CYP7A1 (Cholesterol 7-alpha-hydroxylase) Gene
Key enzyme in bile acid synthesis and cholesterol homeostasis; genetic variants linked to hypercholesterolemia and gallstone disease.
Gene Information Card
| Symbol | CYP7A1 |
|---|---|
| Full Name | Cytochrome P450 family 7 subfamily A member 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 8q12.1 |
| NCBI Gene ID | 1581 ncbi.nlm.nih.gov/gene/1581 |
| Ensembl ID | ENSG00000167910 |
| UniProt ID | P22680 |
| OMIM ID | 118455 |
| HGNC ID | 2606 |
| Aliases | CYP7A, cholesterol 7-alpha-hydroxylase |
Description
The CYP7A1 gene encodes cholesterol 7-alpha-hydroxylase, a cytochrome P450 enzyme that catalyzes the rate-limiting step in the classic bile acid synthesis pathway. This enzyme converts cholesterol to 7-alpha-hydroxycholesterol, initiating bile acid production in the liver. CYP7A1 is critical for cholesterol homeostasis, as bile acid synthesis is a major route for eliminating cholesterol from the body. Regulation of CYP7A1 expression is tightly controlled by nuclear receptors (e.g., FXR, LXR) and hormones. Genetic variations in CYP7A1 can affect enzyme activity, influencing lipid metabolism and susceptibility to metabolic diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypercholesterolemia | Loss-of-function variants reduce bile acid synthesis, leading to decreased cholesterol clearance and elevated plasma LDL cholesterol. | ClinVar and literature (e.g., Pullinger et al., 2002) report associations with high LDL levels. |
| Gallstone disease | Reduced CYP7A1 activity alters bile acid composition, increasing cholesterol saturation in bile and promoting gallstone formation. | Genetic association studies (e.g., Wang et al., 2018) link CYP7A1 SNPs to gallstone risk. |
| Cerebrotendinous xanthomatosis (CTX) | While CTX is primarily due to CYP27A1 mutations, CYP7A1 variants may modify bile acid synthesis and exacerbate lipid abnormalities. | Case reports suggest potential modifier effects, but direct evidence is limited. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | ~50 | High expression; primary site of bile acid synthesis. |
| Small intestine | ~1 | Low expression; minor role in enterohepatic circulation. |
| Kidney | ~0.5 | Very low expression; not significant. |
| Other tissues | 0 | No significant expression detected. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | ~30 | Hepatocellular carcinoma cell line; expresses CYP7A1 at moderate levels. |
| Huh7 | ~20 | Hepatoma cell line; lower expression compared to HepG2. |
| Primary hepatocytes | ~50 | High expression; used for functional studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3808607 | SNP (promoter) | ~30% allele frequency | May affect gene expression; associated with altered LDL cholesterol levels. |
| rs8192875 | Missense (p.Arg367Cys) | Rare (<1%) | Reduced enzyme activity in vitro; linked to hypercholesterolemia. |
| rs8192876 | Missense (p.Leu408Phe) | Rare (<1%) | Impaired catalytic function; potential impact on bile acid synthesis. |
Mutation functional classification
Loss of Function (LOF)
Variants such as p.Arg367Cys and p.Leu408Phe reduce or abolish enzyme activity, leading to decreased bile acid production and elevated cholesterol levels.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; increased activity is typically due to upregulation by LXR agonists, not genetic variants.
Dominant Negative (DN)
No evidence for dominant-negative effects; CYP7A1 is a monomeric enzyme, and haploinsufficiency is the likely mechanism for loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • cholesterol 7-alpha-monooxygenase activity | • iron ion binding |
| • heme binding | • oxidoreductase activity |
| • acting on paired donors | • with incorporation or reduction of molecular oxygen |
| • monooxygenase activity | • lipid metabolic process |
| • bile acid biosynthetic process | • cholesterol metabolic process |
| • response to nutrient levels |
Pathways
• Bile acid biosynthesis (classic pathway)
• Cholesterol metabolism
• Metabolism of lipids and lipoproteins
Protein Summary
Cholesterol 7-alpha-hydroxylase (CYP7A1) is a 504-amino acid microsomal cytochrome P450 enzyme predominantly expressed in the liver. It catalyzes the first and rate-limiting step in the classic bile acid synthesis pathway, converting cholesterol to 7-alpha-hydroxycholesterol. The protein contains a heme-binding domain and a conserved P450 cysteine ligand. Its activity is regulated at the transcriptional level by bile acids (via FXR), oxysterols (via LXR), and hormones (e.g., insulin, thyroid hormone). Post-translational regulation includes phosphorylation and ubiquitin-mediated degradation. CYP7A1 is essential for maintaining cholesterol balance; deficiency leads to hypercholesterolemia and increased risk of gallstones.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP7A1 Knockout HEK293 Cell Line | EDJ-KQ3904 | Human | 1581 | Details Get a Quote |
| CYP7A1 Knockout HeLa Cell Line | EDJ-KQ53056 | Human | 1581 | Details Get a Quote |
| CYP7A1 Knockout A-549 Cell Line | EDJ-KQ61521 | Human | 1581 | Details Get a Quote |
| CYP7A1 Knockout HCT 116 Cell Line | EDJ-KQ70013 | Human | 1581 | Details Get a Quote |
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