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    CYP46A1 cytochrome P450, family 46, subfamily A, polypeptide 1 [ Homo sapiens ]

    Gene ID: 10858, updated on 5-Feb-2012
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    Summary

    Official Symbol
    CYP46A1provided by HGNC
    Official Full Name
    cytochrome P450, family 46, subfamily A, polypeptide 1provided by HGNC
    Primary source
    HGNC:2641
    See related
    Ensembl:ENSG00000036530; HPRD:04970; MIM:604087; Vega:OTTHUMG00000171510
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CP46; CYP46
    Summary
    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. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    14q32.1
    Sequence :
    Chromosome: 14; NC_000014.8 (100150755..100193638)
    See CYP46A1 in Epigenomics, MapViewer

    Chromosome 14 - NC_000014.8Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100507108 Neighboring gene HHIP-like 1 Neighboring gene echinoderm microtubule associated protein like 1 Neighboring gene voltage-dependent anion channel 3 pseudogene 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma. Mossböck G, et al. Mol Vis, 2011 Feb 26. PMID 21386929.
    2. Quantification of cholesterol-metabolizing P450s CYP27A1 and CYP46A1 in neural tissues reveals a lack of enzyme-product correlations in human retina but not human brain. Liao WL, et al. J Proteome Res, 2011 Jan 7. PMID 21049985.
    3. CYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's disease. Li Y, et al. J Alzheimers Dis, 2010. PMID 20693622.
    4. A pilot study of gene/gene and gene/environment interactions in Alzheimer disease. Ghebranious N, et al. Clin Med Res, 2011 Mar. PMID 20682755.
    5. Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain. Mast N, et al. J Biol Chem, 2010 Oct 8. PMID 20667828.

    See all (48) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. The data of this study suggested that CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects.
      Title: A CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects.
    2. The rs754203 polymorphism itself is unlikely a genetic risk factor for primary open angle glaucoma in Caucasian individuals.
      Title: Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.
    3. The average P450 concentrations/mg of total tissue protein were 345 fmol of CYP46A1 and 110 fmol of CYP27A1 in the temporal lobe, and 60 fmol of CYP46A1 and 490 fmol of CYP27A1 in the retina.
      Title: Quantification of cholesterol-metabolizing P450s CYP27A1 and CYP46A1 in neural tissues reveals a lack of enzyme-product correlations in human retina but not human brain.
    4. Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain.
      Title: Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain.
    5. Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator)
      Title: A pilot study of gene/gene and gene/environment interactions in Alzheimer disease.
    6. Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons
      Title: Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study.
    7. These results suggest that a disturbance of cholesterol metabolism may contribute to loss of EAAT2 in AD.
      Title: Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer's disease.
    8. The rs754203 SNP in CYP46A1 was associated with a risk for POAG. This polymorphism was not associated with changes in plasma 24S-hydroxycholesterol.
      Title: Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels.
    9. From the logistic regression ananlsis of this stidy showed that the highest risk for was found for Alzheimer's disease individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele.
      Title: Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes.
    10. the substrate, cholesterol, enters CYP46A1 from the membrane
      Title: Combined use of mass spectrometry and heterologous expression for identification of membrane-interacting peptides in cytochrome P450 46A1 and NADPH-cytochrome P450 oxidoreductase.
    Submit: New GeneRIF Correction See all (24)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Bile acid and bile salt metabolism, organism-specific biosystem (from REACTOME)
      Bile acid and bile salt metabolism, organism-specific biosystemIn a healthy adult human, about 500 mg of cholesterol is converted to bile salts daily. Newly synthesized bile salts are secreted into the bile and released into the small intestine where they emulsi...
    • Biological oxidations, organism-specific biosystem (from REACTOME)
      Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
    • Cytochrome P450 - arranged by substrate type, organism-specific biosystem (from REACTOME)
      Cytochrome P450 - arranged by substrate type, organism-specific biosystemThe P450 isozyme system is the major phase 1 biotransforming system in man, accounting for more than 90% of drug biotransformations. This system has huge catalytic versatility and a broad substrate s...
    • Endogenous sterols, organism-specific biosystem (from REACTOME)
      Endogenous sterols, organism-specific biosystemA number of CYPs take part in cholesterol biosynthesis and elimination, thus playing an important role in maintaining cholesterol homeostasis. Under normal physiological conditions, cholesterol intak...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • Phase 1 - Functionalization of compounds, organism-specific biosystem (from REACTOME)
      Phase 1 - Functionalization of compounds, organism-specific biosystemPhase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conj...
    • Primary bile acid biosynthesis, organism-specific biosystem (from KEGG)
      Primary bile acid biosynthesis, organism-specific biosystemBile acids are steroid carboxylic acids derived from cholesterol in vertebrates. The primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the liver and conjugated with taurin...
    • Primary bile acid biosynthesis, conserved biosystem (from KEGG)
      Primary bile acid biosynthesis, conserved biosystemBile acids are steroid carboxylic acids derived from cholesterol in vertebrates. The primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the liver and conjugated with taurin...
    • Synthesis of bile acids and bile salts, organism-specific biosystem (from REACTOME)
      Synthesis of bile acids and bile salts, organism-specific biosystemIn a healthy adult human, about 500 mg of cholesterol is converted to bile salts daily (Russell 2003). The major pathway for bile salt synthesis in the liver begins with the conversion of cholesterol...
    • Synthesis of bile acids and bile salts via 24-hydroxycholesterol, organism-specific biosystem (from REACTOME)
      Synthesis of bile acids and bile salts via 24-hydroxycholesterol, organism-specific biosystemIn the body, 24-hydroxycholesterol is synthesized in the brain, exported to the liver, and converted there to bile acids and bile salts. This pathway is only a minor source of bile acids and bile sal...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cholesterol 24-hydroxylase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    electron carrier activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    heme binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    monooxygenase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen IEA
    Inferred from Electronic Annotation
    more info
    		  
