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CYP46A1 Gene(Protein Coding)

Cytochrome P450 Family 46 Subfamily A Member 1

GCID:
GC14P099684
GIFtS:
51
Genes Participants
UDN Logo

Aliases for CYP46A1 Gene

Aliases for CYP46A1 Gene

  • Cytochrome P450 Family 46 Subfamily A Member 1 2 3 5
  • Cytochrome P450, Subfamily 46 (Cholesterol 24-Hydroxylase) 2 3
  • Cytochrome P450, Family 46, Subfamily A, Polypeptide 1 2 3
  • Cytochrome P450 46A1 3 4
  • CYP46 3 4
  • CH24H 3 4
  • Cholesterol 24-Hydroxylase 3
  • EC 1.14.14.25 4
  • CP46 3

External Ids for CYP46A1 Gene

Previous HGNC Symbols for CYP46A1 Gene

  • CYP46

Previous GeneCards Identifiers for CYP46A1 Gene

  • GC14P093966
  • GC14P098140
  • GC14P099220
  • GC14P100150
  • GC14P080333

Summaries for CYP46A1 Gene

Entrez Gene Summary for CYP46A1 Gene

  • 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]

GeneCards Summary for CYP46A1 Gene

CYP46A1 (Cytochrome P450 Family 46 Subfamily A Member 1) is a Protein Coding gene. Diseases associated with CYP46A1 include Anus Disease and Alpha-Methylacyl-Coa Racemase Deficiency. Among its related pathways are Metabolism and Cytochrome P450 - arranged by substrate type. Gene Ontology (GO) annotations related to this gene include iron ion binding and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. An important paralog of this gene is CYP3A4.

UniProtKB/Swiss-Prot for CYP46A1 Gene

  • Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. Has also activity with xenobiotic compounds, such as clotrimazole.

Gene Wiki entry for CYP46A1 Gene

Additional gene information for CYP46A1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CYP46A1 Gene

Genomics for CYP46A1 Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for CYP46A1 Gene

Promoters and enhancers for CYP46A1 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH14I099682 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 550.8 -0.4 -405 2.3 ARID4B SIN3A ZNF2 ZBTB7B ZNF213 E2F8 ZNF207 ZNF143 KLF13 SP3 CYP46A1 HHIPL1 ENSG00000258672 GC14P099668
GH14I099872 Enhancer 0.7 ENCODE 10.7 +188.5 188452 1.4 MZF1 FEZF1 ZIC2 ZNF2 ZNF213 RCOR1 EZH2 ZNF10 GFI1B ZBTB8A EML1 CCNK ENSG00000234648 RPL3P4 CYP46A1 GC14M099882 GC14M099754
GH14I099277 Enhancer 0.6 FANTOM5 dbSUPER 12.1 -406.5 -406450 0.3 PRDM10 GC14P099279 CYP46A1 BCL11B
GH14I099819 Enhancer 0.4 dbSUPER 10.7 +135.8 135760 1.8 MAZ ZNF341 PRDM1 EML1 HHIPL1 CYP46A1 GC14M099754 GC14M099882
GH14I099822 Enhancer 0.4 ENCODE dbSUPER 10.6 +138.7 138707 0.9 EML1 HHIPL1 CYP46A1 GC14M099754 GC14M099882
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CYP46A1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CYP46A1 gene promoter:

Genomic Locations for CYP46A1 Gene

Genomic Locations for CYP46A1 Gene
chr14:99,684,262-99,727,321
(GRCh38/hg38)
Size:
43,060 bases
Orientation:
Plus strand
chr14:100,150,641-100,193,638
(GRCh37/hg19)

Genomic View for CYP46A1 Gene

Genes around CYP46A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CYP46A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CYP46A1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CYP46A1 Gene

Proteins for CYP46A1 Gene

Products:

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  • Protein details for CYP46A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6A2-CP46A_HUMAN
    Recommended name:
    Cholesterol 24-hydroxylase
    Protein Accession:
    Q9Y6A2
    Secondary Accessions:
    • B4DHP8
    • E7EQG9
    • Q8N2B0

    Protein attributes for CYP46A1 Gene

    Size:
    500 amino acids
    Molecular mass:
    56821 Da
    Cofactor:
    Name=heme; Xref=ChEBI:CHEBI:30413;
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for CYP46A1 Gene

    Alternative splice isoforms for CYP46A1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CYP46A1 Gene

Protein Expression for CYP46A1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for CYP46A1 Gene

No Post-translational modifications

Other Protein References for CYP46A1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CYP46A1 Gene

Domains & Families for CYP46A1 Gene

Gene Families for CYP46A1 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for CYP46A1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CYP46A1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y6A2

UniProtKB/Swiss-Prot:

CP46A_HUMAN :
  • Belongs to the cytochrome P450 family.
Family:
  • Belongs to the cytochrome P450 family.
genes like me logo Genes that share domains with CYP46A1: view

Function for CYP46A1 Gene

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  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for CYP46A1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=2.2 uM for 24(S)-hydroxycholesterol {ECO:0000269 PubMed:14640697};
UniProtKB/Swiss-Prot CatalyticActivity:
Cholesterol + [reduced NADPH--hemoprotein reductase] + O(2) = (24S)-cholest-5-ene-3-beta,24-diol + [oxidized NADPH--hemoprotein reductase] + H(2)O.
UniProtKB/Swiss-Prot Function:
Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. Has also activity with xenobiotic compounds, such as clotrimazole.

