Affinage

KLKB1

Plasma kallikrein · UniProt P03952

Round 2 corrected
Length
638 aa
Mass
71.3 kDa
Annotated
2026-04-28
73 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLKB1 encodes plasma prekallikrein, a 619-amino-acid zymogen containing four N-terminal apple domain repeats and a C-terminal trypsin-family serine protease domain that circulates bound to high-molecular-weight kininogen (HMW kininogen) and is activated by factor XIIa cleavage of a single Arg-Ile bond (PMID:3521732, PMID:291905). The resulting plasma kallikrein drives a positive-feedback amplification loop by reciprocally activating factor XII, releases bradykinin from HMW kininogen, directly cleaves complement C3 and factor B to initiate alternative-pathway complement amplification, and converts prorenin to active renin, thereby linking the contact, kinin, complement, and renin-angiotensin systems (PMID:874082, PMID:500690, PMID:29237166, PMID:26969407). Loss of KLKB1 in mice protects against arterial thrombosis through a bradykinin/Mas-receptor/prostacyclin/Sirt1/KLF4 axis that suppresses vascular tissue factor, and in vivo CRISPR editing of human KLKB1 durably reduces plasma kallikrein protein and hereditary angioedema attack frequency (PMID:25339356, PMID:38294975). Plasma kallikrein is regulated by protein C inhibitor (PCI) and TFPI-2, each with nanomolar-range inhibition constants (PMID:2844223, PMID:8555184).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1977 High

    The fundamental question of how prekallikrein becomes active on surfaces was answered: surface-bound factor XII activates prekallikrein to kallikrein in a HMW kininogen-dependent reaction, and kallikrein reciprocally activates more factor XII, establishing the positive-feedback amplification loop central to contact activation.

    Evidence Reconstitution assays with purified factor XII, prekallikrein, HMW kininogen, and kaolin surfaces

    PMID:874082

    Open questions at the time
    • Structural basis of surface-dependent activation not resolved
    • Relative contribution of each feedback cycle in vivo unknown
  2. 1979 High

    The mechanism by which prekallikrein is positioned for activation was established: prekallikrein binds HMW kininogen light chain at a single site shared with factor XI, and kallikrein cleaves HMW kininogen to liberate bradykinin while the kinin-free kininogen retains procoagulant activity.

    Evidence Quantitative binding studies with purified proteins (Ka ~3.4×10⁷ M⁻¹); SDS-PAGE and functional assays of kallikrein-cleaved kininogen

    PMID:291905 PMID:500690

    Open questions at the time
    • Atomic-resolution structure of the prekallikrein–kininogen complex not determined
    • Kinetics of bradykinin release versus coagulant activity retention not separated in vivo
  3. 1986 High

    The complete primary structure of plasma prekallikrein was determined, revealing the domain architecture (four apple domains + serine protease domain) and the precise activation cleavage site, providing the molecular framework for all subsequent structure-function studies.

    Evidence cDNA sequencing and automated Edman degradation of human prekallikrein

    PMID:3521732

    Open questions at the time
    • Three-dimensional crystal structure not yet available at this point
    • Function of individual apple domains not delineated
  4. 1988 High

    Two physiological serpin inhibitors of plasma kallikrein were characterized: protein C inhibitor (PCI) forms a 1:1 SDS-stable complex with kallikrein (k₂ ~11×10⁴ M⁻¹s⁻¹, heparin-independent), and TFPI-2 inhibits kallikrein with Ki 25 nM, identifying endogenous mechanisms that limit kallikrein activity.

    Evidence Kinetic inhibition assays and SDS-PAGE/immunoblot with purified PCI and kallikrein; amidolytic Ki determination for TFPI-2

    PMID:2551064 PMID:2844223 PMID:8555184

    Open questions at the time
    • Relative physiological importance of PCI versus C1-inhibitor versus TFPI-2 in plasma not resolved
    • In vivo contribution of each inhibitor not tested genetically
  5. 1994 High

    The cell-surface biology of contact activation was extended by demonstrating that prekallikrein, factor XI, and factor XII localize to the neutrophil exterior through HMW kininogen bridging, establishing the neutrophil as a physiological platform for contact activation.

