Affinage

SERPING1

Plasma protease C1 inhibitor · UniProt P05155

Length
500 aa
Mass
55.2 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPING1 encodes C1 inhibitor (C1INH), a circulating serpin that regulates the complement, contact/coagulation, and kinin systems by inactivating their initiating proteases. C1INH selectively targets and abolishes the activity of activated C1 (C1s) against natural and synthetic substrates (PMID:5063623), neutralizes activated Hageman factor (Factor XII) fragments that drive kinin generation, fibrinolysis, and coagulation (PMID:4703226), and forms stable covalent complexes with C1s and the lectin-pathway protease MASP-1, complexes that serve as quantitative markers of classical and lectin pathway activation (PMID:36420270). Inhibition proceeds through the reactive-center loop (RCL): autoantibodies or mutations targeting RCL residues 438–459 convert C1INH into a cleaved substrate (~96 kDa) that no longer forms the inhibitory complex (PMID:9508789, PMID:32445210), and individual residues govern protease selectivity, as the Arg444 region distinguishes C1r from C1s inhibition (PMID:8144914). C1s inactivation is accelerated by polyanions (heparin, dextran sulfate) that must engage both C1INH and C1s simultaneously, a dual-cofactor bridging mechanism demonstrated with a chimeric serpin unable to bind polyanions (PMID:19522701). C1INH bears sialylated glycans required for its circulatory half-life, since desialylation triggers hepatic asialoglycoprotein-receptor clearance without affecting inhibitory activity (PMID:7451969). SERPING1 variants cause hereditary angioedema through multiple routes: loss of protease targeting from RCL or gate-region substitutions (PMID:32445210), aberrant splicing including exon skipping and deep-intronic pseudoexon activation (PMID:16470590, PMID:31982983), and a dominant-negative mechanism in which mutant C1INH heterodimerizes with wild-type protein, blocking its secretion and trapping both in ER aggregates (PMID:30398465, PMID:37301409, PMID:33914953); ER accumulation can engage GRP75, causing calcium overload, mitochondrial damage, and apoptosis (PMID:39272138). Beyond plasma protease control, Serping1 is required cell-autonomously and non-cell-autonomously for neuronal stem cell proliferation and migration upstream of C5a receptor signaling in cortical development (PMID:28670268), and secreted C1INH drives anti-inflammatory M2/JAK-STAT-dependent macrophage reprogramming in models of acute kidney injury and endometrial fibrosis (PMID:35982894, PMID:37456855).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1972 Medium

    Established that C1INH inactivates the complement protease C1s by selective active-site targeting, defining its core role as a complement regulator.

    Evidence In vitro enzymatic assays with synthetic ester and natural C4/C2 substrates comparing C1INH-mediated and heat inactivation

    PMID:5063623

    Open questions at the time
    • Does not resolve the molecular basis of selectivity at residue level
    • Single substrate-specificity inference without structural data
  2. 1973 High

    Extended C1INH's target range beyond complement to the contact system by showing it neutralizes activated Factor XII fragments controlling kinin generation, fibrinolysis, and coagulation.

    Evidence In vitro functional reconstitution with purified C1INH and Hageman factor fragments, dose-response and time-course, gel electrophoresis

    PMID:4703226

    Open questions at the time
    • Mechanism of complex stability not defined
    • Stoichiometry of inhibition not established
  3. 1981 High

    Showed that glycan sialylation, not protease activity, governs C1INH plasma persistence, separating clearance control from inhibitory function.

    Evidence In vivo rabbit pharmacokinetics with radiolabeled enzymatically desialylated C1INH, organ distribution, and asialoglycoprotein-receptor competition

    PMID:7451969

    Open questions at the time
    • Does not map specific glycosylation sites
    • Human in vivo confirmation not addressed
  4. 1994 Medium

    Demonstrated that single residues in the reactive region dictate protease selectivity, with a mutation selectively disrupting C1r but not C1s inhibition.

    Evidence Purified kindred C1INH with trypsin cleavage at Arg444, binding assays to C1s/C1r, and in vivo complement readouts

    PMID:8144914

    Open questions at the time
    • Exact causal mutation not pinpointed
    • Structural basis of differential binding not resolved
  5. 1996 High

    Mapped a folding/connecting-strand determinant (Lys-251) required for forming inhibitory complexes with C1s, C1r, and kallikrein, linking conformation to function.

