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Protein / target

Endothelial PAS domain-containing protein 1

Encoded byEPAS1Q99814Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein heterodimerization

Strongest disease association

Erythrocytosis, familial, 4

Via encoding gene EPAS1 · Genetic evidence · score 0.90

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

Transcription factor involved in the induction of oxygen regulated genes.

View complete UniProt function annotation

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 · Reactome
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
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.

Approved medicines with mapped indications

1 medicine · 5 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.

Carcinoma, Renal Cell1 medicine
Hemangioblastoma1 medicine
Neuroendocrine Tumors1 medicine
von Hippel-Lindau Disease1 medicine
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

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.

belzutifan
Narrow target profileApprovedInhibitor

Endothelial PAS domain-containing protein 1 inhibitor

Indicated for Carcinoma, Renal Cell, Hemangioblastoma, Neuroendocrine Tumors, von Hippel-Lindau Disease

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

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 EPAS1

Gene-level evidence surfaced through the gene EPAS1that 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.

Carcinoma, Renal Cell
0.93Well supported

Genetic evidence dominant · Open Targets 0.65

Erythrocytosis, familial, 4
0.92Well supported

Genetic evidence dominant · Open Targets 0.75

Atrial Fibrillation
0.73Moderately supported

Genetic evidence dominant · Open Targets 0.44

Autosomal dominant secondary polycythemia
0.71Moderately supported

Genetic evidence dominant · Open Targets 0.52

Neoplasms
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.46

View evidence synthesis (5)
Carcinoma, Renal CellWell supported
0.93
agreement 0.841.00
Genetic38%Clinical37%Somatic mutation17%Literature8%

Open Targets aggregate 0.65 · 4 independent evidence families

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

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

NeoplasmsModerately supported
0.68
agreement 0.560.80
Clinical51%Somatic mutation33%Literature16%

Open Targets aggregate 0.46 · 3 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Erythrocytosis, familial, 40.75
Carcinoma, Renal Cell0.65
Autosomal dominant secondary polycythemia0.52
von Hippel-Lindau Disease0.51
Paraganglioma0.48
Neoplasms0.46
Hemangioblastoma0.44
Atrial Fibrillation0.44
Pancreatic neuroendocrine tumor0.44

Drug development

1 compounds recorded · 1 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 (1)
BELZUTIFANApproval

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

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

drug toxicityClinPGxdermatologic toxicityClinPGx

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.

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)

ACTIVE_NOT_RECRUITING · via belzutifan · NCT04489771

ClinicalTrials.gov via the drug-target graph.

What's happening now

9

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. Indication expanded2026-06-12

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  2. Indication expanded2025-05-14

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  3. Indication expanded2025-04-15

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  4. Indication expanded2025-04-15

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  5. Regulatory approval2025-02-12

    Approval: Welireg (EMA)

    ema · regulatory · ema · via belzutifan

  6. Label change2024-02-26

    Label change: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  7. Indication expanded2023-12-14

    Indication expansion: BELZUTIFAN (NDA215383)

    fda · regulatory · fda · via belzutifan

  8. 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

  9. 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.