CYP2R1
Cytochrome P450 Family 2 Subfamily R Member 1
Gene Information Card
| Symbol | CYP2R1 |
|---|---|
| Full Name | Cytochrome P450 Family 2 Subfamily R Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.2 |
| NCBI Gene ID | 120227 ncbi.nlm.nih.gov/gene/120227 |
| Ensembl ID | ENSG00000186104 |
| UniProt ID | Q6VVX0 |
| OMIM ID | 608713 |
| HGNC ID | 20580 |
| Aliases | Vitamin D 25-hydroxylase, CYP2R, D25H |
Description
CYP2R1 encodes a member of the cytochrome P450 superfamily of enzymes. This microsomal protein is the primary vitamin D 25-hydroxylase, catalyzing the first hydroxylation step in vitamin D activation, converting vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) to 25-hydroxyvitamin D (calcifediol). This enzyme is essential for maintaining adequate vitamin D status and calcium homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Vitamin D-dependent rickets type 1B (VDDR1B) | Loss-of-function mutations in CYP2R1 impair 25-hydroxylation of vitamin D, leading to low 25-hydroxyvitamin D levels and defective bone mineralization. | OMIM #600081; multiple case reports (e.g., Cheng et al., 2004, PMID: 14749392) |
| Selective 25-hydroxyvitamin D deficiency | Homozygous or compound heterozygous CYP2R1 mutations cause isolated 25-hydroxylase deficiency with normal 1,25-dihydroxyvitamin D levels. | ClinVar; PMID: 14749392 |
| Vitamin D insufficiency (susceptibility) | Common polymorphisms in CYP2R1 (e.g., rs10741657, rs1993116) are associated with lower circulating 25-hydroxyvitamin D levels in genome-wide association studies. | GWAS Catalog; PMID: 20393123 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Testis | 8.2 | Medium |
| Small intestine | 4.1 | Low |
| Kidney | 3.0 | Low |
| Pancreas | 2.5 | Low |
| Adipose tissue | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| Huh-7 | 12.1 | Hepatoma cell line |
| HEK293 | 0.5 | Embryonic kidney cells (low expression) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.296C>T (p.Thr99Met) | Missense | Rare | Loss of enzymatic activity; associated with VDDR1B |
| c.766G>A (p.Glu256Lys) | Missense | Rare | Reduced 25-hydroxylase activity; reported in rickets patients |
| c.1048C>T (p.Arg350Trp) | Missense | Rare | Impaired substrate binding; loss of function |
| rs10741657 (G>A) | Intronic variant | Common (MAF ~0.40) | Associated with lower serum 25-hydroxyvitamin D levels |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Thr99Met, p.Glu256Lys, p.Arg350Trp) reduce or abolish 25-hydroxylase activity, leading to vitamin D deficiency and rickets.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CYP2R1.
Dominant Negative (DN)
No dominant-negative effects have been described; CYP2R1 deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • monooxygenase activity (GO:0004497) | • iron ion binding (GO:0005506) |
| • vitamin D 25-hydroxylase activity (GO:0008392) | • heme binding (GO:0020037) |
| • metal ion binding (GO:0046872) | • oxidation-reduction process (GO:0055114) |
| • vitamin D metabolic process (GO:0060340) |
Pathways
• Vitamin D metabolism (Reactome: R-HSA-196791)
• Metabolism of vitamins and cofactors (Reactome: R-HSA-196854)
• Cytochrome P450 - arranged by substrate type (KEGG: hsa00982)
Protein Summary
CYP2R1 is a 501-amino acid microsomal cytochrome P450 enzyme localized to the endoplasmic reticulum. It contains a conserved heme-binding domain and functions as a vitamin D 25-hydroxylase. The enzyme hydroxylates vitamin D at the C-25 position, producing 25-hydroxyvitamin D, the major circulating form of vitamin D. CYP2R1 is primarily expressed in the liver, with lower levels in testis and other tissues. Its activity is essential for vitamin D activation and calcium homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP2R1 Knockout HEK293 Cell Line | EDJ-KQ7662 | Human | 120227 | Details Get a Quote |
| CYP2R1 Knockout HCT 116 Cell Line | EDJ-KQ33018 | Human | 120227 | Details Get a Quote |
| CYP2R1 Knockout HeLa Cell Line | EDJ-KQ33019 | Human | 120227 | Details Get a Quote |
| CYP2R1 Knockout A-549 Cell Line | EDJ-KQ31686 | Human | 120227 | Details Get a Quote |
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