    Evidence Recombinant Lys-251 deletion mutant in COS cells with complex-formation, thermal stability, size fractionation, and conformation-specific epitope assays

    PMID:8798678

    Open questions at the time
    • No high-resolution structure of the mutant
    • Mechanism of dimer formation not detailed
  6. 1998 High

    Defined the RCL (residues 438–459) as the autoantibody and cleavage target that converts C1INH from inhibitor to substrate in acquired angioedema.

    Evidence In vitro reconstitution with affinity-purified autoantibodies, peptide competition mapping, SDS-PAGE, and C1s ester-hydrolysis assays

    PMID:2723058 PMID:9508789

    Open questions at the time
    • Trigger for autoantibody production not addressed
    • Structural snapshot of substrate vs inhibitor pathway absent
  7. 2009 High

    Resolved the cofactor mechanism of polyanion acceleration, showing heparin/dextran sulfate must bridge both C1INH and C1s to enhance inhibition.

    Evidence Enzyme kinetics, association-rate measurements, and a chimeric alpha1-antitrypsin/SERPING1-RCL serpin unable to bind polyanions

    PMID:19522701

    Open questions at the time
    • Physiological polyanion in vivo not identified
    • Ternary complex structure not determined
  8. 2006 Medium

    Clarified how SERPING1 mutations affect mRNA, establishing exon-2 skipping splicing defects (including a modifier polymorphism) as a pathogenic and severity-modifying mechanism.

    Evidence Minigene transfection in hepatoma cells, RT-PCR, cell-type-specific splicing analysis, and family co-segregation

    PMID:16470590

    Open questions at the time
    • Quantitative contribution of modifier allele to phenotype not fully resolved
    • Single laboratory
  9. 2020 Medium

    Connected variant location to functional consequence, showing RCL (S438F) and gate-region (I379T) substitutions abolish or reduce protease inhibition with dosage- and severity-dependent effects.

    Evidence Plasma C1INH functional complex-formation assays with C1s and FXIIa, isoform SDS-PAGE, and clinical correlation in consanguineous families

    PMID:32445210

    Open questions at the time
    • Mechanism of partial inhibition for gate variant not structurally explained
    • Limited to specific consanguineous families
  10. 2020 Medium

    Added deep-intronic pseudoexon activation as a previously unrecognized pathogenic SERPING1 mechanism in hereditary angioedema.

    Evidence NGS/Sanger sequencing with RT-PCR validation of aberrant transcript from patient blood RNA

    PMID:31982983

    Open questions at the time
    • Prevalence of pseudoexon mechanism unknown
    • Protein-level consequence not directly assayed
  11. 2018 High

    Established a dominant-negative disease mechanism in which mutant C1INH physically interacts with wild-type protein, causing joint ER retention and aggregation in patient cells.

    Evidence Co-immunoprecipitation, confocal ER colocalization in heterozygous patient fibroblasts, and lentiviral gene-delivery rescue

    PMID:30398465

    Open questions at the time
    • Structural basis of heteroaggregation undefined
    • Not all dominant-negative variants share one aggregation route
  12. 2021 Medium

    Provided single-variant evidence that mutant C1INH (p.S150F) traps and drives cytoplasmic degradation of co-expressed wild-type protein, refining the dominant-negative secretion-blocking model.

    Evidence Cotransfection of mutant and wild-type constructs with Western blot for intracellular vs secreted C1INH and interaction/degradation assays

    PMID:33914953

    Open questions at the time
    • Single variant, single laboratory
    • Degradation pathway not molecularly identified
  13. 2023 High

    Systematically generalized the dominant-negative mechanism across variants, showing most disease alleles reduce protease targeting in coexpression and that ER foci form only in heterozygous configurations.

