Protein / target

Endothelial PAS domain-containing protein 1

EPAS1Q99814Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein heterodimerization activity

Primary system

Cardiovascular system

Strongest disease association

erythrocytosis, familial, 4

Genetic evidence · score 0.90

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

1 approved

30 linked trials

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

Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX1 seems to activate CTAD (By similarity)

Subcellular location

NucleusNucleus speckle
Domains and Gene Ontology detail (31)

Domains & features

bHLHPAS 1PAS 2PAC

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cnuclear speck
  • Cnucleoplasm
  • Cnucleus
  • Ctranscription regulator complex
  • FDNA-binding transcription activator activity, RNA polymerase II-specific
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fprotein heterodimerization activity
  • FRNA polymerase II cis-regulatory region sequence-specific DNA binding
  • FRNA polymerase II transcription regulatory region sequence-specific DNA binding
  • FRNA polymerase II-specific DNA-binding transcription factor binding

870 aa · 96 kDa

Biological roles

Reactome v97

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

Transcriptional regulationUniProt · GO · ReactomeNuclear receptor signallingGO
View supporting evidence

Transcriptional regulation

  • ·Transcription factor involved in the induction of oxygen regulated genes. Heterodimerize…
  • ·transcription regulator complex
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
View underlying pathways (8)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

EGLN1VHLARNTEGLN3EP300HIF1AEGLN2ARNT2HIF3AELOBEPAS1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

belzutifan
Narrow target profileApprovedInhibitor

Endothelial PAS domain-containing protein 1 inhibitor

Appears in clinical studies involving von Hippel-Lindau disease, renal cell carcinoma, neoplasm, hemangioblastoma

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

erythrocytosis, familial, 40.90

Genetic · overall 0.75

atrial fibrillation0.72

Genetic · overall 0.44

autosomal dominant secondary polycythemia0.68

Genetic literature · overall 0.52

renal cell carcinoma0.68

Genetic · overall 0.65

clear cell renal carcinoma0.66

Genetic · overall 0.53

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

von Hippel-Lindau disease0.84

Clinical · overall 0.51

neoplasm0.62

Clinical · overall 0.46

hemangioblastoma0.61

Clinical · overall 0.44

pancreatic neuroendocrine tumor0.61

Clinical · overall 0.44

paraganglioma0.12

Clinical · overall 0.48

Show all associations
erythrocytosis, familial, 40.75
renal cell carcinoma0.65
clear cell renal carcinoma0.53
autosomal dominant secondary polycythemia0.52
von Hippel-Lindau disease0.51
paraganglioma0.48
neoplasm0.46
hemangioblastoma0.44
atrial fibrillation0.44
pancreatic neuroendocrine tumor0.44

Open Targets ranks 1,273 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 1 total

BELZUTIFANApproval

von Hippel-Lindau disease · renal cell carcinoma · neoplasm

Tractability

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

Safety liabilities

drug toxicitydermatologic toxicity

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.

Show remaining trials (24)

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

erythrocytosis, familial, 4Well supported
0.92
agreement 0.801.00
Genetic81%Animal model18%Literature1%Genetic literaturedup

Open Targets aggregate 0.75 · 3 independent evidence families · 1 not counted as duplicate

renal cell carcinomaWell supported
0.91
agreement 0.801.00
Genetic46%Clinical44%Literature10%

Open Targets aggregate 0.65 · 3 independent evidence families

clear cell renal carcinomaWell supported
0.88
agreement 0.780.97
Genetic46%Clinical31%Somatic mutation20%Literature3%

Open Targets aggregate 0.53 · 4 independent evidence families

atrial fibrillationModerately supported
0.73
agreement 0.590.87
Genetic97%Literature3%

Open Targets aggregate 0.44 · 2 independent evidence families

autosomal dominant secondary polycythemiaModerately supported
0.71
agreement 0.580.83
Genetic71%Animal model29%Genetic literaturedup

Open Targets aggregate 0.52 · 2 independent evidence families · 1 not counted as duplicate

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

10

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. Regulatory action2026-06-15
    Merck's Welireg-Keytruda pairing sticks the landing in adjuvant kidney cancer treatment with new FDA nod

    Fierce Pharma · news · via belzutifan

  2. Indication expanded2026-06-12

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  3. Indication expanded2025-05-14

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  4. Indication expanded2025-04-15

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  5. Indication expanded2025-04-15

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  6. Regulatory approval2025-02-12

    Approval: Welireg (EMA)

    ema · regulatory · ema · via belzutifan

  7. Label change2024-02-26

    Label change: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  8. Indication expanded2023-12-14

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  9. New publication2021-11-01
    Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease.

    The New England journal of medicine · 2021 · 532 citations · Europe PMC · via belzutifan

  10. Regulatory approval2021-08-13

    Approval: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

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.