibrotic CD301+ macrophage polarization by downregulating the JAK-STAT signaling pathway, thereby reducing endometrial fibrosis. FACS for macrophage polarization; RNA-seq; functional co-culture assays; ITI-hUC-MSC secretome analysis; IUA mouse model iScience Medium 37456855
2018 Retinal pigment epithelium (RPE) cells upregulate C1INH expression in co-cultured bone marrow-derived macrophages, suggesting a paracrine mechanism by which RPE modulates complement regulatory expression at the retina-choroidal interface. Under inflammatory conditions (TNF-α-treated RPE), C1INH expression in macrophages is further enhanced. Co-culture of BMDMs with RPE cells/eyecups; real-time RT-PCR of complement gene expression Aging Low 29905533
2025 SP5 (WNT inhibitor/transcription factor) facilitates SERPING1 transcription by binding to the SERPING1 gene promoter. SERPING1 suppresses lung adenocarcinoma cell proliferation, migration, and invasion via the TSC2/mTOR pathway. Luciferase reporter assay; ChIP assay; in vivo and in vitro LUAD cell assays; Mendelian randomization; multi-omics Cell death & disease Medium 39962118

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1973 Inhibition by C1INH of Hagemann factor fragment activation of coagulation, fibrinolysis, and kinin generation. The Journal of clinical investigation 195 4703226
2008 Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study. Lancet (London, England) 138 18842294
2015 Hereditary angioedema with normal C1-INH with versus without specific F12 gene mutations. Allergy 106 25952149
2019 SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes. Human mutation 85 31517426
2005 Hereditary angioedema: the mutation spectrum of SERPING1/C1NH in a large Spanish cohort. Human mutation 70 15971231
2008 Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenetic and genome research 67 18758157
2016 Treatment for hereditary angioedema with normal C1-INH and specific mutations in the F12 gene (HAE-FXII). Allergy 66 27905115
1989 Acquired C1 inhibitor (C1-INH) deficiency type II. Replacement therapy with C1-INH and analysis of patients' C1-INH and anti-C1-INH autoantibodies. The Journal of clinical investigation 61 2723058
2018 Dominant-negative SERPING1 variants cause intracellular retention of C1 inhibitor in hereditary angioedema. The Journal of clinical investigation 52 30398465
2022 SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE. Frontiers in allergy 47 35958943
1981 The role of sialic acid in the functional activity and the hepatic clearance of C1-INH. Journal of immunology (Baltimore, Md. : 1950) 46 7451969
2023 Targeting endometrial inflammation in intrauterine adhesion ameliorates endometrial fibrosis by priming MSCs to secrete C1INH. iScience 44 37456855
2006 C1-inhibitor (C1-INH) autoantibodies in hereditary angioedema. Strong correlation with the severity of disease in C1-INH concentrate naïve patients. Molecular immunology 42 16750855
2013 Hereditary angioedema nationwide study in Slovenia reveals four novel mutations in SERPING1 gene. PloS one 39 23437219
2013 Hereditary angioedema with normal C1-INH (HAE type III). The journal of allergy and clinical immunology. In practice 39 24565612
2011 SERPING1 mutations in 59 families with hereditary angioedema. Molecular immunology 39 21864911
2009 Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects. Molecular vision 36 19169411
2017 Serping1/C1 Inhibitor Affects Cortical Development in a Cell Autonomous and Non-cell Autonomous Manner. Frontiers in cellular neuroscience 35 28670268
2006 Functional analysis of splicing mutations and of an exon 2 polymorphic variant of SERPING1/C1NH. Human mutation 29 16470590
1995 Complement components C1q, C1r/C1s, and C1INH in rheumatoid arthritis. Correlation of in situ hybridization and northern blot results with function and protein concentration in synovium and primary cell cultures. Arthritis and rheumatism 28 7718002
2021 Pathophysiology of Hereditary Angioedema (HAE) Beyond the SERPING1 Gene. Clinical reviews in allergy & immunology 27 33442779
2010 The effect of genetic variants in SERPING1 on the risk of neovascular age-related macular degeneration. The British journal of ophthalmology 27 20606025
2002 Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations. Human mutation 27 12402344