    Evidence HeLa transfection of 28 SERPING1 variants with parallel readouts of expression, secretion, protease targeting, and intracellular foci imaging

    PMID:37301409

    Open questions at the time
    • Quantitative correlation to clinical severity incomplete
    • Cellular machinery sensing heterocomplexes not identified
  14. 2022 Medium

    Linked ER-retained C1INH to downstream organelle toxicity, identifying GRP75-dependent calcium overload, mitochondrial damage, and apoptosis as consequences of a misfolding variant.

    Evidence Patient-derived cell analysis with ER colocalization, GRP75 quantification, Ca2+ and mitochondrial readouts, and siRNA-GRP75 rescue

    PMID:39272138

    Open questions at the time
    • Generality across other ER-retained variants untested
    • Single laboratory
  15. 2022 Medium

    Validated C1s/C1INH and MASP-1/C1INH covalent complexes as quantitative, pathway-specific biomarkers of classical and lectin pathway activation.

    Evidence Sandwich ELISA development, zymosan activation controls, and a clinical COVID-19 cohort

    PMID:36420270

    Open questions at the time
    • Does not establish causal disease contribution
    • Pathway crosstalk not dissected
  16. 2017 Medium

    Expanded C1INH biology beyond plasma protease control, placing it in cortical development upstream of complement C5a receptor signaling for neural progenitor proliferation and migration.

    Evidence In utero electroporation knockdown and Serping1 knockout mice with cleaved-C3 and C3aR/C5aR agonist rescue of migration defects

    PMID:28670268

    Open questions at the time
    • Molecular link between C1INH and C5a signaling not defined
    • Human relevance untested
  17. 2023 Medium

    Identified a secreted, anti-inflammatory function for C1INH in driving macrophage reprogramming via JAK-STAT downregulation across tissue-injury models.

    Evidence Co-culture, FACS macrophage polarization, JAK-STAT readouts, and C1INH neutralization in kidney-injury and intrauterine-adhesion mouse models with AAV9-shRNA knockdown

