CYP27B1
Chr 12ARcytochrome P450 family 27 subfamily B member 1
Also known as: CP2B, CYP1, CYP1alpha, CYP27B, P450c1, PDDR, VDD1, VDDR
The protein is a cytochrome P450 monooxygenase that catalyzes the rate-limiting step in vitamin D activation by converting 25-hydroxyvitamin D3 to the hormonally active form 1α,25-dihydroxyvitamin D3, which regulates calcium and phosphorus homeostasis through the vitamin D receptor. Mutations cause vitamin D-dependent rickets type I with autosomal recessive inheritance, affecting bone mineralization and calcium metabolism. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with recessive disease requiring biallelic mutations.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CYP27B1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Vitamin D Dynamics in Women
RECRUITINGVitamin D in Patients With Stage I-III Colon Cancer or Resectable Colon Cancer Liver Metastases
RECRUITINGExternal Resources
Links to major genomics databases and tools