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Protein / target

Neutrophil elastase

Encoded byELANEP08246Homo sapiensSwiss-Prot
UniProt: P08246Ensembl: ENSG00000197561HGNC: HGNC:3309NCBI Gene: 1991
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
Small-molecule tractable
Druggability
Advanced Clinical
1
Research papers

Protein at a glance

Biological role

Serine-type endopeptidase

Strongest disease association

Severe congenital neutropenia

Via encoding gene ELANE · Genetic literature evidence · score 0.87

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

1 papers · latest 2010

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

Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes.

View complete UniProt function annotation

Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes (PubMed:15140022). Shows microbicidal activity in neutrophils by mediating cleavage and degradation of bacterial proteins (PubMed:10947984, PubMed:25161283). Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae (PubMed:10947984). Involved for the formation of neutrophil extracellular traps (NETs): translocates into the nucleus downstream of MPO and mediates degadation of histone H4, thereby participating to chromatin decondensation (PubMed:20974816, PubMed:25066128, PubMed:28574339). NETs are mainly composed of DNA fibers and are released by neutrophils to trap pathogens during inflammation (PubMed:20974816, PubMed:25066128, PubMed:28574339). Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of GSDMB, thereby inhibiting pyroptosis (PubMed:36899106). Promotes blood coagulation (PubMed:20676107). Through the activation of the platelet fibrinogen receptor integrin alpha-IIb/beta-3, potentiates platelet aggregation induced by a threshold concentration of cathepsin G (CTSG) (PubMed:25211214, PubMed:9111081). Cleaves and thus inactivates tissue factor pathway inhibitor (TFPI) (PubMed:20676107, PubMed:25211214)

Subcellular location

Cytoplasmic vesicle, phagosomeLysosomeCytolytic granuleNucleus
Domains and Gene Ontology detail (48)

Domains & features

Peptidase S1

Gene Ontology

  • Cazurophil granule
  • Cazurophil granule lumen
  • Ccell surface
  • Ccytoplasm
  • Ccytosol
  • Cextracellular exosome
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • Cneutrophil extracellular trap
  • Cnucleus
  • Cphagocytic vesicle

267 aa · 29 kDa

Biological roles

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

Cell migrationUniProt · GOProteolysisUniProt · GOImmune signallingGOTranscriptional regulationGOCell adhesionGO
View supporting evidence

Cell migration

  • ·Serine protease that modifies the functions of natural killer cells, monocytes and granu…
  • ·negative regulation of chemotaxis

Proteolysis

  • ·Serine protease that modifies the functions of natural killer cells, monocytes and granu…
  • ·endopeptidase activity
  • ·peptidase activity
  • ·protease binding

Immune signalling

  • ·cytokine binding
  • ·acute inflammatory response to antigenic stimulus
  • ·leukocyte migration involved in inflammatory response
  • ·negative regulation of inflammatory response

Transcriptional regulation

  • ·transcription repressor complex
  • ·transcription corepressor activity
  • ·negative regulation of transcription by RNA polymerase II

Cell adhesion

  • ·extracellular matrix
  • ·extracellular matrix disassembly

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

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 ELANE

Gene-level evidence surfaced through the gene ELANEthat 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.

Neutropenia
0.76Well supported

Genetic evidence dominant · Open Targets 0.59

Severe congenital neutropenia
0.71Moderately supported

Genetic literature evidence dominant · Open Targets 0.54

Pulmonary Emphysema
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.56

View evidence synthesis (3)
NeutropeniaWell supported
0.76
agreement 0.62–0.90
Genetic95%Literature6%Genetic literaturedup

Open Targets aggregate 0.59 · 2 independent evidence families · 1 not counted as duplicate

Severe congenital neutropeniaModerately supported
0.71
agreement 0.56–0.86
Genetic literature92%Literature8%

Open Targets aggregate 0.54 · 2 independent evidence families

Pulmonary EmphysemaModerately supported
0.70
agreement 0.54–0.85
Clinical95%Literature5%

Open Targets aggregate 0.56 · 2 independent evidence families

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
Neutropenia0.59
Pulmonary Emphysema0.56
Severe congenital neutropenia0.54

Drug development

4 compounds recorded · 2 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (4)
SIVELESTATPreapproval
DEPELESTATPhase 2
ALVELESTATPhase 2
.ALPHA.1-PROTEINASE INHIBITOR HUMANApproval

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

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

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 (10)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2010

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

Most cited

Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps.1,611 cites

Papayannopoulos V · The Journal of cell biology · 2010

Recent

Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps.

Papayannopoulos V · The Journal of cell biology · 2010

Europe PMC papers linked directly to this protein.