    PMID:35982894 PMID:37456855

    Open questions at the time
    • Receptor mediating macrophage effect unidentified
    • Relationship to canonical protease-inhibitor activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the protease-inhibitor activity of C1INH mechanistically relates to its non-canonical roles in neurodevelopment and macrophage polarization, and the receptors or signaling intermediates involved, remains unresolved.
  • No receptor identified for extracellular C1INH signaling
  • No structural model integrating RCL inhibition with non-canonical functions
  • Causal molecular link to C5a receptor and JAK-STAT pathways undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0140313 molecular sequestering activity 4
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005576 extracellular region 3
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-109582 Hemostasis 1
Partners
C1RC1SF12MASP1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1973 Purified C1INH inhibits activated Hageman factor (Factor XII) fragments from initiating kinin generation, fibrinolysis, and coagulation in a dose-dependent, time-dependent manner; the fragments could no longer be recovered functionally or by gel electrophoresis after interaction with C1INH, suggesting an enzymatic or additional inhibitory mechanism. In vitro functional assay with highly purified C1INH and Hageman factor fragments; dose-response and time-course analysis; alkaline disc gel electrophoresis The Journal of clinical investigation High 4703226
1972 C1INH inactivates C1 (C1s component) as shown by loss of activity against synthetic substrates (TAMe, ATMe) and natural substrates C2 upon heat inactivation or C1INH treatment, without appreciably affecting C4 hydrolysis or AAMe cleavage, indicating selective active-site targeting. In vitro enzymatic assay with synthetic ester substrates (AGLMe, AAMe, TAMe, ATMe) and natural substrates C4/C2; comparison of heat inactivation vs C1INH-mediated inactivation Immunology Medium 5063623
1981 Sialic acid residues on C1INH are required for normal circulatory half-life: removal of sialic acid by neuraminidase causes rapid hepatic clearance via asialoglycoprotein receptors, while subsequent removal of penultimate galactose restores near-normal survival; C1s inhibitory activity is unimpaired by desialylation. In vivo rabbit studies with radiolabeled C1INH treated with immobilized neuraminidase and beta-galactosidase; organ distribution; competition with asialo alpha1-acid glycoprotein; immunochemical and functional assays Journal of immunology High 7451969
1989 In acquired C1-INH deficiency type II, anti-C1-INH autoantibodies recognize epitopes within C1-INH and promote cleavage of C1-INH at its active site without generation of a covalent C1-INH–enzyme complex, producing a 96 kDa fragment; the resulting fragment is consistent with protease cleavage of C1-INH without stable inhibitory complex formation. NH2-terminal sequence analysis; replacement therapy with C1-INH concentrate in patients; SDS-PAGE analysis of C1-INH fragments; functional complement assays (CH50, C4, C1 hemolytic activity) The Journal of clinical investigation Medium 2723058
1994 A naturally occurring mutant C1INH in a kindred inhibits C1s but not C1r; approximately 50% of molecules in the preparation resist cleavage by trypsin at Arg444, indicating a mutation affecting this region that selectively disrupts C1r inhibition while preserving C1s inhibition in vivo. Purification of C1INH from affected kindred plasma; trypsin cleavage assay; binding assay to activated C1s and C1r; C2 levels and C4 catabolism as in vivo functional readouts Journal of immunology Medium 8144914
1996 Deletion of Lys-251 in C1INH-Ta (located in the connecting strand between helix F and strand 3A) abolishes complex formation with C1s, C1r, and kallikrein while retaining residual inhibitory activity with beta-factor XIIa; the mutant shows intermediate thermal stability and forms dimers with epitopes normally exposed only upon protease complexing or cleavage, indicating a folding abnormality consistent with two populations of molecules. Recombinant protein expression in COS cells; SDS-PAGE and Superose 12 size fractionation; protease complex formation assays; thermal stability; epitope analysis with conformation-specific antibodies The Journal of biological chemistry High 8798678
1998 Anti-C1-INH autoantibodies from acquired angioedema patients prevent formation of the stable covalent C1s-C1-INH complex by binding to epitopes corresponding to C1-INH residues 438–459 (reactive center loop region), thereby converting C1-INH into a substrate that is cleaved by C1s without forming the inhibitory complex; preformed C1s-C1-INH complexes are not dissociated by the autoantibodies. SDS-PAGE; synthetic ester hydrolysis assay for C1s activity; affinity-purified autoantibodies; peptide competition assays with synthetic C1-INH peptides (residues 428-440, 438-449, 448-459) Molecular medicine High 9508789
