Protein / target

Prolyl hydroxylase EGLN2

Encoded byEGLN2Q96KS0Homo sapiensSwiss-Prot

UniProt: Q96KS0 Ensembl: ENSG00000269858 HGNC: HGNC:14660 NCBI Gene: 112398

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Hypoxia-inducible factor-proline dioxygenase

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene EGLN2 · Genetic evidence · score 0.24

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

Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A.

View complete UniProt function annotation

Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A (PubMed:11595184, PubMed:12039559, PubMed:15925519, PubMed:16509823, PubMed:17114296, PubMed:23932902). Target proteins are preferentially recognized via a LXXLAP motif (PubMed:11595184, PubMed:12039559, PubMed:15925519). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519, PubMed:19339211). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12039559, PubMed:15925519). 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 (PubMed:11595184, PubMed:12039559, PubMed:15925519). EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PubMed:11595184, PubMed:12039559, PubMed:15925519). Also regulates susceptibility to normoxic oxidative neuronal death (PubMed:11595184, PubMed:12039559, PubMed:15925519). Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation (PubMed:23932902). Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (PubMed:17114296). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (By similarity)

Subcellular location

Nucleus

Domains and Gene Ontology detail (18)

Domains & features

Fe2OG dioxygenase

Gene Ontology

Ccytoplasm
Cnucleoplasm
Cnucleus
F2-oxoglutarate-dependent dioxygenase activity
Fferrous iron binding
Fhypoxia-inducible factor-proline dioxygenase activity
FL-ascorbic acid binding
Foxygen sensor activity
Fpeptidyl-proline 4-dioxygenase activity
Pcell redox homeostasis
Pcellular response to hypoxia
Pestrogen receptor signaling pathway

407 aa · 44 kDa · 2 isoforms

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

roxadustat vadadustat

Kidney Failure, Chronic1 medicine

roxadustat

Renal Insufficiency, Chronic1 medicine

vadadustat

4 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

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

Hypoxia-inducible factor prolyl hydroxylase 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 P4HTM, EGLN1, 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 EGLN2

Gene-level evidence surfaced through the gene EGLN2that 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 0.59

Kidney Failure, Chronic

0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Myelodysplastic syndrome

0.28Limited support

Clinical evidence dominant · Open Targets 0.22

Respiratory Distress Syndrome

0.26Limited support

Clinical evidence dominant · Open Targets 0.21

Genetic Diseases, Inborn

0.24Preliminary

Genetic evidence dominant · Open Targets 0.15

View evidence synthesis (5)

AnemiaModerately supported

0.73

agreement 0.58–0.89

Clinical99%Literature1%

Open Targets aggregate 0.59 · 2 independent evidence families

Kidney Failure, ChronicModerately supported

0.69

agreement 0.54–0.85

Clinical99%Literature1%

Open Targets aggregate 0.56 · 2 independent evidence families

Myelodysplastic syndromeLimited support

0.28

agreement 0.12–0.43

Clinical98%Literature2%

Open Targets aggregate 0.22 · 2 independent evidence families

Respiratory Distress SyndromeLimited support

0.26

agreement 0.10–0.41

Clinical96%Literature4%

Open Targets aggregate 0.21 · 2 independent evidence families

Genetic Diseases, InbornPreliminary

0.24

agreement 0.13–0.36

Genetic100%

Open Targets aggregate 0.15 · 1 independent evidence family

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

Anemia0.59

Kidney Failure, Chronic0.56

Neurodegenerative Diseases0.28

Myelodysplastic syndrome0.22

Respiratory Distress Syndrome0.21

Genetic Diseases, Inborn0.15

Drug development

4 compounds recorded · 4 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 (4)

ROXADUSTATApproval

MOLIDUSTATApproval

VADADUSTATApproval

DAPRODUSTATApproval

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.

Protein degraders — Emerging

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

View underlying tractability evidence (7)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

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.

A Prospective Interventional Study Evaluating the Effects of Vadadustat on Anemia, Quality of Life, and Inflammatory Response in Dialysis Patients and Exploring Predictors of Treatment ResponsePHASE4

NOT_YET_RECRUITING · via vadadustat · NCT07537816

Observation of the Impact of Hypoxia - Inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis PatientsPHASE4

NOT_YET_RECRUITING · via roxadustat · NCT07162090

Vadadustat for the Treatment of Nonintubated Acute Respiratory Distress Syndrome Due to Pathogen-Associated Lung InjuryPHASE2/PHASE3

RECRUITING · via vadadustat · NCT07086755

A Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy of Three Times Weekly Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center HemodialysisPHASE3

ACTIVE_NOT_RECRUITING · via vadadustat · NCT06901505

View all trials (26)

Safety of Three Times Weekly Oral Vadadustat for the Treatment of Anemia in Hemodialysis Subjects: Vafseo Outcomes In-Center ExperiencePHASE3

ACTIVE_NOT_RECRUITING · via vadadustat · NCT06520826

Effect of Perioperative Roxadustat in Elective Lumbar Interbody Fusion Surgery: a Parallel-group, Open-label, Randomised Controlled Trial.PHASE3

ACTIVE_NOT_RECRUITING · via roxadustat · NCT06772272

A Phase 3, Open-label, Uncontrolled Study to Evaluate the Activity, Safety, Pharmacokinetics and Pharmacodynamics of Roxadustat for the Treatment of Anemia in Pediatric Participants With Chronic Kidney DiseasePHASE3

RECRUITING · via roxadustat · NCT05970172

The Effect of Roxadustat on the Levels of Renal Oxygenation in Patients With Diabetes Nephropathy (FOXTROT)PHASE2

