CYP46A1

Cytochrome P450, family 46, subfamily A, polypeptide 1
Rendering based on PDB 2Q9F​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2Q9F​, 2Q9G​, 3MDM​, 3MDR​, 3MDT​, 3MDV​, 4ENH​, 4FIA​, 4J14​
Identifiers
Symbols	CYP46A1 ; CP46; CYP46
External IDs	OMIM: 604087 MGI: 1341877 HomoloGene: 134501 IUPHAR: 1373 GeneCards: CYP46A1 Gene
EC number	1.14.13.98
Gene ontology Molecular function • iron ion binding • steroid hydroxylase activity • heme binding • cholesterol 24-hydroxylase activity Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • integral component of membrane Biological process • bile acid biosynthetic process • cholesterol catabolic process • xenobiotic metabolic process • nervous system development • bile acid metabolic process • sterol metabolic process • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10858	13116
Ensembl	ENSG00000036530	ENSMUSG00000021259
UniProt	Q9Y6A2	Q9WVK8
RefSeq (mRNA)	NM_006668	NM_010010
RefSeq (protein)	NP_006659	NP_034140
Location (UCSC)	Chr 14: 99.68 – 99.73 Mb	Chr 12: 108.33 – 108.36 Mb
PubMed search

Cholesterol 24-hydroxylase is an enzyme that in humans is encoded by the CYP46A1 gene.^[1][2]

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein is expressed in the brain, where it converts cholesterol to 24S-hydroxycholesterol. While cholesterol cannot pass the blood–brain barrier, 24S-hydroxycholesterol can be secreted in the brain into the circulation to be returned to the liver for catabolism.^[2]

References

1. Lund EG, Guileyardo JM, Russell DW (Jul 1999). "cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain". Proc Natl Acad Sci U S A 96 (13): 7238–43. doi:10.1073/pnas.96.13.7238. PMC 22064. PMID 10377398.
2. "Entrez Gene: CYP46A1 cytochrome P450, family 46, subfamily A, polypeptide 1".

Further reading

• Russell DW (2001). "Oxysterol biosynthetic enzymes.". Biochim. Biophys. Acta 1529 (1–3): 126–35. doi:10.1016/S1388-1981(00)00142-6. PMID 11111082.
• Wolozin B (2003). "Cyp46 (24S-cholesterol hydroxylase): a genetic risk factor for Alzheimer disease". Arch. Neurol. 60 (1): 16–8. doi:10.1001/archneur.60.1.16. PMID 12533083.
• Björkhem I, Lütjohann D, Diczfalusy U; et al. (1998). "Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation". J. Lipid Res. 39 (8): 1594–600. PMID 9717719.
• Bogdanovic N, Bretillon L, Lund EG; et al. (2002). "On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells". Neurosci. Lett. 314 (1–2): 45–8. doi:10.1016/S0304-3940(01)02277-7. PMID 11698143.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Papassotiropoulos A, Streffer JR, Tsolaki M; et al. (2003). "Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism". Arch. Neurol. 60 (1): 29–35. doi:10.1001/archneur.60.1.29. PMID 12533085.
• Mast N, Norcross R, Andersson U; et al. (2004). "Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain". Biochemistry 42 (48): 14284–92. doi:10.1021/bi035512f. PMID 14640697.
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Chalmers KA, Culpan D, Kehoe PG; et al. (2004). "APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease". NeuroReport 15 (1): 95–8. doi:10.1097/00001756-200401190-00019. PMID 15106838.
• Borroni B, Archetti S, Agosti C; et al. (2004). "Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators". Neurobiol. Aging 25 (6): 747–51. doi:10.1016/j.neurobiolaging.2003.08.004. PMID 15165699.
• Kabbara A, Payet N, Cottel D; et al. (2004). "Exclusion of CYP46 and APOM as candidate genes for Alzheimer's disease in a French population". Neurosci. Lett. 363 (2): 139–43. doi:10.1016/j.neulet.2004.03.066. PMID 15172102.
• Wang B, Zhang C, Zheng W; et al. (2004). "Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase gene and Alzheimer's disease in Chinese". Neurosci. Lett. 369 (2): 104–7. doi:10.1016/j.neulet.2004.07.020. PMID 15450677.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Golanska E, Hulas-Bigoszewska K, Wojcik I; et al. (2005). "CYP46: a risk factor for Alzheimer's disease or a coincidence?". Neurosci. Lett. 383 (1–2): 105–8. doi:10.1016/j.neulet.2005.03.049. PMID 15936520.
• Shibata N, Kawarai T, Lee JH; et al. (2006). "Association studies of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer's disease". Neurosci. Lett. 391 (3): 142–6. doi:10.1016/j.neulet.2005.08.048. PMID 16157450.
• Ma SL, Tang NL, Lam LC, Chiu HF (2006). "Polymorphisms of the cholesterol 24-hydroxylase (CYP46A1) gene and the risk of Alzheimer's disease in a Chinese population". International psychogeriatrics / IPA 18 (1): 37–45. doi:10.1017/S1041610205003108. PMID 16734927.
• Wang F, Jia J (2007). "Polymorphisms of cholesterol metabolism genes CYP46 and ABCA1 and the risk of sporadic Alzheimer's disease in Chinese". Brain Res. 1147: 34–8. doi:10.1016/j.brainres.2007.02.005. PMID 17335784.