1997 A C1-INH-like molecule (C1-INH-L) is present on the surface of human sperm (head and midpiece), is trypsin-sensitive but resistant to PIPLC, EDTA, and acid treatment, and is present on both uncapacitated and capacitated sperm; antibodies to C1-INH reduce sperm motility and progressive velocity in the absence of complement, suggesting a complement-independent role in sperm motility. Western blot; ELISA; immunofluorescence; computerized sperm motion analysis with anti-C1-INH IgG treatment American journal of reproductive immunology Low 9412721
2003 A surface-bound deletion mutant of C1-INH (delta-1-99 AA, lacking the N-terminal 99 amino acids) expressed on xenogeneic cell surfaces blocks human complement-mediated cell lysis (~57–90% inhibition) and reduces C4 and C3 deposition (~40% suppression), whereas other C1-INH deletion mutants lacking loop or exon regions are expressed only in the cytoplasm and not on the cell surface. cDNA transfection of deletion mutants into CHO cells and pig endothelial cells; flow cytometry for surface expression and C4/C3 deposition; complement-mediated lysis assay Xenotransplantation Medium 12588646
2006 Splicing mutations at positions +3 and +5 of intron 2 of SERPING1 result in exon 2 skipping in cell transfection assays; the c.51+3A>G mutation co-segregates with low C1INH levels. A polymorphic variant at the second base of exon 2 (c.-21C allele) causes low but significant levels of exon 2 skipping in HepG2/Hep3B hepatoma cells, potentially contributing to more severe angioedema. An alternative splicing of exon 3 was detected in peripheral blood mononuclear cells but not liver, and mutations affecting exon 2 splicing shift this to skipping of both exons 2 and 3 in monocytes. Minigene transfection assays in hepatoma cells; RT-PCR; family co-segregation analysis; cell-type-specific splicing analysis in monocytes Human mutation Medium 16470590
2009 Polyanions (dextran sulfate, heparin) bind to C1s and modulate its proteolytic activity in a biphasic manner (enhancement at low concentrations, inhibition at high concentrations); acceleration of SERPING1-mediated C1s inactivation by polyanions requires interactions with both SERPING1 and C1s, as demonstrated using a chimeric alpha1-antitrypsin mutant carrying SERPING1 reactive-center loop residues that inhibits C1s but cannot bind polyanions. Biochemical binding assays; enzyme kinetics; chimeric serpin construction and functional assay; association rate measurements The Biochemical journal High 19522701
2017 Knockdown or knockout of Serping1 in mice impairs neuronal stem cell proliferation and delays neuronal migration in a cell-autonomous and non-cell-autonomous manner; expression of cleaved C3 protein rescued Serping1 knockdown-mediated migration defects, and a dual C3aR/C5aR agonist (but not C3aR agonist alone) significantly rescued the phenotype, placing Serping1 upstream of C5a receptor signaling in cortical development. In utero electroporation knockdown; Serping1 knockout mice; rescue with cleaved C3 protein expression; pharmacological receptor agonist rescue; neuronal migration assay Frontiers in cellular neuroscience Medium 28670268
2018 A subset of HAE-causing SERPING1 alleles encode C1INH variants that act in a dominant-negative fashion by forming protein-protein interactions with normal C1INH, creating larger intracellular aggregates that are retained in the endoplasmic reticulum; ER trapping was directly observed in fibroblasts from heterozygous HAE type I patients carrying dominant-negative variants, and was ameliorated by viral SERPING1 gene delivery. Co-immunoprecipitation; cell transfection with mutant and wild-type SERPING1 constructs; confocal microscopy (ER colocalization); patient fibroblast analysis; lentiviral gene delivery rescue The Journal of clinical investigation High 30398465
2020 A deep intronic mutation (c.1029+384A>G) in intron 6 of SERPING1 creates a de novo donor splice site, activating a pseudoexon insertion into the mRNA, establishing pseudoexon activation as a novel pathogenic mechanism for SERPING1/HAE. Next-generation sequencing; Sanger sequencing; RT-PCR to detect aberrant transcripts; in silico splice site analysis; mRNA analysis from patient blood-derived RNA Journal of clinical immunology Medium 31982983
2022 C1s forms covalent complexes with C1-INH (C1s/C1-INH) as a marker of classical pathway activation; MASP-1 similarly forms complexes with C1-INH (MASP-1/C1-INH) as a marker of lectin pathway activation. These complexes are quantifiable by sandwich ELISA, are increased by zymosan activation, and are elevated in COVID-19 patients, validating them as pathway-specific markers. Sandwich ELISA development and validation; zymosan activation assay; clinical cohort measurement (414 COVID-19 patients, 96 controls) Frontiers in immunology Medium 36420270
