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Protein / target

Vitamin D3 receptor

Encoded byVDRP11473Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
9
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Bile acid nuclear receptor

Strongest disease association

Hypocalcemic vitamin D-resistant rickets

Via encoding gene VDR · Genetic evidence · score 0.92

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

Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.

View complete UniProt function annotation

Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:10678179, PubMed:15728261, PubMed:16913708, PubMed:28698609, PubMed:37478846). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638)

Subcellular location

NucleusCytoplasm
Domains and Gene Ontology detail (38)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytoplasm
  • Cnucleoplasm
  • Cnucleus
  • Creceptor complex
  • CRNA polymerase II transcription regulator complex
  • Fbile acid nuclear receptor activity
  • Fcalcitriol binding
  • FDNA binding
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Flithocholic acid binding
  • Fnuclear receptor activity

427 aa · 48 kDa · 2 isoforms

Biological roles

Reactome v97

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

Nuclear receptor signallingUniProt · GO · ReactomeIon channel gatingGOCell proliferation & survivalGOTranscriptional regulationUniProt · GO · Reactome
View supporting evidence

Nuclear receptor signalling

  • ·Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action…
  • ·bile acid nuclear receptor activity
  • ·nuclear receptor activity
  • ·nuclear receptor-mediated bile acid signaling pathway

Ion channel gating

  • ·phosphate ion transmembrane transport

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Transcriptional regulation

  • ·Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action…
  • ·RNA polymerase II transcription regulator complex
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·RNA polymerase II cis-regulatory region sequence-specific DNA binding
View underlying pathways (3)

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

Approved medicines with mapped indications

4 medicines · 9 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.

Hypoparathyroidism2 medicines
Anemia1 medicine
Anemia, Iron-Deficiency1 medicine
Hyperparathyroidism, Secondary1 medicine
Kidney Failure, Chronic1 medicine
Osteoporosis1 medicine
Parathyroid Diseases1 medicine
Psoriasis1 medicine
Renal Insufficiency, Chronic1 medicine

9 medicines meet Open Targets' target-level approved-medicine definition; the 4 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

4

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.

Calcitriol
Narrow target profileApprovedAgonist

Vitamin D receptor agonist

Indicated for Hypoparathyroidism, Kidney Failure, Chronic, Psoriasis

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

paricalcitol
Narrow target profileApprovedAgonist

Vitamin D receptor agonist

Indicated for Hyperparathyroidism, Secondary, Parathyroid Diseases, Renal Insufficiency, Chronic

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

Vitamin D
Narrow target profileAgonist

Vitamin D receptor agonist

Indicated for Hypoparathyroidism

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

Cholecalciferol
Narrow target profileApprovedAgonist

Vitamin D receptor agonist

Indicated for Anemia, Anemia, Iron-Deficiency, Osteoporosis

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 VDR

Gene-level evidence surfaced through the gene VDRthat 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.

Hypocalcemic vitamin D-resistant rickets
0.95Well supported

Genetic evidence dominant · Open Targets 0.82

Osteoporosis
0.80Well supported

Clinical evidence dominant · Open Targets 0.61

Psoriasis
0.78Well supported

Clinical evidence dominant · Open Targets 0.63

Kidney Failure, Chronic
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Vitamin D Deficiency
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

View evidence synthesis (5)
Hypocalcemic vitamin D-resistant ricketsWell supported
0.95
agreement 0.821.00
Genetic77%Animal model23%Genetic literaturedup

Open Targets aggregate 0.82 · 2 independent evidence families · 1 not counted as duplicate

OsteoporosisWell supported
0.80
agreement 0.680.93
Clinical68%Animal model19%Literature13%

Open Targets aggregate 0.61 · 3 independent evidence families

PsoriasisWell supported
0.78
agreement 0.620.93
Clinical85%Literature15%

Open Targets aggregate 0.63 · 2 independent evidence families

Kidney Failure, ChronicWell supported
0.77
agreement 0.610.92
Clinical88%Literature12%

Open Targets aggregate 0.62 · 2 independent evidence families

Vitamin D DeficiencyModerately supported
0.75
agreement 0.590.90
Clinical92%Literature8%

Open Targets aggregate 0.61 · 2 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
Hypocalcemic vitamin D-resistant rickets0.82
Psoriasis0.63
Kidney Failure, Chronic0.62
Osteoporosis0.61
Vitamin D Deficiency0.61
Secondary hyperparathyroidism0.60
Psoriasis vulgaris0.60
Hypoparathyroidism0.58
Anemia0.52

Drug development

18 compounds recorded · 9 approved · 9 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
SEOCALCITOLPhase 3
PARICALCITOLApproval
BECOCALCIDIOLPhase 2
ELDECALCITOLApproval
ERGOCALCIFEROLApproval
CALCIPOTRIENEApproval
INECALCITOLPhase 2
CALCITRIOLApproval
CALCIFEDIOLApproval
DIHYDROTACHYSTEROLApproval

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 · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

anemiaClinPGxregulation of transcription factor activityToxCast

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)

TERMINATED · via Cholecalciferol · NCT02208310

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 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. Label change2026-06-17

    Label change: PARICALCITOL (NDA205917)

    fda · regulatory · fda · via paricalcitol

  2. New publication2025-09-09
    Randomized trial of activated vitamin D for acute kidney injury prevention in critically ill patients.

    JCI insight · 2025 · 1 citation · Europe PMC · via Calcitriol

  3. New publication2025-05-16
    Molecular Insight into the Role of Vitamin D in Immune-Mediated Inflammatory Diseases.

    International journal of molecular sciences · 2025 · 8 citations · Europe PMC · via Vitamin D

  4. New publication2025-01-01
    Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.

    The oncologist · 2025 · 7 citations · Europe PMC · via paricalcitol

  5. New publication2024-11-01
    High-dose vitamin D supplementation does not improve outcome in a cutaneous melanoma population: results of a randomized double-blind placebo-controlled study (ViDMe trial).

    The British journal of dermatology · 2024 · 4 citations · Europe PMC · via Vitamin D

  6. New publication2024-09-20
    Multifaceted Roles of Vitamin D for Diabetes: From Immunomodulatory Functions to Metabolic Regulations.

    Nutrients · 2024 · 19 citations · Europe PMC · via Vitamin D

  7. New publication2024-04-30
    Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights.

    International journal of molecular sciences · 2024 · 30 citations · Europe PMC · via Vitamin D

  8. New publication2024-04-28
    Role of Calcitriol and Vitamin D Receptor (<i>VDR</i>) Gene Polymorphisms in Alzheimer's Disease.

    International journal of molecular sciences · 2024 · 17 citations · Europe PMC · via Calcitriol

  9. New publication2024-04-19
    Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology.

    Frontiers in endocrinology · 2024 · 12 citations · Europe PMC · via Vitamin D

  10. New publication2023-12-21
    Effects of vitamin D supplementation on metabolic parameters, serum irisin and obesity values in women with subclinical hypothyroidism: a double-blind randomized controlled trial.

    Frontiers in endocrinology · 2023 · 10 citations · Europe PMC · via Vitamin D

  11. New publication2023-12-03
    Vitamin D<sub>3</sub> Receptors and Metabolic Enzymes in Hen Reproductive Tissues.

    International journal of molecular sciences · 2023 · 11 citations · Europe PMC · via Cholecalciferol

  12. Regulatory approval2014-11-18

    Approval: PARICALCITOL (NDA205917)

    fda · regulatory · fda · via paricalcitol

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.