2022 Distinction of early complement classical and lectin pathway activation via quantification of C1s/C1-INH and MASP-1/C1-INH complexes using novel ELISAs. Frontiers in immunology 25 36420270
2020 Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation. Journal of clinical immunology 25 31982983
2020 Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients. Molecular immunology 25 32179338
2010 Exploring the HME and HAE1 efflux systems in the genus Burkholderia. BMC evolutionary biology 25 20525265
2018 Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression. Urologic oncology 24 29903461
2009 Localization of complement 1 inhibitor (C1INH/SERPING1) in human eyes with age-related macular degeneration. Experimental eye research 24 19607829
1996 Characterization of C1 inhibitor-Ta. A dysfunctional C1INH with deletion of lysine 251. The Journal of biological chemistry 24 8798678
2020 A novel deep intronic SERPING1 variant as a cause of hereditary angioedema due to C1-inhibitor deficiency. Allergology international : official journal of the Japanese Society of Allergology 23 31959500
2011 Association between the SERPING1 gene and age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese. PloS one 22 21526158
2003 Effect of various forms of the C1 esterase inhibitor (C1-INH) and DAF on complement mediated xenogeneic cell lysis. Xenotransplantation 22 12588646
2021 Hereditary angioedema due to C1 inhibitor deficiency in Belarus: epidemiology, access to diagnosis and seven novel mutations in SERPING1 gene. Clinical and molecular allergy : CMA 21 33827715
2018 Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes: The CODAM Study (Cohort on Diabetes and Atherosclerosis Maastricht)-Brief Report. Arteriosclerosis, thrombosis, and vascular biology 21 29567681
2017 2D-LC-MS/MS to measure cleaved high-molecular-weight kininogen in human plasma as a biomarker for C1-INH-HAE. Bioanalysis 21 29056074
2015 Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy. Scientific reports 21 25800435
1998 Mechanism of action of anti-C1-inhibitor autoantibodies: prevention of the formation of stable C1s-C1-inh complexes. Molecular medicine (Cambridge, Mass.) 21 9508789
2022 Tubule-mitophagic secretion of SerpinG1 reprograms macrophages to instruct anti-septic acute kidney injury efficacy of high-dose ascorbate mediated by NRF2 transactivation. International journal of biological sciences 18 35982894
2010 An association study of SERPING1 gene and age-related macular degeneration in a Han Chinese population. Molecular vision 18 20062564
2017 SERPING1 mRNA overexpression in monocytes from HIV+ patients. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 17 28889214
2010 SERPING1 polymorphisms in polypoidal choroidal vasculopathy. Molecular vision 17 20161815
2007 Association between nasal carriage of Staphylococcus aureus and the human complement cascade activator serine protease C1 inhibitor (C1INH) valine vs. methionine polymorphism at amino acid position 480. FEMS immunology and medical microbiology 17 17498209
1994 Unique C1 inhibitor dysfunction in a kindred without angioedema. I. A mutant C1 INH that inhibits C1-s but not C1-r. Journal of immunology (Baltimore, Md. : 1950) 17 8144914
1972 Fluid phase destruction of C2 hu by C1 hu. 3. Changes in activity for synthetic substrates upon cell binding, heat inactivation and interaction with C1INH. Immunology 17 5063623
2020 Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 16 33220126
2015 A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1. PloS one 16 26154504
2018 Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity. International archives of allergy and immunology 15 30278448
2016 New mutations in SERPING1 gene of Brazilian patients with hereditary angioedema. Biological chemistry 14 26812872
2022 Mutation update of SERPING1 related to hereditary angioedema in the Chinese population. Hereditas 13 35821062
2022 SerpinG1: A Novel Biomarker Associated With Poor Coronary Collateral in Patients With Stable Coronary Disease and Chronic Total Occlusion. Journal of the American Heart Association 13 36515245
2018 Hereditary angioedema due to C1-inhibitor deficiency in Macedonia: clinical characteristics, novel SERPING1 mutations and genetic factors modifying the clinical phenotype. Annals of medicine 13 29513108
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