Protein / target
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
Protein at a glance
Biological role
Secalciferol 1-monooxygenase
Strongest disease association
Genetic Diseases, Inborn
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis.
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A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis. Catalyzes the rate-limiting step in the activation of vitamin D in the kidney, namely the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1alpha-position to form the hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3/calcitriol that acts via the vitamin D receptor (VDR) (PubMed:10518789, PubMed:10566658, PubMed:12050193, PubMed:22862690, PubMed:9486994). Has 1alpha-hydroxylase activity on vitamin D intermediates of the CYP24A1-mediated inactivation pathway (PubMed:10518789, PubMed:22862690). Converts 24R,25-dihydroxyvitamin D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR. Also active on 25-hydroxyvitamin D2 (PubMed:10518789). 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:22862690)
Subcellular location
Domains and Gene Ontology detail (26)Hide
Gene Ontology
- Ccytoplasm
- Cmitochondrial outer membrane
- Cmitochondrion
- Fcalcidiol 1-monooxygenase activity
- Fheme binding
- Firon ion binding
- Fsecalciferol 1-monooxygenase activity
- Pbone mineralization
- Pcalcitriol biosynthetic process from calciol
- Pcalcium ion homeostasis
- Pcalcium ion transport
- Pcellular response to vitamin D
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Cell proliferation & survival
- ·negative regulation of cell population proliferation
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
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 CYP27B1
Gene-level evidence surfaced through the gene CYP27B1 that 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.
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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.
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Tractability
Small molecules — Emerging
Protein degraders — Emerging
View underlying tractability evidence (3)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
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
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.