2022 Novel SERPING1 variant c.708T>G causes accumulation of C1-INH in the endoplasmic reticulum, leading to upregulation of GRP75, Ca2+ overload, disruption of mitochondrial structure and function, and apoptosis; siRNA knockdown of GRP75 mitigates calcium overload and mitochondrial damage caused by this mutation. Patient-derived cell analysis; immunofluorescence (ER colocalization); GRP75 protein quantification; Ca2+ measurement; mitochondrial structural analysis; siRNA knockdown rescue Orphanet journal of rare diseases Medium 39272138
2023 For 26 of 28 disease-associated SERPING1 variants tested, coexpression of mutant and normal C1INH negatively affected the overall capacity to target proteases (dominant-negative effect); a subset of variants induced intracellular C1INH foci detectable only in heterozygous configurations, demonstrating that dominant-negative ER aggregation requires simultaneous presence of both wild-type and mutant C1INH. HeLa cell transfection with 28 SERPING1 variant expression constructs; comparative analysis of C1INH expression, secretion, functionality (protease targeting), and intracellular localization; immunofluorescence for foci The Journal of allergy and clinical immunology High 37301409
2021 A missense SERPING1 mutation p.S150F produces a stably expressed C1INH that is not secreted and prevents secretion of co-expressed wild-type C1INH, with the wild-type protein degraded within the cytoplasm through interaction with the mutant protein, demonstrating a dominant-negative secretion-blocking mechanism. In vitro cell transfection (cotransfection of mutant and wild-type constructs); Western blot for intracellular vs secreted C1INH; protein interaction/degradation assays The Journal of dermatology Medium 33914953
2020 Homozygous SERPING1 variant S438F (in the reactive center loop region) abolishes C1INH interaction with C1s and FXIIa in a dose-dependent manner, leaving only the cleaved/inactive 96 kDa isoform in homozygous carriers; the gate-region variant I379T produces normal C1INH/C1s binding in heterozygotes but markedly reduced inhibition in homozygotes, correlating with clinical severity. Plasma C1INH functional assays (C1s and FXIIa complex formation); SDS-PAGE protein isoform analysis; complement measurements (C4, C1q); clinical correlation in consanguineous families Immunology and cell biology Medium 32445210
2022 High-dose ascorbate stimulates tubular renal epithelial cells to secrete SerpinG1 (C1INH) through mitophagy maintenance, and this secreted SerpinG1 promotes anti-inflammatory M2 macrophage polarization by downregulating JAK-STAT signaling, thereby reducing septic acute kidney injury; kidney-specific AAV9-shRNA disruption of SerpinG1 abrogated the anti-inflammatory macrophage polarization and protective effect. Co-culture systems; FACS analysis of macrophage polarization; RNA-sequencing; GSEA; luciferase reporter; ChIP assay; AAV9-shRNA in vivo delivery; LPS-induced endotoxemia mouse model with tubular Atg7 knockout International journal of biological sciences Medium 35982894
2023 C1INH secreted by IL-1β/TNF-α/IFN-γ-primed mesenchymal stem cells prevents inflammation-induced profibrotic CD301+ macrophage polarization by downregulating the JAK-STAT signaling pathway, thereby reducing endometrial fibrosis in an intrauterine adhesion mouse model. IUA mouse model; MSC co-culture; FACS for macrophage polarization markers; JAK-STAT pathway inhibition assay; C1INH neutralization iScience Medium 37456855
2009 C1INH protein is localized to photoreceptor cells, inner nuclear layer neurons, choriocapillaris, and choroidal extracellular matrix in human donor eyes by immunofluorescence; AMD-affected eyes showed increased abundance of choroidal C1INH, implicating local classical/lectin pathway complement regulation at the retina-choroidal interface. Immunofluorescence with monoclonal anti-C1INH antibody; Western blot; genotype-stratified analysis Experimental eye research Low 19607829
2018 RPE cells upregulate C1INH expression in bone marrow-derived macrophages when co-cultured, suggesting RPE-mediated regulation of macrophage complement inhibitor expression at the retina-choroidal interface; TNF-α-pretreated RPE further enhanced C1INH expression in macrophages. Co-culture of BMDMs with RPE cells and RPE-choroid eyecups; real-time RT-PCR for complement gene expression Aging Low 29905533
1995 Synovial tissue in rheumatoid arthritis synthesizes and secretes C1INH de novo; in situ hybridization identifies the synovial lining cell layer as the site of C1INH expression, while macrophages within primary cell cultures express C1q and fibroblasts express C1r. Northern blotting; in situ hybridization; pulse-chase experiments; antigenic and functional analysis of primary synovial cell cultures from RA patients Arthritis and rheumatism Medium 7718002