NOT_YET_RECRUITING · via roxadustat · NCT05810311

Effect of Roxadustat on Cardiovascular System and Malnutrition-Inflammation-Atherosclerosis (MIA) Syndrome in Hemodialysis Patients: A Randomized Controlled StudyPHASE1/PHASE2

RECRUITING · via roxadustat · NCT06903559

Effect of Roxadustat on Bone and Neuropsychiatric Aspects in End Stage Kidney Disease Patients on HemodialysisPHASE1/PHASE2

RECRUITING · via roxadustat · NCT06917950

Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory Myelodysplastic Syndrome With Ring Sideroblasts (MDS-RS): A Prospective Randomized Controlled StudyPHASE4

UNKNOWN · via roxadustat · NCT06006949

Effect of Low Doses of Hypoxia-inducible Factor- Prolyl Hydroxylase Enzyme Inhibitor Plus Iron in the Treatment of Anemia in Dialysis-dependent Chronic Kidney Disease PatientsPHASE4

COMPLETED · via roxadustat · NCT06115421

Study of the Safety and Efficacy of Roxadustat in the Treatment of Heart Failure With Chronic Kidney Disease and AnemiaPHASE4

UNKNOWN · via roxadustat · NCT05691257

Clinical Observation of Roxadustat's Effect on Anemia in Patients With Diabetic Kidney Disease (Stage III-IV)PHASE4

COMPLETED · via roxadustat · NCT07359027

ALTAI: An Open-Label, Randomized, Active-Controlled, Parallel Design, Multicenter Phase IV Study to Investigate the Effect of Roxadustat Versus Recombinant Human Erythropoietin (rHuEPO) on Oral Iron Absorption in Chinese Patients With Anemia of Chronic Kidney Disease (CKD)PHASE4

COMPLETED · via roxadustat · NCT04655027

Different Doses of Roxadustat Treatment on Hemoglobin Target-met in Peritoneal Dialysis PatientsPHASE4

COMPLETED · via roxadustat · NCT04454879

A Prospective, Randomized, Open-Label, Multi-Center Study to Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Subjects With Chronic Kidney DiseasePHASE4

COMPLETED · via roxadustat · NCT04059913

A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of Once Daily Oral Vadadustat for the Treatment of Pediatric Subjects With Anemia of Chronic Kidney Disease After Conversion From an Erythropoiesis-stimulating AgentPHASE3

WITHDRAWN · via vadadustat · NCT05082571

A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of Once Daily Oral Vadadustat for The Treatment of Pediatric Subjects With Anemia of Chronic Kidney Disease Naive to Erythropoiesis-stimulating AgentsPHASE3

WITHDRAWN · via vadadustat · NCT05082584

An Open-label, Multicenter Study Investigating the Efficacy, Safety and Pharmacokinetics of Roxadustat (FG-4592) for Treatment of Anemia in Pediatric Patients With Chronic Kidney DiseasePHASE3

WITHDRAWN · via roxadustat · NCT04621331

A Randomized, Open-label, Active-controlled, Multicenter Phase 3 Study to Investigate the Efficacy and Safety of Roxadustat for Treatment of Anemia in Subjects Receiving Chemotherapy Treatment for Non-Myeloid MalignanciesPHASE3

COMPLETED · via roxadustat · NCT05301517

An Open-label, One-center Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Pediatric Patients With Chronic Kidney DiseasePHASE3

UNKNOWN · via roxadustat · NCT04925011

A Randomized, Open-label, Active-controlled Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis SubjectsPHASE3

COMPLETED · via vadadustat · NCT04707768

Phase 3b Multicenter, Open-Label Single Arm Study of Roxadustat: Either as Conversion From an Erythropoiesis Stimulating Agent (ESA), or as Initial Anemia Treatment in Hemodialysis (HD) PatientsPHASE3

COMPLETED · via roxadustat · NCT04484857

Phase 3b, Randomized, Open-label, Active-controlled Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs)PHASE3

COMPLETED · via vadadustat · NCT04313153

A Phase 3b Multicenter, Open-Label Single Arm Study of Roxadustat: Either as Conversion From a Continuous Erythropoietin Receptor Activator (CERA), or as Initial Anemia Treatment in Hemodialysis (HD) Patients - DENALI StudyPHASE3

COMPLETED · via roxadustat · NCT04410198

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients With Lower Risk Myelodysplastic Syndrome (MDS) With Low Red Blood Cell (RBC) Transfusion Burden (LTB)PHASE3

TERMINATED · via roxadustat · NCT03263091

Phase 3, Randomized, Open Label, Active Controlled Study Evaluating the Efficacy and Safety of Three Times Per Week (TIW) Oral Dosing of Vadadustat for the Treatment of Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (TRILO2GY)PHASE3

WITHDRAWN · via vadadustat · NCT03242967

A Phase 3 Multi-center, Randomized, Open-label, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Non-dialysis Chronic Kidney Disease Patients With AnemiaPHASE3

COMPLETED · via roxadustat · NCT02988973

A Phase 3, Multicenter, Randomized, 2-Arm, Open-label Study of Intermittent Oral Dosing of ASP1517 for the Treatment of Anemia in Erythropoiesis Stimulating Agent-untreated Chronic Kidney Disease Patients Not on DialysisPHASE3

COMPLETED · via roxadustat · NCT02964936

ClinicalTrials.gov via the drug-target graph.

What's happening now

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.

Regulatory approval2023-04-24
Approval: Vafseo (EMA)
ema · regulatory · ema · via vadadustat
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.