    Evidence Immunofluorescence and peptide competition (HK31) on human neutrophils with specific antibodies

    PMID:8025275

    Open questions at the time
    • Whether neutrophil-bound prekallikrein is activated in vivo not shown
    • Identity of the neutrophil membrane receptor for kininogen not determined
  6. 2014 High

    The longstanding puzzle of whether prekallikrein deficiency affects thrombosis in vivo was resolved: Klkb1-knockout mice are protected from arterial thrombosis via a bradykinin/Mas-receptor/prostacyclin/Sirt1/KLF4 pathway that suppresses vascular tissue factor, a mechanism independent of contact-pathway coagulation.

    Evidence Klkb1⁻/⁻ mice in multiple thrombosis models with pharmacological rescue (Mas antagonist, COX-2 inhibitor, Sirt1 inhibitor)

    PMID:25339356

    Open questions at the time
    • Whether the same Mas/prostacyclin/Sirt1/KLF4 axis operates in human vasculature not confirmed
    • Contribution relative to factor XII-dependent pathway in humans unknown
  7. 2016 High

    A direct enzymatic connection between kallikrein-kinin and renin-angiotensin systems was demonstrated: kallikrein directly converts prorenin to active renin, and human genetic variants reducing kallikrein activity are associated with lower plasma renin levels.

    Evidence In vitro cleavage of recombinant prorenin; co-localization in mouse kidney; replicated genetic association in two human cohorts (n=1,180)

    PMID:26969407

    Open questions at the time
    • Cleavage site on prorenin not mapped
    • Relative contribution of kallikrein versus existing prorenin activation mechanisms not quantified
  8. 2017 High

    Kallikrein was shown to directly activate complement by cleaving C3 at the canonical convertase site and cleaving factor B, generating functional C3 convertases that feed into the alternative pathway amplification loop, establishing a direct link between contact activation and innate immune complement.

    Evidence In vitro cleavage of purified C3 and factor B by kallikrein; mass spectrometry identification of cleavage sites; functional C3 convertase assays; factor H inhibition

    PMID:29237166

    Open questions at the time
    • Physiological relevance in vivo not demonstrated genetically
    • Whether complement activation by kallikrein contributes to angioedema pathology not tested
  9. 2024 High

    Therapeutic proof of concept was achieved in humans: in vivo CRISPR-Cas9 editing of KLKB1 (NTLA-2002) produced dose-dependent, durable reductions in plasma kallikrein protein (up to −95%), confirming KLKB1 as the sole source of plasma kallikrein and demonstrating clinical benefit in hereditary angioedema.

    Evidence Phase 1 human clinical trial with LNP-delivered CRISPR-Cas9 targeting KLKB1 in liver; plasma kallikrein protein quantification

    PMID:38294975

    Open questions at the time
    • Long-term safety of complete kallikrein ablation not established
    • Effects on complement and renin pathways in treated patients not reported
  10. 2025 Medium

    A CNS-related function was proposed: KLKB1 interacts with transcription factor TFE3 and promotes neuronal ferroptosis through BRAF/MEK/ERK signaling in a vascular dementia model, extending kallikrein biology beyond hemostasis and immunity.

    Evidence Rat BCCAO model; IP-MS and Co-IP for KLKB1–TFE3 interaction; siRNA knockdown with pathway readout

    PMID:41242565

    Open questions at the time
    • Single-lab finding without independent replication
    • Mechanism by which a secreted serine protease interacts with a nuclear transcription factor is not explained
    • No reciprocal Co-IP or domain-mapping reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structural basis of the prekallikrein–kininogen complex, the in vivo hierarchy among kallikrein's multiple substrates (factor XII, kininogen, C3, factor B, prorenin), and the long-term systemic consequences of complete kallikrein elimination in humans.
  • No crystal or cryo-EM structure of prekallikrein bound to kininogen
  • Substrate selectivity determinants in vivo not mapped
  • Whether kallikrein-mediated complement activation is relevant in human disease unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3
Localization
GO:0005576 extracellular region 8 GO:0005886 plasma membrane 1
Pathway
R-HSA-109582 Hemostasis 4 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 1
Partners
C3CFBF11F12KNG1SERPINA5TFE3TFPI2
Complex memberships
prekallikrein–HMW kininogen complex