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 196 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 108 25952149
2019 SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes. Human mutation 88 31517426
2005 Hereditary angioedema: the mutation spectrum of SERPING1/C1NH in a large Spanish cohort. Human mutation 71 15971231
2008 Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenetic and genome research 68 18758157
2016 Treatment for hereditary angioedema with normal C1-INH and specific mutations in the F12 gene (HAE-FXII). Allergy 67 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
2022 SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE. Frontiers in allergy 54 35958943
2018 Dominant-negative SERPING1 variants cause intracellular retention of C1 inhibitor in hereditary angioedema. The Journal of clinical investigation 53 30398465
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 45 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 41 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
2021 Pathophysiology of Hereditary Angioedema (HAE) Beyond the SERPING1 Gene. Clinical reviews in allergy & immunology 29 33442779
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
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 27 36420270
2020 Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients. Molecular immunology 27 32179338
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
2020 Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation. Journal of clinical immunology 25 31982983
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
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 22 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 22 29567681
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
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
2017 SERPING1 mRNA overexpression in monocytes from HIV+ patients. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 18 28889214
2010 An association study of SERPING1 gene and age-related macular degeneration in a Han Chinese population. Molecular vision 18 20062564
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 17 33220126
2015 A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1. PloS one 17 26154504
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
2018 Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity. International archives of allergy and immunology 16 30278448
2016 New mutations in SERPING1 gene of Brazilian patients with hereditary angioedema. Biological chemistry 15 26812872
2022 Mutation update of SERPING1 related to hereditary angioedema in the Chinese population. Hereditas 14 35821062
2023 Combined anti-C1-INH and radiotherapy against glioblastoma. BMC cancer 13 36717781
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
2009 Modulation of the proteolytic activity of the complement protease C1s by polyanions: implications for polyanion-mediated acceleration of interaction between C1s and SERPING1. The Biochemical journal 13 19522701
2022 Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus Nephritis. International journal of molecular sciences 12 36012546
2018 The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells - implication in subretinal immune privilege in the aging eye. Aging 12 29905533
2013 Cloning and molecular characterization of complement component 1 inhibitor (C1INH) and complement component 8β (C8β) in Nile tilapia (Oreochromis niloticus). Fish & shellfish immunology 12 23876999
2013 Identification and characterization of a novel splice site mutation in the SERPING1 gene in a family with hereditary angioedema. Clinical immunology (Orlando, Fla.) 12 24412907
2020 Hereditary angioedema in a single family with specific mutations in both plasminogen and SERPING1 genes. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 11 32065705
2017 Mutational spectrum of the SERPING1 gene in Swiss patients with hereditary angioedema. Clinical and experimental immunology 11 28194776
2015 Recombinant human C1 esterase inhibitor for the treatment of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE). Expert review of clinical immunology 11 25669442
2014 A novel splice site mutation in the SERPING1 gene leads to haploinsufficiency by complete degradation of the mutant allele mRNA in a case of familial hereditary angioedema. Journal of clinical immunology 11 24760113
2020 Association of increase in Serping1 level with dopaminergic cell reduction in an MPTP-induced Parkinson's disease mouse model. Brain research bulletin 10 32485229
1989 FN-C1q and C1 INH C1r-C1s complexes as indicators of complement activation in patients with chronic lymphocytic leukaemia. Immunology letters 10 2550362
2023 Restriction of C1-inhibitor activity in hereditary angioedema by dominant-negative effects of disease-associated SERPING1 gene variants. The Journal of allergy and clinical immunology 9 37301409
2023 Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)-A Bicenter Retrospective Study on Diagnosis, Course, and Therapy. The journal of allergy and clinical immunology. In practice 9 37716525
2021 In Search of an Association Between Genotype and Phenotype in Hereditary Angioedema due to C1-INH Deficiency. Clinical reviews in allergy & immunology 9 33469833
