CYP46A1 cytochrome P450 family 46 subfamily A member 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CYP46A1provided by HGNC
Official Full Name: cytochrome P450 family 46 subfamily A member 1provided by HGNC
Primary source: HGNC:HGNC:2641
See related: Ensembl:ENSG00000036530 MIM:604087; AllianceGenome:HGNC:2641
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]
Expression: Biased expression in brain (RPKM 14.7), heart (RPKM 1.0) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q32.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (99684298..99727301)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (93915741..93958738)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (100150635..100193638)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Cytochrome P450 Family 46 Subfamily A Member 1 Promotes the Progression of Colorectal Cancer by Inducing Tumor Cell Proliferation and Angiogenesis.
Title: Cytochrome P450 Family 46 Subfamily A Member 1 Promotes the Progression of Colorectal Cancer by Inducing Tumor Cell Proliferation and Angiogenesis.
Association of cholesterol 7alpha-hydroxylase (CYP7A1) promoter polymorphism (rs3808607) and cholesterol 24S-hydroxylase (CYP46A1) intron 2 polymorphism (rs754203) with serum lipids, vitamin D levels, and multiple sclerosis risk in the Turkish population.
Title: Association of cholesterol 7α-hydroxylase (CYP7A1) promoter polymorphism (rs3808607) and cholesterol 24S-hydroxylase (CYP46A1) intron 2 polymorphism (rs754203) with serum lipids, vitamin D levels, and multiple sclerosis risk in the Turkish population.
Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma.
Title: Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma.
Identification of CYP46A1 as a new regulator of lipid metabolism through CRISPR-based whole-genome screening.
Title: Identification of CYP46A1 as a new regulator of lipid metabolism through CRISPR-based whole-genome screening.
Polymorphism within the CYP46A1 gene is a positive risk factor for type 2 diabetes mellitus.
Title: The relationship between Multidrug Resistance Protein 1(rs1045642) and Cholesterol 24-hydroxylase (rs754203) genes polymorphism with type 2 diabetes mellitus.
the APOEepsilon4 alleles were significantly higher in patients with Alzheimer's disease (AD) and there was a potential synergistic interaction between the CYP46A1 C allele and APOEepsilon4 allele in AD.
Title: CYP46A1 and the APOEε4 Allele Polymorphisms Correlate with the Risk of Alzheimer's Disease.
Data suggest that CYP46A1, the enzyme responsible for the majority of cholesterol elimination from the brain, exhibits activation by neurotransmitters, L-glutamate, L-aspartate, gamma-aminobutyric acid, and acetylcholine; L-glutamate-induced CYP46A1 activation may be of physiological relevance.
Title: In vitro cytochrome P450 46A1 (CYP46A1) activation by neuroactive compounds.
CYP46A1 rs4900442 genetic polymorphism was associated with increased risk of Alzheimer disease in the Chinese population, but no evidences were detected in Caucasian population.
Title: The association between CYP46A1 rs4900442 polymorphism and the risk of Alzheimer's disease: A meta-analysis.
Findings of this study suggest that CYP46A1 gene and PPARgamma2 gene polymorphisms can be a predictive marker for early identification of population at risk of primary open angle glaucoma (POAG).
Title: Polymorphism of CYP46A1 and PPARγ2 Genes in Risk Prediction of Primary Open Angle Glaucoma Among North Indian Population.

Submit: New GeneRIF Correction See all GeneRIFs (48)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of cytochrome P450, family 46, subfamily A, polypeptide 1 (CYP46A1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78065 (e-PCR)
- UniSTS:5666

D8S2279 (e-PCR)
- UniSTS:473907

sY3084 (e-PCR)
- UniSTS:515126

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

SHGC-81587 (e-PCR)
- UniSTS:103544

PMC22064P1 (e-PCR)
- UniSTS:272092

Gene Ontology Provided by GOA

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	TAS Traceable Author Statement more info
enables heme binding	IBA Inferred from Biological aspect of Ancestor more info
enables heme binding	IDA Inferred from Direct Assay more info	PubMed
enables iron ion binding	IEA Inferred from Electronic Annotation more info
enables steroid hydroxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables testosterone 16-beta-hydroxylase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in bile acid biosynthetic process	TAS Traceable Author Statement more info
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	ISS Inferred from Sequence or Structural Similarity more info
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in progesterone metabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_negative_effect protein localization to membrane raft	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in sterol metabolic process	TAS Traceable Author Statement more info
involved_in xenobiotic metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in postsynapse	ISS Inferred from Sequence or Structural Similarity more info
located_in presynapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: cholesterol 24-hydroxylase

Names: CH24H; cholesterol 24-monooxygenase; cholesterol 24S-hydroxylase; cytochrome P450 46A1; cytochrome P450, family 46, subfamily A, polypeptide 1; cytochrome P450, subfamily 46 (cholesterol 24-hydroxylase)

NP_006659.1

EC 1.14.14.25

XP_005267331.1

EC 1.14.14.25

XP_011534666.1

EC 1.14.14.25

XP_011534667.1

EC 1.14.14.25

XP_016876422.1

EC 1.14.14.25

XP_054231252.1

EC 1.14.14.25

XP_054231253.1

EC 1.14.14.25

XP_054231254.1

EC 1.14.14.25

XP_054231255.1

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.

Genomic

NG_007963.1 RefSeqGene

Range

4881..47884

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_006668.2 → NP_006659.1 cholesterol 24-hydroxylase

See identical proteins and their annotated locations for NP_006659.1

Status: REVIEWED

Source sequence(s)

AF094480, AL160313

Consensus CDS

CCDS9954.1

UniProtKB/Swiss-Prot

B4DHP8, E7EQG9, Q8N2B0, Q9Y6A2

Related

ENSP00000261835.3, ENST00000261835.8

Conserved Domains (1) summary

pfam00067
Location:34 → 466

p450; Cytochrome P450

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

99684298..99727301

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017020933.3 → XP_016876422.1 cholesterol 24-hydroxylase isoform X2
XM_011536364.2 → XP_011534666.1 cholesterol 24-hydroxylase isoform X1

Conserved Domains (1) summary

pfam00067
Location:34 → 456

p450; Cytochrome P450
XM_005267274.6 → XP_005267331.1 cholesterol 24-hydroxylase isoform X3

Conserved Domains (1) summary

cl12078
Location:7 → 321

p450; Cytochrome P450
XM_011536365.3 → XP_011534667.1 cholesterol 24-hydroxylase isoform X4

Conserved Domains (1) summary

cl12078
Location:2 → 313

p450; Cytochrome P450