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 Human plasma prekallikrein is synthesized as a 619-amino acid single-chain zymogen (plus 19-aa signal peptide) containing four tandem apple domain repeats (each ~90-91 aa) in the heavy chain and a trypsin-family serine protease domain in the light chain; factor XIIa activates it by cleaving a single Arg-Ile bond, yielding a heavy chain (371 aa) and light chain (248 aa) held together by a disulfide bond. cDNA sequencing combined with automated Edman degradation of cyanogen bromide peptides; identification of N-glycosylation sites and activation cleavage site Biochemistry High 3521732
1977 Surface-bound Hageman factor (factor XII) activates prekallikrein to kallikrein in a reaction facilitated by high molecular weight (HMW) kininogen; the resulting kallikrein then feeds back to activate additional Hageman factor enzymatically, constituting a positive feedback amplification loop. HMW kininogen acts as a cofactor that enhances both the initial prekallikrein activation and the reciprocal kallikrein-mediated activation of Hageman factor. Reconstitution assays with purified components (HMW kininogen, prekallikrein, factor XII) and kaolin surfaces; stoichiometric analysis of cofactor interactions The Journal of clinical investigation High 874082
1979 Prekallikrein and factor XI circulate as complexes bound to HMW kininogen through its light chain, with association constants of 3.4×10⁷ M⁻¹ and 4.2×10⁸ M⁻¹, respectively; both proteins compete for a single (or closely overlapping) binding site on HMW kininogen, and this interaction is essential for HMW kininogen's coagulation cofactor activity. Direct binding studies with purified proteins; competition assays; isolated HMW kininogen light chain binding to prekallikrein and factor XI; coagulant activity assays Proceedings of the National Academy of Sciences of the United States of America High 291905
1979 Plasma kallikrein cleaves HMW kininogen to liberate bradykinin (kinin) and generate a two-chain disulfide-linked kinin-free form (heavy chain ~65 kDa, histidine-rich light chain ~44 kDa); this cleavage is dependent on prekallikrein and factor XII in plasma and the light chain retains full procoagulant activity. Purification of HMW kininogen; incubation with plasma kallikrein; SDS-PAGE; ¹²⁵I-kininogen cleavage in plasma depleted of prekallikrein or factor XII; sedimentation equilibrium The Journal of biological chemistry High 500690
1988 Protein C inhibitor (PCI) inactivates plasma kallikrein with a second-order rate constant of ~11×10⁴ M⁻¹s⁻¹ (unaffected by heparin), forming a 1:1 molar SDS-stable complex; the heavy chain of kallikrein plays a minor role in the inactivation, as PCI inhibits the isolated light chain with similar kinetics. Kinetic inhibition assays with purified PCI and plasma kallikrein; SDS-PAGE and immunoblotting of enzyme-inhibitor complexes; experiments with isolated light chains Biochemistry High 2844223
1989 PCI inhibits plasma kallikrein with a second-order rate constant of 6.50×10⁴ M⁻¹s⁻¹ (no heparin) rising to 0.18×10⁶ M⁻¹s⁻¹ with heparin; PCI does not inhibit alpha-factor XIIa or plasmin; kallikrein cleaves PCI into products of 54 kDa and 52 kDa, distinct from the 54 kDa fragment produced by most other enzymes. Kinetic inhibition studies with purified PCI; SDS-PAGE of enzyme-inhibitor complexes; comparative inhibition across multiple serine proteases Thrombosis research High 2551064
1994 Plasma prekallikrein (along with factor XI and factor XII) is present on the exterior surface of human neutrophils; prekallikrein is anchored to the neutrophil membrane through HMW kininogen, and displacement by peptide HK31 (mimicking the kininogen binding site) confirms this attachment mechanism; kinin within the membrane-bound kininogen can be released by plasma or tissue kallikrein. Immunolocalization with specific antibodies; monoclonal antibody epitope blocking; peptide competition (HK31); confocal/immunofluorescence microscopy on human neutrophils Blood High 8025275
1996 TFPI-2 (tissue factor pathway inhibitor-2) strongly inhibits human plasma kallikrein amidolytic activity with a Ki of 25 nM; heparin does not enhance this inhibition, unlike its effect on other enzymes inhibited by TFPI-2. Amidolytic inhibition assays with purified TFPI-2 and plasma kallikrein; Ki determination; heparin enhancement studies Biochemistry High 8555184
