CYP46A1
Cytochrome P450 Family 46 Subfamily A Member 1
Gene Information Card
| Symbol | CYP46A1 |
|---|---|
| Full Name | Cytochrome P450 Family 46 Subfamily A Member 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 10858 ncbi.nlm.nih.gov/gene/10858 |
| Ensembl ID | ENSG00000136535 |
| UniProt ID | Q9Y6A2 |
| OMIM ID | 604087 |
| HGNC ID | 2641 |
| Aliases | CP46, CYP46, P450-24, CH24H |
Description
CYP46A1 encodes cholesterol 24-hydroxylase, a cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol to 24S-hydroxycholesterol, the primary pathway for cholesterol elimination from the brain. This enzyme is predominantly expressed in neurons and plays a critical role in maintaining brain cholesterol homeostasis. Dysregulation of CYP46A1 has been implicated in neurodegenerative disorders, including Alzheimer disease and cognitive decline.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Reduced CYP46A1 activity leads to cholesterol accumulation in neurons, promoting amyloid-beta production and tau pathology. | ClinVar, OMIM |
| Cognitive impairment | Loss-of-function variants impair cholesterol clearance, associated with synaptic dysfunction and memory deficits. | NCBI Gene, PubMed |
| Huntington disease | Altered CYP46A1 expression contributes to disrupted cholesterol metabolism in striatal neurons. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Liver | 0.2 | Not detected |
| Kidney | 0.1 | Not detected |
| Heart | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.3 | Neuronal cell line |
| U-87 MG | 8.7 | Glioblastoma cell line |
| HEK293 | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1075C>T (p.Arg359Trp) | Missense | <0.01% | Reduced enzymatic activity; associated with Alzheimer disease risk |
| c.1243G>A (p.Val415Met) | Missense | <0.01% | Decreased cholesterol 24-hydroxylase activity |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg359Trp) reduce cholesterol 24-hydroxylase activity, impairing brain cholesterol clearance.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cholesterol metabolism (Reactome: R-HSA-191273)
• Metabolism of lipids (Reactome: R-HSA-556833)
Protein Summary
Cholesterol 24-hydroxylase is a 500-amino-acid microsomal cytochrome P450 enzyme localized to the endoplasmic reticulum. It contains a heme-binding domain and utilizes NADPH-cytochrome P450 reductase to convert cholesterol to 24S-hydroxycholesterol, which can cross the blood-brain barrier. This enzyme is essential for brain cholesterol efflux and is regulated by sterol regulatory element-binding proteins (SREBPs).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP46A1 Knockout HEK293 Cell Line | EDJ-KQ2349 | Human | 10858 | Details Get a Quote |
| CYP46A1 Knockout HeLa Cell Line | EDJ-KQ55500 | Human | 10858 | Details Get a Quote |
| CYP46A1 Knockout A-549 Cell Line | EDJ-KQ63989 | Human | 10858 | Details Get a Quote |
| CYP46A1 Knockout HCT 116 Cell Line | EDJ-KQ72441 | Human | 10858 | Details Get a Quote |
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