    steroid hydroxylase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    bile acid biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    bile acid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    cholesterol catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    nervous system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
    		  
    xenobiotic metabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    microsome IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    cholesterol 24-hydroxylase
    Names
    cholesterol 24-hydroxylase
    CH24H
    cytochrome P450 46A1
    cytochrome P450, subfamily 46 (cholesterol 24-hydroxylase)
    NP_006659.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007963.1 RefSeqGene

      Range
      5001..47884
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006668.1 → NP_006659.1  cholesterol 24-hydroxylase precursor

      Status: REVIEWED

      Source sequence(s)
      AF094480
      Consensus CDS
      CCDS9954.1
      UniProtKB/Swiss-Prot
      Q9Y6A2
      Related
      ENSP00000261835, OTTHUMP00000246265, ENST00000261835, OTTHUMT00000413814
      Conserved Domains (2) summary
      pfam00067
      Location:34 – 466
      Blast Score: 649
      p450; Cytochrome P450
      cl12078
      Location:52 – 489
      Blast Score: 497
      CypX; Cytochrome P450 [Secondary metabolites biosynthesis, transport, and catabolism]

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000014.8 Reference GRCh37.p5 Primary Assembly

      Range
      100150755..100193638
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000146.1 Alternate HuRef

      Range
      80333998..80376909
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL136000.4 (9830..27432) None
    genomic AL160313.4 (1992..27272) None
    genomic CH471061.1 EAW81678.1
    mRNA AB209749.1 BAD92986.1
    mRNA AF094480.1 AAD41244.1
    mRNA AK090886.1 BAC03539.1
    mRNA AK295216.1 BAG58210.1
    mRNA BC022539.1 AAH22539.1
    Protein Accession Links
    GenePept Link UniProtKB Link
    Q59ER2 GenPept UniProtKB/TrEMBL:Q59ER2
    Q8N2B0 GenPept UniProtKB/TrEMBL:Q8N2B0
    Q9Y6A2.1 GenPept UniProtKB/Swiss-Prot:Q9Y6A2
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

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