Enzyme Numbers (IUBMB) for CYP46A1 Gene

Phenotypes From GWAS Catalog for CYP46A1 Gene

Gene Ontology (GO) - Molecular Function for CYP46A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005506 iron ion binding IEA --
GO:0008395 steroid hydroxylase activity TAS 10377398
GO:0016491 oxidoreductase activity IEA --
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen IEA --
GO:0020037 heme binding IDA,IEA 18621681
genes like me logo Genes that share ontologies with CYP46A1: view
genes like me logo Genes that share phenotypes with CYP46A1: view

Animal Models for CYP46A1 Gene

MGI Knock Outs for CYP46A1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CYP46A1 Gene

Localization for CYP46A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CYP46A1 Gene

Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CYP46A1 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 2
golgi apparatus 2
extracellular 1

Gene Ontology (GO) - Cellular Components for CYP46A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum TAS 10377398
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0031090 organelle membrane IEA --
genes like me logo Genes that share ontologies with CYP46A1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CYP46A1 Gene

Pathways & Interactions for CYP46A1 Gene

genes like me logo Genes that share pathways with CYP46A1: view

Pathways by source for CYP46A1 Gene

2 BioSystems pathways for CYP46A1 Gene
1 KEGG pathway for CYP46A1 Gene

Gene Ontology (GO) - Biological Process for CYP46A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006699 bile acid biosynthetic process TAS --
GO:0006707 cholesterol catabolic process TAS,IDA 18621681
GO:0006805 xenobiotic metabolic process IDA 20667828
GO:0007399 nervous system development TAS 10377398
genes like me logo Genes that share ontologies with CYP46A1: view

No data available for SIGNOR curated interactions for CYP46A1 Gene

Drugs & Compounds for CYP46A1 Gene

Products:

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(5) Drugs for CYP46A1 Gene - From: DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cholesterol Approved, Experimental, Investigational Pharma Agonist 0
Oxygen Approved, Vet_approved Pharma 0
Water Approved Pharma 0
RC-8800 Pharma 0
heme Pharma Agonist 0

(5) Additional Compounds for CYP46A1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
24-Hydroxycholesterol
  • (24S)-24-Hydroxycholesterol
  • (24S)-cholest-5-ene-3b,24-diol
  • (24S)-cholest-5-ene-3beta,24-diol
  • 24(S)-Hydroxycholesterol
  • 24-Hydroxycholesterol
 474-73-7
NADP
  • Adenine-nicotinamide dinucleotide phosphate
  • b-NADP
  • b-Nicotinamide adenine dinucleotide phosphate
  • b-TPN
  • beta-NADP
 53-59-8
nadph
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosylnicotinamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-D-ribofuranosyl-3-pyridinecarboxamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosyl-3-pyridinecarboxamide
  • b-NADPH
 53-57-6
genes like me logo Genes that share compounds with CYP46A1: view

Transcripts for CYP46A1 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for CYP46A1 Gene

(5) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(31) Selected AceView cDNA sequences:
(7) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CYP46A1 Gene

Cytochrome P450, family 46, subfamily A, polypeptide 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for CYP46A1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15
SP1: -
SP2: -

Relevant External Links for CYP46A1 Gene

GeneLoc Exon Structure for
CYP46A1
ECgene alternative splicing isoforms for
CYP46A1

Expression for CYP46A1 Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CYP46A1 Gene

mRNA expression in normal human tissues for CYP46A1 Gene
mRNA expression by GTEx for CYP46A1 GenemRNA expression by BioGPS for CYP46A1 Gene

mRNA differential expression in normal tissues according to GTEx for CYP46A1 Gene

This gene is overexpressed in Brain - Putamen (basal ganglia) (x9.1), Brain - Nucleus accumbens (basal ganglia) (x8.0), Brain - Caudate (basal ganglia) (x7.8), and Brain - Cortex (x4.8).

Protein differential expression in normal tissues from HIPED for CYP46A1 Gene

This gene is overexpressed in Heart (45.3), Frontal cortex (11.8), and Fetal Brain (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for CYP46A1 Gene



Protein tissue co-expression partners for CYP46A1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CYP46A1 Gene:

CYP46A1

SOURCE GeneReport for Unigene cluster for CYP46A1 Gene:

Hs.25121

mRNA Expression by UniProt/SwissProt for CYP46A1 Gene:

Q9Y6A2-CP46A_HUMAN
Tissue specificity: Expressed in brain. The mRNA was broadly distributed with higher levels in gray matter zones and lower levels in regions rich in white matter. Not detected in fetal sample but its expression increases linearly with age.