2014 Prekallikrein-null mice (Klkb1⁻/⁻) are protected from arterial thrombosis via a novel mechanism independent of contact activation: loss of bradykinin delivery to the vasculature leads to upregulation of the Mas receptor and increased prostacyclin production, which elevates aortic Sirt1 and KLF4 transcription factors and reduces vascular tissue factor (TF) mRNA, antigen, and activity. Pharmacological blockade of Mas (A-779), COX-2 (nimesulide), or Sirt1 (splitomicin) normalizes prostacyclin and restores thrombosis times; Mas agonist AVE0991 reduces thrombosis in normal mice. Genetic knockout mouse model; rose bengal and ferric chloride arterial thrombosis models; pharmacological interventions; qRT-PCR and antigen assays for TF, Mas, Sirt1, KLF4; plasma prostacyclin measurement; collagen/epinephrine pulmonary thromboembolism model Blood High 25339356
2016 Kallikrein (encoded by KLKB1) directly converts zymogen prorenin to active renin in vitro; the generated active renin cleaves angiotensinogen to angiotensin I. Kallikrein co-localizes with renin in mouse juxtaglomerular cells and kidney sections. The KLKB1 rs3733402 variant (associated with reduced plasma kallikrein activity) is associated with diminished active plasma renin levels in human cohorts, and a variant in F12 (rs1801020) reduces prekallikrein activation, further impairing this pathway. In vitro digestion of recombinant human pro-renin by kallikrein; angiotensinogen cleavage assay; immunofluorescence co-localization in mouse kidney; genetic association in two independent human cohorts (twins/siblings and US Marines, n=1,180 total); meta-analysis BMC medical genetics High 26969407
2017 Plasma kallikrein directly cleaves the complement component C3 at the same site recognized by the C3 convertase, generating active C3b and C3a; kallikrein-generated C3b forms functional C3 convertases that trigger the C3 amplification loop. Kallikrein also cleaves factor B to yield Bb and Ba, enabling kallikrein alone to drive alternative pathway complement activation. The resulting C3 convertases are inhibited by factor H, merging the kallikrein pathway with the alternative pathway amplification loop. In vitro cleavage assays with purified kallikrein and C3; mass spectrometry identification of cleavage fragments; C3b functional assays (C3 convertase formation, amplification loop); factor B cleavage assay; factor H inhibition assay; Candida albicans contact system activation in human serum Journal of innate immunity High 29237166
2024 In vivo CRISPR-Cas9 editing of KLKB1 (NTLA-2002, delivered as LNP) in humans produces dose-dependent, durable reductions in total plasma kallikrein protein (mean -67% to -95% across dose levels), demonstrating that KLKB1 is the sole source of plasma kallikrein protein and that its reduction is sufficient to markedly decrease hereditary angioedema attack frequency. Phase 1 dose-escalation clinical trial; in vivo CRISPR-Cas9 gene editing targeting KLKB1 in human liver; plasma kallikrein protein quantification; pharmacodynamic and clinical outcome assessment The New England journal of medicine High 38294975
2025 KLKB1 promotes ferroptosis in vascular dementia model rats through direct interaction with transcription factor TFE3; knockdown of KLKB1 decreases TFE3 expression and suppresses ferroptosis via inhibition of the BRAF/MEK/ERK signaling cascade. TFE3 knockdown phenocopies KLKB1 knockdown anti-ferroptotic effects. Rat bilateral common carotid artery occlusion (BCCAO) VaD model; transcriptome sequencing, GO/KEGG analysis; Western blot and qPCR; immunoprecipitation-mass spectrometry (IP-MS) to identify KLKB1 interactors; co-immunoprecipitation (Co-IP) to confirm KLKB1-TFE3 interaction; immunofluorescence; siRNA knockdown of KLKB1 and TFE3 Biochimica et biophysica acta. Molecular basis of disease Medium 41242565
2013 In mice, hepatic Klkb1 transcript levels are induced under high-fat diet conditions (paralleling F11 and Cyp4v3 induction) but are not regulated by HNF4α ablation or estrogen or thyroid hormone treatments that co-regulate F11 and Cyp4v3, indicating that within the F11-Klkb1-Cyp4v3 cluster, Klkb1 has distinct regulatory elements from F11 and Cyp4v3. Liver-specific HNF4α knockout mice; siRNA knockdown of HNF4α; estrogen and thyroid hormone treatment of mice; high-fat diet mouse model; hepatic transcript quantification by qRT-PCR PloS one Medium 24066149

