Cyp46a1 cytochrome P450, family 46, subfamily a, polypeptide 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cyp46a1provided by MGI
Official Full Name: cytochrome P450, family 46, subfamily a, polypeptide 1provided by MGI
Primary source: MGI:MGI:1341877
See related: Ensembl:ENSMUSG00000021259 AllianceGenome:MGI:1341877
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: CH24H; Cyp46
Summary: Enables cholesterol 24-hydroxylase activity. Involved in cholesterol catabolic process and regulation of long-term synaptic potentiation. Acts upstream of with a negative effect on protein localization to membrane raft. Located in several cellular components, including dendrite; endoplasmic reticulum membrane; and postsynapse. Is expressed in several structures, including brain; genitourinary system; liver; retina; and spleen. Human ortholog(s) of this gene implicated in Alzheimer's disease. Orthologous to human CYP46A1 (cytochrome P450 family 46 subfamily A member 1). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in cortex adult (RPKM 70.0), frontal lobe adult (RPKM 59.5) and 7 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 F1; 12 59.41 cM

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (108300568..108328497)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (108334268..108362234)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice.
Title: CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice.
Cholesterol 24-hydroxylase at the choroid plexus contributes to brain immune homeostasis.
Title: Cholesterol 24-hydroxylase at the choroid plexus contributes to brain immune homeostasis.
Cholesterol-24-hydroxylase (CYP46) in the old brain: Analysis of positive populations and factors triggering its expression in astrocytes.
Title: Cholesterol-24-hydroxylase (CYP46) in the old brain: Analysis of positive populations and factors triggering its expression in astrocytes.
Transcription of cytochrome P450 46A1 in NIH3T3 cells is negatively regulated by FBS.
Title: Transcription of cytochrome P450 46A1 in NIH3T3 cells is negatively regulated by FBS.
Brain Acetyl-CoA Production and Phosphorylation of Cytoskeletal Proteins Are Targets of CYP46A1 Activity Modulation and Altered Sterol Flux.
Title: Brain Acetyl-CoA Production and Phosphorylation of Cytoskeletal Proteins Are Targets of CYP46A1 Activity Modulation and Altered Sterol Flux.
Collectively, the data obtained establish metabolic and regulatory significance of CYP46A1 for the retina and suggest pharmacologic activation of CYP46A1 as a potential therapeutic approach to dyslipidemia-induced retinal damage.
Title: Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in Cytochrome P450 46A1-Mediated Cholesterol Removal.
Enhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal hypoxia-ischemia
Title: Upregulation of cholesterol 24-hydroxylase following hypoxia-ischemia in neonatal mouse brain.
Oral administration of a small dose of the anti-HIV drug efavirenz to a mouse model of Alzheimer's disease ameliorated amyloid pathology in the brain and led to changes supporting therapeutic potential of cholesterol-metabolizing enzyme CYP46A1, its metabolite 24HC and 24HC-mediated liver X receptors transrepression of some of the inflammatory genes in astrocytes and microglia surrounding amyloid plaques.
Title: Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease.
The present study demonstrates the diverse potential effects of CYP46A1 deficiency on brain functions and identifies important proteins that could be affected by this deficiency
Title: Transcriptional and post-translational changes in the brain of mice deficient in cholesterol removal mediated by cytochrome P450 46A1 (CYP46A1).
Increased expression of CYP46A1 in the striatum decreased neuronal atrophy in a Huntington's disease model.
Title: CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington's disease.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Targeted (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Cyp46a1 (e-PCR), detects polymorphism
- UniSTS:498288

Cyp46a1 (e-PCR), detects polymorphism
- UniSTS:463005

MARC_11469-11470:1000829919:1 (e-PCR)
- UniSTS:267196

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cholesterol 24-hydroxylase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cholesterol 24-hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables cholesterol 24-hydroxylase activity	ISO Inferred from Sequence Orthology more info
enables cholesterol 24-hydroxylase activity	ISS Inferred from Sequence or Structural Similarity more info
enables heme binding	IBA Inferred from Biological aspect of Ancestor more info
enables heme binding	ISO Inferred from Sequence Orthology more info
enables heme binding	ISS Inferred from Sequence or Structural Similarity more info
enables iron ion binding	IEA Inferred from Electronic Annotation more info
enables steroid hydroxylase activity	ISO Inferred from Sequence Orthology more info
enables steroid hydroxylase activity	ISS Inferred from Sequence or Structural Similarity more info
enables testosterone 16-beta-hydroxylase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cholesterol catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol catabolic process	IEA Inferred from Electronic Annotation more info
involved_in cholesterol catabolic process	ISO Inferred from Sequence Orthology more info
involved_in cholesterol catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in progesterone metabolic process	ISO Inferred from Sequence Orthology more info
involved_in progesterone metabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_negative_effect protein localization to membrane raft	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in xenobiotic metabolic process	ISO Inferred from Sequence Orthology more info
involved_in xenobiotic metabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in postsynapse	IDA Inferred from Direct Assay more info	PubMed
located_in presynapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cholesterol 24-hydroxylase

Names: cholesterol 24-monooxygenase; cholesterol 24S-hydroxylase; cholestrol 24-hydroxylase; cytochrome P450, 46a1 (cholesterol 24-hydroxylase)

NP_034140.1

EC 1.14.14.25

XP_030102395.1

EC 1.14.14.25

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_010010.3 → NP_034140.1 cholesterol 24-hydroxylase

See identical proteins and their annotated locations for NP_034140.1

Status: VALIDATED

Source sequence(s)

AF094479, BY238426

Consensus CDS

CCDS26160.1

UniProtKB/Swiss-Prot

Q9WVK8

UniProtKB/TrEMBL

Q3US73

Related

ENSMUSP00000021684.5, ENSMUST00000021684.6

Conserved Domains (1) summary

pfam00067
Location:34 → 466

p450; Cytochrome P450

RNA

NR_176848.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC154910

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000078.7 Reference GRCm39 C57BL/6J

Range

108300568..108328497

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030246535.2 → XP_030102395.1 cholesterol 24-hydroxylase isoform X1

Conserved Domains (1) summary

cl12078
Location:27 → 234

p450; Cytochrome P450