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Protein / target

1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

Encoded byCYP24A1Q07973Homo sapiensSwiss-Prot
UniProt: Q07973Ensembl: ENSG00000019186HGNC: HGNC:2602NCBI Gene: 1591
Small-molecule tractable
Druggability
High-Quality Ligand
1
Research papers

Protein at a glance

Biological role

1-alpha,25-dihydroxyvitamin D3 23-hydroxylase

Strongest disease association

Nephrolithiasis

Via encoding gene CYP24A1 · Genetic evidence · score 0.90

Research activity

Emerging research

1 papers · latest 2023

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

A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis.

View complete UniProt function annotation

A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:11012668, PubMed:15574355, PubMed:16617161, PubMed:24893882, PubMed:29461981, PubMed:8679605). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:15574355, PubMed:24893882). With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product (PubMed:11012668, PubMed:8679605). Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:8679605)

Subcellular location

Mitochondrion
Domains and Gene Ontology detail (15)

Gene Ontology

  • Cmitochondrial inner membrane
  • Cmitochondrion
  • F1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity
  • F1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity
  • F25-hydroxycholecalciferol-23-hydroxylase activity
  • F25-hydroxycholecalciferol-24-hydroxylase activity
  • Fheme binding
  • Firon ion binding
  • Fvitamin D3 25-hydroxylase activity
  • Posteoblast differentiation
  • Presponse to vitamin D
  • Pvitamin D catabolic process

514 aa · 59 kDa · 3 isoforms

Biological roles

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

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·vitamin D metabolic process
  • ·vitamin metabolic process

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

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 CYP24A1

Gene-level evidence surfaced through the gene CYP24A1that 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.

Nephrolithiasis
0.90Well supported

Genetic evidence dominant · Open Targets 0.55

Dermatitis, Atopic
0.86Well supported

Genetic evidence dominant · Open Targets 0.53

Ureterolithiasis
0.82Well supported

Genetic evidence dominant · Open Targets 0.50

Bladder calculus
0.78Well supported

Genetic evidence dominant · Open Targets 0.47

Genetic Diseases, Inborn
0.78Well supported

Genetic evidence dominant · Open Targets 0.47

View evidence synthesis (5)
NephrolithiasisWell supported
0.90
agreement 0.76–1.00
Genetic96%Literature4%

Open Targets aggregate 0.55 · 2 independent evidence families

Dermatitis, AtopicWell supported
0.86
agreement 0.72–1.00
Genetic98%Literature3%

Open Targets aggregate 0.53 · 2 independent evidence families

UreterolithiasisWell supported
0.82
agreement 0.70–0.94
Genetic100%

Open Targets aggregate 0.50 · 1 independent evidence family

Bladder calculusWell supported
0.78
agreement 0.66–0.90
Genetic100%

Open Targets aggregate 0.47 · 1 independent evidence family

Genetic Diseases, InbornWell supported
0.78
agreement 0.64–0.92
Genetic99%Literature1%

Open Targets aggregate 0.47 · 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
Nephrolithiasis0.55
Dermatitis, Atopic0.53
Ureterolithiasis0.50
Neurodegenerative Diseases0.48
Bladder calculus0.47
Genetic Diseases, Inborn0.47
Multiple Sclerosis0.46
Urolithiasis0.45

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand and druggable family) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

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

View underlying tractability evidence (4)
SM · High-Quality LigandSM · Druggable FamilyPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

nephrotoxicityClinPGxregulation 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.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Vitamin D<sub>3</sub> Receptors and Metabolic Enzymes in Hen Reproductive Tissues.11 cites

Hrabia A · International journal of molecular sciences · 2023

Recent

Vitamin D<sub>3</sub> Receptors and Metabolic Enzymes in Hen Reproductive Tissues.

Hrabia A · International journal of molecular sciences · 2023

Europe PMC papers linked directly to this protein.