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Protein / target

Egl nine homolog 1

Encoded byEGLN1Q9GZT9Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Hypoxia-inducible factor-proline dioxygenase

Strongest disease association

Autosomal dominant secondary polycythemia

Via encoding gene EGLN1 · Genetic evidence · score 0.61

Therapeutic position

Established drug target

Small molecules

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

Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins.

View complete UniProt function annotation

Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif

Subcellular location

CytoplasmNucleus
Domains and Gene Ontology detail (26)

Domains & features

Fe2OG dioxygenase

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cglutamatergic synapse
  • Cnucleus
  • Cpostsynaptic density
  • F2-oxoglutarate-dependent dioxygenase activity
  • Fenzyme binding
  • Fenzyme inhibitor activity
  • Fferrous iron binding
  • Fhypoxia-inducible factor-proline dioxygenase activity
  • FL-ascorbic acid binding
  • Fpeptidyl-proline 4-dioxygenase activity

426 aa · 46 kDa · 3 isoforms

Biological roles

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

Synaptic signallingGO
View supporting evidence

Synaptic signalling

  • ·glutamatergic synapse
  • ·postsynaptic density
  • ·regulation of modification of postsynaptic structure
  • ·regulation protein catabolic process at postsynapse

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

Approved medicines with mapped indications

2 medicines · 3 areas

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.

Anemia2 medicines
Kidney Failure, Chronic1 medicine
Renal Insufficiency, Chronic1 medicine

5 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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.

vadadustat
Narrow target profileApprovedInhibitor

Egl nine homolog 1 inhibitor

Indicated for Anemia, Renal Insufficiency, Chronic

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

roxadustat
ApprovedInhibitor

Hypoxia-inducible factor prolyl hydroxylase inhibitor

Indicated for Anemia, Kidney Failure, Chronic

Acts on a complex — shared with EGLN2, P4HTM, EGLN3 · 1 of 4 recorded protein targets

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 EGLN1

Gene-level evidence surfaced through the gene EGLN1that 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.

Anemia
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.60

Autosomal dominant secondary polycythemia
0.71Moderately supported

Genetic evidence dominant · Open Targets 0.47

Kidney Failure, Chronic
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Kidney Diseases
0.32Limited support

Clinical evidence dominant · Open Targets 0.26

Neurodegenerative Diseases
0.32Preliminary

Pathway evidence dominant · Open Targets 0.48 · no direct causal or clinical evidence

View evidence synthesis (5)
AnemiaModerately supported
0.73
agreement 0.580.89
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

Autosomal dominant secondary polycythemiaModerately supported
0.71
agreement 0.590.83
Genetic70%Animal model30%Literature1%Genetic literaturedup

Open Targets aggregate 0.47 · 3 independent evidence families · 1 not counted as duplicate

Kidney Failure, ChronicModerately supported
0.69
agreement 0.540.85
Clinical98%Literature2%

Open Targets aggregate 0.56 · 2 independent evidence families

Kidney DiseasesLimited support
0.32
agreement 0.170.48
Clinical99%Literature1%

Open Targets aggregate 0.26 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary
0.32
agreement 0.140.49
Pathway99%Literature1%

Open Targets aggregate 0.48 · 2 independent evidence families · no direct causal or clinical evidence

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
Anemia0.60
Kidney Failure, Chronic0.56
Neurodegenerative Diseases0.48
Autosomal dominant secondary polycythemia0.47
Kidney Diseases0.26

Drug development

5 compounds recorded · 5 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (5)
DAPRODUSTATApproval
VADADUSTATApproval
ROXADUSTATApproval
ENARODUSTATApproval
MOLIDUSTATApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

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.

View all trials (26)

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target 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. Regulatory approval2023-04-24

    Approval: Vafseo (EMA)

    ema · regulatory · ema · via vadadustat

  2. Regulatory approval2021-08-18

    Approval: Evrenzo (EMA)

    ema · regulatory · ema · via roxadustat

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.