2019 SERPING1 exon 3 splicing variants using alternative acceptor splice sites. Molecular immunology 9 30685616
2019 Serum complexes between C1INH and C1INH autoantibodies for the diagnosis of acquired angioedema. Clinical and experimental immunology 9 31397881
2017 Effect of C1-INH on ischemia/reperfusion injury in a porcine limb ex vivo perfusion model. Molecular immunology 9 28641140
2022 Overview of SERPING1 Variations Identified in Hungarian Patients With Hereditary Angioedema. Frontiers in allergy 8 35386643
2018 Gene mapping strategy for Alu elements rearrangements: Detection of new large deletions in the SERPING1 gene causing hereditary angioedema in Brazilian families. Gene 8 30389558
2013 Identification of a novel and recurrent mutation in the SERPING1 gene in patients with hereditary angioedema. Clinical immunology (Orlando, Fla.) 8 23583915
2011 New therapeutics in C1INH deficiency: a review of recent studies and advances. Current allergy and asthma reports 8 21607669
2011 Analysis of SERPING1 expression on hereditary angioedema patients: quantitative analysis of full-length and exon 3 splicing variants. Immunology letters 8 22001489
2002 C1r-C1s-C1inhibitor (C1rs-C1inh) complex measurements in tears of patients before and after penetrating keratoplasty. Current eye research 8 12187480
2021 Evidence for a dominant-negative effect of a missense mutation in the SERPING1 gene responsible for hereditary angioedema type I. The Journal of dermatology 7 33914953
2020 Genetic variants of SERPING1 gene in Polish patients with hereditary angioedema due to C1 inhibitor deficiency. Central-European journal of immunology 7 33437182
2014 Stability of murine bradykinin type 2 receptor despite treatment with NO, bradykinin, icatibant, or C1-INH. Allergy 7 25477154
2006 Haploinsufficiency due to deletion within the 3'-UTR of C1-INH-gene associated with hereditary angioedema. Genetics in medicine : official journal of the American College of Medical Genetics 7 16617246
1997 The presence of a C1-inhibitor-like molecule (C1-INH-L) on human sperm: its involvement in sperm motility. American journal of reproductive immunology (New York, N.Y. : 1989) 7 9412721
1991 C1-INH defect as an example of deficiency disease. Immunological investigations 7 1864632
2024 Complex analysis of the national Hereditary angioedema cohort in Slovakia - Identification of 12 novel variants in SERPING1 gene. The World Allergy Organization journal 6 38486718
2024 Uncovering a novel SERPING1 pathogenic variant: insights into the aggregation of C1-INH in hereditary angioedema. Orphanet journal of rare diseases 6 39272138
2022 Searching for Genetic Biomarkers for Hereditary Angioedema Due to C1-Inhibitor Deficiency (C1-INH-HAE). Frontiers in allergy 6 35873600
2019 Identification and Mapping of a 2,009-bp DNA Deletion in SERPING1 of a Hereditary Angioedema Patient. Case reports in genetics 6 30923640
2017 A Case of Type 2 Hereditary Angioedema With SERPING1 Mutation. Allergy, asthma & immunology research 6 27826968
2024 HME, NFE, and HAE-1 efflux pumps in Gram-negative bacteria: a comprehensive phylogenetic and ecological approach. ISME communications 5 38371394
2023 Effects of C1-INH Treatment on Neurobehavioral Sequelae and Late Seizures After Traumatic Brain Injury in a Mouse Model of Controlled Cortical Impact. Neurotrauma reports 5 36941878
2023 The Effects of Serping1 siRNA in α-Synuclein Regulation in MPTP-Induced Parkinson's Disease. Biomedicines 5 37509591
2020 Novel homozygous variants in the SERPING1 gene in two Turkish families with hereditary angioedema of recessive inheritance. Immunology and cell biology 5 32445210
2020 Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene. Clinical and translational allergy 5 33292549
2019 A hereditary angioedema screening in two villages, based on an index case, and identification of a novel mutation, "1033G>T", at the SERPING1 gene. Postepy dermatologii i alergologii 5 31616213
2014 Expression of the SERPING1 gene is not regulated by promoter hypermethylation in peripheral blood mononuclear cells from patients with hereditary angioedema due to C1-inhibitor deficiency. Orphanet journal of rare diseases 5 25053016
2024 Glycogenolysis-Induced Astrocytic Serping1 Expression Regulates Neuroinflammatory Effects on Hippocampal neuron. Molecular neurobiology 4 38985256
2018 First Analysis of SERPING1 Gene in Patients with Hereditary Angioedema in Colombia Reveals Two Genotypic Variants in a Highly Symptomatic Individual. Journal of clinical immunology 4 29623547
1998 Complement component 1 inhibitor (C1-INH) like protein on murine spermatozoa: anti-C1-INH inhibits in vitro fertilization. Autoimmunity 4 10607415
2025 WNT inhibitor SP5-mediated SERPING1 suppresses lung adenocarcinoma progression via TSC2/mTOR pathway. Cell death & disease 3 39962118
2024 Elevated C1s/C1-INH in serum and plasma of myasthenia gravis patients. Journal of neuroimmunology 3 39255718
2012 A novel mutation in exon 8 of C1 inhibitor (C1INH) gene leads to abolish its physiological stop codon in a large Chinese family with hereditary angioedema type I. Experimental dermatology 3 22882460

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