Evidence on tissue expression from TISSUES for CYP46A1 Gene

  • Nervous system(4.6)
genes like me logo Genes that share expression patterns with CYP46A1: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CYP46A1 Gene

Orthologs for CYP46A1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CYP46A1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia CYP46A1 33 34
  • 99.59 (n)
cow
(Bos Taurus)
 Mammalia CYP46A1 33 34
  • 90.33 (n)
dog
(Canis familiaris)
 Mammalia CYP46A1 33 34
  • 90.12 (n)
mouse
(Mus musculus)
 Mammalia Cyp46a1 33 16 34
  • 89.6 (n)
rat
(Rattus norvegicus)
 Mammalia Cyp46a1 33
  • 88.83 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia CYP46A1 34
  • 56 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves CYP46A1 33 34
  • 66.52 (n)
lizard
(Anolis carolinensis)
 Reptilia -- 34
  • 53 (a)
 OneToMany
-- 34
  • 51 (a)
 OneToMany
tropical clawed frog
(Silurana tropicalis)
 Amphibia mgc108213 33
  • 59.04 (n)
African clawed frog
(Xenopus laevis)
 Amphibia MGC64404 33
zebrafish
(Danio rerio)
 Actinopterygii cyp46a4 34
  • 48 (a)
 OneToMany
cyp46a1 34
  • 47 (a)
 OneToMany
cyp46a2 34
  • 47 (a)
 OneToMany
CYP46A1 (4 of 5) 34
  • 44 (a)
 OneToMany
CYP46A1 (5 of 5) 34
  • 39 (a)
 OneToMany
zgc63602 33
rainbow trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.48 33
fruit fly
(Drosophila melanogaster)
 Insecta Cyp310a1 34
  • 18 (a)
 OneToMany
thale cress
(Arabidopsis thaliana)
 eudicotyledons CYP97A3 33
  • 40.64 (n)
rice
(Oryza sativa)
 Liliopsida Os02g0817900 33
  • 44.22 (n)
Species where no ortholog for CYP46A1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CYP46A1 Gene

ENSEMBL:
Gene Tree for CYP46A1 (if available)
TreeFam:
Gene Tree for CYP46A1 (if available)

Paralogs for CYP46A1 Gene

Paralogs for CYP46A1 Gene

(3) SIMAP similar genes for CYP46A1 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for CYP46A1 Gene

genes like me logo Genes that share paralogs with CYP46A1: view

Variants for CYP46A1 Gene

Sequence variations from dbSNP and Humsavar for CYP46A1 Gene

SNP ID Clin Chr 14 pos Variation AA Info Type
rs1000000792 -- 99,701,376(+) A/G genic_upstream_transcript_variant, intron_variant
rs1000210437 -- 99,719,748(+) TTTTTTTT/TTTTTTT/TTTTTTTTT intron_variant
rs1000264443 -- 99,699,227(+) C/A/T genic_upstream_transcript_variant, intron_variant
rs1000302677 -- 99,725,922(+) G/A intron_variant
rs1000308057 -- 99,688,244(+) A/G genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CYP46A1 Gene

Variant ID Type Subtype PubMed ID
esv3635488 CNV gain 21293372
nsv1046296 CNV gain 25217958
nsv1130684 CNV deletion 24896259
nsv1423 CNV deletion 18451855
nsv470667 CNV loss 18288195
nsv565733 CNV gain 21841781
nsv565763 CNV loss 21841781

Variation tolerance for CYP46A1 Gene

Residual Variation Intolerance Score: 12.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.12; 22.65% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CYP46A1 Gene

Human Gene Mutation Database (HGMD)
CYP46A1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CYP46A1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CYP46A1 Gene

Disorders for CYP46A1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for CYP46A1 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
anus disease
  • anal disease
alpha-methylacyl-coa racemase deficiency
  • amacrd
multidrug-resistant tuberculosis
  • tuberculosis multidrug-resistant
alzheimer disease
  • ad
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for CYP46A1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CYP46A1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CYP46A1 Gene

Publications for CYP46A1 Gene

  1. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. (PMID: 10377398) Lund EG … Russell DW (Proceedings of the National Academy of Sciences of the United States of America 1999) 2 3 4 22 58
  2. Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study. (PMID: 19212968) Fu BY … Lam LC (International journal of geriatric psychiatry 2009) 3 22 44 58
  3. CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism. (PMID: 19286353) Kölsch H … Heun R (European psychiatry : the journal of the Association of European Psychiatrists 2009) 3 22 44 58
  4. Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. (PMID: 19363267) Golanska E … Corder EH (Journal of Alzheimer's disease : JAD 2009) 3 22 44 58
  5. Meta-analysis of genetic variability in the beta-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer's disease. (PMID: 17854420) Llorca J … Combarros O (Acta neurologica Scandinavica 2008) 3 22 44 58

Products for CYP46A1 Gene

Sources for CYP46A1 Gene

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