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2014 An atlas of genetic influences on human blood metabolites. Nature genetics 1209 24816252
2003 Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature biotechnology 1176 12754519
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2011 Human metabolic individuality in biomedical and pharmaceutical research. Nature 801 21886157
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2012 Genome-wide association study identifies multiple loci influencing human serum metabolite levels. Nature genetics 436 22286219
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2000 Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. The Journal of biological chemistry 347 10962009
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
1986 Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein. Biochemistry 243 3636155
1977 Activation and function of human Hageman factor. The role of high molecular weight kininogen and prekallikrein. The Journal of clinical investigation 237 874082
1979 Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma. The Journal of biological chemistry 226 500690
1986 Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats. Biochemistry 214 3521732
2010 Genome-wide association of lipid-lowering response to statins in combined study populations. PloS one 190 20339536
1993 Activation of the zymogen of hepatocyte growth factor activator by thrombin. The Journal of biological chemistry 171 8226803
1996 Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous to tissue factor pathway inhibitor. Biochemistry 142 8555184
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
1988 Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry 137 2844223
2012 Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. PLoS genetics 132 22916037
2024 CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema. The New England journal of medicine 123 38294975
1994 Assembly of contact-phase factors on the surface of the human neutrophil membrane. Blood 120 8025275
1979 Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain. Proceedings of the National Academy of Sciences of the United States of America 116 291905
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2017 Kallikrein Cleaves C3 and Activates Complement. Journal of innate immunity 112 29237166
2009 Genetic variants associated with deep vein thrombosis: the F11 locus. Journal of thrombosis and haemostasis : JTH 103 19583818
1989 Purification and characterization of plasma protein C inhibitor. Thrombosis research 97 2551064
2014 Genetic determinants influencing human serum metabolome among African Americans. PLoS genetics 88 24625756
2011 Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript. Human genetics 77 21465221
2014 Reduced thrombosis in Klkb1-/- mice is mediated by increased Mas receptor, prostacyclin, Sirt1, and KLF4 and decreased tissue factor. Blood 73 25339356
2006 PSA/KLK3 AREI promoter polymorphism alters androgen receptor binding and is associated with prostate cancer susceptibility. Carcinogenesis 55 17151093
2002 Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 gives rise to novel prostate-specific proteins. The Journal of biological chemistry 50 11834722
2011 Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels. Human genetics 45 21318478
2011 Association of KLK3 (PSA) genetic variants with prostate cancer risk and PSA levels. Carcinogenesis 36 21421545
2014 The prostate cancer susceptibility variant rs2735839 near KLK3 gene is associated with aggressive prostate cancer and can stratify gleason score 7 patients. Clinical cancer research : an official journal of the American Association for Cancer Research 29 25274378
2014 KLK3, PCA3, and TMPRSS2-ERG expression in the peripheral blood mononuclear cell fraction from castration-resistant prostate cancer patients and response to docetaxel treatment. The Prostate 28 25043536
2020 Severe plasma prekallikrein deficiency: Clinical characteristics, novel KLKB1 mutations, and estimated prevalence. Journal of thrombosis and haemostasis : JTH 26 32202057
2009 A comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33. Human genetics 25 19823874
2017 Mutations in the prostate specific antigen (PSA/KLK3) correlate with male infertility. Scientific reports 24 28894123
2015 KLKB1 mRNA overexpression: A novel molecular biomarker for the diagnosis of chronic lymphocytic leukemia. Clinical biochemistry 24 25891023
