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CYP27B1

cytochrome P450 family 27 subfamily B member 1

The CYP27B1 gene provides instructions for an enzyme crucial in converting vitamin D into its active form, calcitriol, which is vital for maintaining calcium and phosphate balance. CYP27B1 encodes a cytochrome P450 enzyme responsible for the final step in activating vitamin D.

Chromosome 12q14.1 Autosomal recessive HGNC:2606 Tier C
CYP27B1 12q14.1 p arm q arm 12

CYP27B1 is located on the long (q) arm of chromosome 12, at band 12q14.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 12 in the library →

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Clinical tests that include this

Carrier Screening panel
CYP27B1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
CYP27B1 is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The CYP27B1 gene is responsible for producing an enzyme that belongs to the cytochrome P450 family. These enzymes are known for their involvement in various metabolic processes, including the breakdown of medicines and hormones, as well as the production of cholesterol and fats. The CYP27B1 enzyme specifically plays a key role in vitamin D metabolism, converting it into its biologically active form.

What the gene does

The CYP27B1 enzyme, a member of the cytochrome P450 family, is primarily located within the mitochondria of cells, which are the energy-producing organelles. This enzyme performs the second of two essential reactions required to transform vitamin D into calcitriol, its active form. Calcitriol is crucial for the proper regulation of calcium and phosphate levels in the blood. These minerals are vital for the development and strength of bones and teeth. A major function of active vitamin D is to facilitate the absorption of calcium and phosphate from the intestines into the bloodstream, thereby supporting skeletal health.

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Chromosome location

The CYP27B1 gene is situated on chromosome 12 at position 12q14.1. This location specifies the long (q) arm of chromosome 12, within region 1, band 4, sub-band 1.

Protein structure

The CYP27B1 protein consists of 508 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants within the CYP27B1 gene can lead to altered enzyme function, impacting the body's ability to activate vitamin D. These genetic changes may disrupt the critical step of converting inactive vitamin D into calcitriol, leading to impaired mineral balance and bone health.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for CYP27B1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1165C>T
single nucleotide variant
 p.Arg389Cys Pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.1294C>T
single nucleotide variant
 p.Arg432Cys Pathogenic/Likely pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.1376G>A
single nucleotide variant
 p.Arg459His Pathogenic/Likely pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.1376G>T
single nucleotide variant
 p.Arg459Leu Pathogenic/Likely pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.160_161dup
Duplication
 p.Lys55fs Pathogenic/Likely pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.170G>T
single nucleotide variant
 p.Gly57Val Pathogenic/Likely pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.171del
Deletion
 p.Leu58fs Pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.196-2A>G
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ CYP27B1-related disorder
c.335C>T
single nucleotide variant
 p.Pro112Leu Pathogenic/Likely pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A
c.57_69del
Deletion
 p.Glu20fs Pathogenic ★★☆☆ Vitamin D-dependent rickets, type 1A

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the CYP27B1 gene are known to cause Vitamin D-dependent rickets type 1. This condition is characterised by soft, weak bones prone to fractures and deformities, such as abnormally curved limbs.

  • Vitamin D-dependent rickets type 1
    Skeletal
    AR
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Inheritance pattern

Conditions caused by pathogenic CYP27B1 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous CYP27B1 carrier status across ancestry groups?

UK clinical status

CYP27B1 is recognised in the UK by NHS England's Genomic Medicine Service, being listed on PanelApp for its association with Hypophosphataemia or rickets (green status on panel R154) and Skeletal dysplasia (green status on panel R104).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Hypophosphataemia or rickets · R154 NHS GMS → Skeletal dysplasia · R104 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main role of the CYP27B1 gene?

The CYP27B1 gene provides instructions for an enzyme that converts vitamin D into its active form, calcitriol. Calcitriol is essential for maintaining proper calcium and phosphate levels in the blood, which are crucial for strong bones and teeth.

What condition is associated with variants in the CYP27B1 gene?

Pathogenic variants in the CYP27B1 gene are associated with Vitamin D-dependent rickets type 1. This inherited condition primarily affects bone development, leading to weak and soft bones that are susceptible to fractures and deformities.

How does activated vitamin D affect the body?

Activated vitamin D, known as calcitriol, plays a key role in regulating how the body absorbs calcium and phosphate from the intestines. This process is vital for bone mineralisation and overall skeletal health.

References

  1. Demir K, Kattan WE, Zou M. Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A. PloS one. 2015. PMID: 26132292
  2. Nebert DW, Wikvall K, Miller WL. Human cytochromes P450 in health and disease. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2013. PMID: 23297354
  3. Ryan JW, Anderson PH, Turner AG. Vitamin D activities and metabolic bone disease. Clinica chimica acta; international journal of clinical chemistry. 2013. PMID: 23911750
  4. Durmaz E, Zou M, Al-Rijjal RA. Clinical and genetic analysis of patients with vitamin D-dependent rickets type 1A. Clinical endocrinology. 2012. PMID: 22443290
  5. Malloy PJ, Feldman D. Genetic disorders and defects in vitamin D action. Rheumatic diseases clinics of North America. 2012. PMID: 22525845
  6. Kim CJ, Kaplan LE, Perwad F. Vitamin D 1alpha-hydroxylase gene mutations in patients with 1alpha-hydroxylase deficiency. The Journal of clinical endocrinology and metabolism. 2007. PMID: 17488797
  7. Portale AA, Miller WL. Human 25-hydroxyvitamin D-1alpha-hydroxylase: cloning, mutations, and gene expression. Pediatric nephrology (Berlin, Germany). 2000. PMID: 10912530
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .