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Protein / target

Plasma kallikrein

Encoded byKLKB1P03952Homo sapiensSwiss-Prot
UniProt: P03952Ensembl: ENSG00000164344HGNC: HGNC:6371NCBI Gene: 3818
Clinically validated
Therapeutic maturity
6
Approved medicines
Open Targets target-level
View by indication →
14
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Serine-type endopeptidase

Strongest disease association

Venous Thromboembolism

Via encoding gene KLKB1 · Genetic evidence · score 0.82

Therapeutic position

Established drug target

Small molecules and antibodies

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Participates in the surface-dependent activation of blood coagulation.

View complete UniProt function annotation

Participates in the surface-dependent activation of blood coagulation. Activates, in a reciprocal reaction, coagulation factor XII/F12 after binding to negatively charged surfaces. Releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin

Subcellular location

Secreted
Domains and Gene Ontology detail (18)

Domains & features

Apple 1Apple 2Apple 3Apple 4Peptidase S1

Gene Ontology

  • Cextracellular exosome
  • Cextracellular region
  • Cextracellular space
  • Cplasma membrane
  • Fserine-type endopeptidase activity
  • Fserine-type peptidase activity
  • Pblood coagulation
  • PFactor XII activation
  • Pfibrinolysis
  • Pplasminogen activation
  • Ppositive regulation of fibrinolysis
  • Pproteolysis

638 aa · 71 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

HaemostasisUniProt · GOProteolysisGO
View supporting evidence

Haemostasis

  • ·Participates in the surface-dependent activation of blood coagulation. Activates, in a r…
  • ·blood coagulation
  • ·fibrinolysis
  • ·positive regulation of fibrinolysis

Proteolysis

  • ·serine-type endopeptidase activity
  • ·serine-type peptidase activity
  • ·proteolysis

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Angioedemas, Hereditary1 medicine
lanadelumab

6 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

lanadelumab
Narrow target profileApprovedInhibitor

Plasma kallikrein inhibitor

Indicated for Angioedemas, Hereditary

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene KLKB1

Gene-level evidence surfaced through the gene KLKB1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Venous Thromboembolism
0.82Well supported

Genetic evidence dominant · Open Targets 0.50

Angioedemas, Hereditary
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Blood Coagulation Disorders
0.66Moderately supported

Genetic evidence dominant · Open Targets 0.49

Heart Diseases
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.37

Angioedema
0.56Moderately supported

Clinical evidence dominant · Open Targets 0.45

View evidence synthesis (5)
Venous ThromboembolismWell supported
0.82
agreement 0.68–0.96
Genetic100%Literature0%

Open Targets aggregate 0.50 · 2 independent evidence families

Angioedemas, HereditaryModerately supported
0.73
agreement 0.57–0.88
Clinical99%Literature1%

Open Targets aggregate 0.59 · 2 independent evidence families

Blood Coagulation DisordersModerately supported
0.66
agreement 0.52–0.80
Genetic99%Literature2%Genetic literaturedup

Open Targets aggregate 0.49 · 2 independent evidence families · 1 not counted as duplicate

Heart DiseasesModerately supported
0.62
agreement 0.48–0.76
Genetic99%Literature1%

Open Targets aggregate 0.37 · 2 independent evidence families

AngioedemaModerately supported
0.56
agreement 0.40–0.71
Clinical97%Literature3%

Open Targets aggregate 0.45 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Angioedemas, Hereditary0.59
Venous Thromboembolism0.50
Blood Coagulation Disorders0.49
Angioedema0.45
Heart Diseases0.37

Drug development

7 compounds recorded · 6 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
AVORALSTATPhase 2 3
BEROTRALSTATApproval
HUMAN C1-ESTERASE INHIBITORApproval
BEROTRALSTAT HYDROCHLORIDEApproval
APROTININApproval
ECALLANTIDEApproval
LANADELUMABApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Strong

Approved Drug and GO CC high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Approved DrugAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

14

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Lanadelumab in Long-term Prophylaxis of Acquired AngioedemaPHASE4

RECRUITING · via lanadelumab · NCT06818474

A Multi-center, Open-label Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Lanadelumab (SHP643) in Chinese Subjects With Hereditary AngioedemaPHASE3

COMPLETED · via lanadelumab · NCT05460325

An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)PHASE3

COMPLETED · via lanadelumab · NCT04444895

Industry Alliance Platform Trial to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized PatientsPHASE3

COMPLETED · via lanadelumab · NCT04590586

View all trials (10)
A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)PHASE3

COMPLETED · via lanadelumab · NCT04206605

A Phase 3 Multi-center, Open-label Study to Evaluate the Efficacy and Safety of Lanadelumab (SHP643) in Japanese Subjects With Hereditary AngioedemaPHASE3

COMPLETED · via lanadelumab · NCT04180163

SPRING STUDY: An Open-Label, Multicenter, Phase 3 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab for Prevention Against Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects 2 to <12 Years of AgePHASE3

COMPLETED · via lanadelumab · NCT04070326

Prevention of Dialysis-Induced Hypotension by Inhibiting Plasma KallikreinPHASE2

COMPLETED · via lanadelumab · NCT05297786

Lanadelumab for Treatment of COVID-19 DiseasePHASE1/PHASE2

COMPLETED · via lanadelumab · NCT04422509

Factor XII-associated Cold Autoinflammatory Syndrome (FACAS) Linked to Kallikrein-kinin Pathology: Proof of Concept Treatment With Lanadelumab (DX-2930)PHASE2

UNKNOWN · via lanadelumab · NCT04278885

Inhibition of Plasma Kallikrein as a New Therapy for Lung InjuryPHASE1

UNKNOWN · via lanadelumab · NCT04848272

A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 PneumoniaPHASE1

WITHDRAWN · via lanadelumab · NCT04460105

A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer SubjectsPHASE1

COMPLETED · via lanadelumab · NCT04503603

A Phase 1, Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Pharmacodynamics of a Single Dose of Lanadelumab Administered Subcutaneously in Healthy Adult Japanese Subjects and Matched Healthy Adult Caucasian SubjectsPHASE1

COMPLETED · via lanadelumab · NCT03401671

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Label change2026-08-20

    Label change: LANADELUMAB-FLYO (BLA761090)

    fda · regulatory · fda · via lanadelumab

  2. Indication expanded2023-02-03

    Indication expansion: LANADELUMAB-FLYO (BLA761090)

    fda · regulatory · fda · via lanadelumab

  3. Supplemental approval2022-02-08

    Supplemental approval: LANADELUMAB-FLYO (BLA761090)

    fda · regulatory · fda · via lanadelumab

  4. Accelerated approval granted2018-11-22

    Accelerated approval: Takhzyro (EMA)

    ema · regulatory · ema · via lanadelumab

  5. Label change2018-11-16

    Label change: LANADELUMAB-FLYO (BLA761090)

    fda · regulatory · fda · via lanadelumab

  6. Regulatory approval2018-08-23

    Approval: LANADELUMAB-FLYO (BLA761090)

    fda · regulatory · fda · via lanadelumab

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

CRISPR-Cas9 In Vivo Gene Editing of <i>KLKB1</i> for Hereditary Angioedema.126 cites

Longhurst HJ · The New England journal of medicine · 2024

Recent

CRISPR-Cas9 In Vivo Gene Editing of <i>KLKB1</i> for Hereditary Angioedema.

Longhurst HJ · The New England journal of medicine · 2024

Europe PMC papers linked directly to this protein.