2008 Development of peptides specifically modulating the activity of KLK2 and KLK3. Biological chemistry 24 18627344
2018 MRGBP promotes AR-mediated transactivation of KLK3 and TMPRSS2 via acetylation of histone H2A.Z in prostate cancer cells. Biochimica et biophysica acta. Gene regulatory mechanisms 23 30076933
2013 Genetic variation in KLK2 and KLK3 is associated with concentrations of hK2 and PSA in serum and seminal plasma in young men. Clinical chemistry 21 24270797
2007 Common variation in KLKB1 and essential hypertension risk: tagging-SNP haplotype analysis in a case-control study. Human genetics 19 17318641
2016 Polymorphisms at the F12 and KLKB1 loci have significant trait association with activation of the renin-angiotensin system. BMC medical genetics 18 26969407
2022 Accurate diagnosis of prostate cancer with CRISPR-based nucleic acid test strip by simultaneously identifying PCA3 and KLK3 genes. Biosensors & bioelectronics 15 36327902
2016 A Cross-sectional Study of KLKB1 and PRCP Polymorphisms in Patient Samples with Cardiovascular Disease. Frontiers in medicine 15 27200353
2012 Birth-and-death of KLK3 and KLK2 in primates: evolution driven by reproductive biology. Genome biology and evolution 13 23204305
2021 KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness. Scientific reports 11 33927218
2020 KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy. Prostate cancer and prostatic diseases 11 32978525
2012 Very low PSA concentrations and deletions of the KLK3 gene. Clinical chemistry 10 23169475
2011 Kallikrein-related peptidase 3 (KLK3/PSA) single nucleotide polymorphisms and ovarian cancer survival. Twin research and human genetics : the official journal of the International Society for Twin Studies 9 21787114
2020 Association of KLK3, VAMP8 and MDM4 Genetic Variants within microRNA Binding Sites with Prostate Cancer: Evidence from Serbian Population. Pathology oncology research : POR 8 32556890
2012 Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis. The Journal of urology 8 22901566
2009 Mimetics of the disulfide bridge between the N- and C-terminal cysteines of the KLK3-stimulating peptide B-2. Amino acids 8 19967419
2009 [Severe prekallikrein deficiency due to a compound heterozygosis in the KLKB1-gene]. Hamostaseologie 7 19404525
2022 KLK3 germline mutation I179T complements DNA repair genes for predicting prostate cancer progression. Prostate cancer and prostatic diseases 6 35149774
2022 Correlation analysis between CD133, Klk3 and grhl2 expression and tumor characteristics in prostate cancer. Cellular and molecular biology (Noisy-le-Grand, France) 6 35818212
2020 Association of gene polymorphisms of KLK3 and prostate cancer: A meta-analysis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 6 32869960
2017 Single-nucleotide polymorphism rs1058205 of KLK3 is associated with the risk of prostate cancer: A case-control study of Han Chinese men in Northeast China. Medicine 5 28272245
2013 Regulation of the F11, Klkb1, Cyp4v3 gene cluster in livers of metabolically challenged mice. PloS one 5 24066149
2012 Exploring the mechanism of a regulatory SNP of KLK3 by molecular dynamics simulation. Journal of biomolecular structure & dynamics 3 22877366
2025 Identifying drug targets and evaluating KLK3-targeted inhibitors for prostate cancer using in-silico and in-vitro approaches. Medical oncology (Northwood, London, England) 2 40932598
2023 Association of Kallikrein Related Peptidase 3 (KLK3) gene with dermatophytosis in the UK biobank cohort. Mycoses 2 37592324
2013 Lanthanide chelate complementation and hydrolysis enhanced luminescent chelate in real-time reverse transcription polymerase chain reaction assays for KLK3 transcripts. Analytical biochemistry 2 24084379
2025 Comparative functional analyses of the prostate-specific KLK3 enzyme in primates reveal the impact of sexual selection. Evolution; international journal of organic evolution 1 39878341
2026 Enhanced nodal staging by molecular detection of KLK3, FOLH1, and PCA3 in prostate cancer. Discover oncology 0 41843002
2025 The KLKB1-TFE3-BRAF/MEK/ERK axis regulates neuronal ferroptosis in vascular dementia. Biochimica et biophysica acta. Molecular basis of disease 0 41242565
2016 Frequency of KLK3 gene deletions in the general population. Annals of clinical biochemistry 0 27555663
2015 Association between KLKB1 Polymorphisms and Pulmonary Thromboembolism. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 0 26149136