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Protein / target

Transmembrane prolyl 4-hydroxylase

Encoded byP4HTMQ9NXG6Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
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

Anemia

Via encoding gene P4HTM · Clinical evidence · score 0.58

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

Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins.

View complete UniProt function annotation

Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex

Subcellular location

Endoplasmic reticulum membrane
Domains and Gene Ontology detail (12)

Domains & features

EF-hand 1EF-hand 2Fe2OG dioxygenase

Gene Ontology

  • Cendoplasmic reticulum
  • Cendoplasmic reticulum membrane
  • F2-oxoglutarate-dependent dioxygenase activity
  • Fcalcium ion binding
  • Fhypoxia-inducible factor-proline dioxygenase activity
  • Firon ion binding
  • FL-ascorbic acid binding
  • Fprocollagen-proline 4-dioxygenase activity
  • Pregulation of erythrocyte differentiation

502 aa · 57 kDa · 3 isoforms

Approved medicines with mapped indications

1 medicine · 2 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.

Anemia1 medicine
Kidney Failure, Chronic1 medicine

2 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.

roxadustat
ApprovedInhibitor

Hypoxia-inducible factor prolyl hydroxylase inhibitor

Indicated for Anemia, Kidney Failure, Chronic

Acts on a complex — shared with EGLN2, 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 P4HTM

Gene-level evidence surfaced through the gene P4HTMthat 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
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Kidney Failure, Chronic
0.61Moderately supported

Clinical evidence dominant · Open Targets 0.49

View evidence synthesis (2)
AnemiaModerately supported
0.72
agreement 0.570.88
Clinical100%Literature1%

Open Targets aggregate 0.58 · 2 independent evidence families

Kidney Failure, ChronicModerately supported
0.61
agreement 0.470.74
Clinical98%RNA expression1%Literature0%

Open Targets aggregate 0.49 · 3 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
Anemia0.58
Kidney Failure, Chronic0.49

Drug development

2 compounds recorded · 2 approved

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 (2)
DAPRODUSTATApproval
ROXADUSTATApproval

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.

AntibodiesEmerging

Feasibility evidence (uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt SigP or TMHMMPR · 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

1

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. 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.