CYP46A1

cytochrome P450 family 46 subfamily A member 1, the group of Cytochrome P450 family 46

Basic information

Region (hg38): 14:99684297-99727301

Previous symbols: [ "CYP46" ]

Links

ENSG00000036530 ∙ NCBI:10858 ∙ OMIM:604087 ∙ HGNC:2641 ∙ Uniprot:Q9Y6A2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP46A1 gene.

• Inborn genetic diseases (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP46A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			4	1		5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	1	0

Variants in CYP46A1

This is a list of pathogenic ClinVar variants found in the CYP46A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-99691808-G-T		not specified	Uncertain significance (Oct 04, 2022)
14-99699891-G-A		Pulmonary disease, chronic obstructive, susceptibility to	protective (May 11, 2022)
14-99700081-A-G		not specified	Likely benign (Feb 05, 2024)
14-99715927-G-A		not specified	Uncertain significance (Nov 06, 2023)
14-99718105-G-A		not specified	Uncertain significance (Feb 27, 2024)
14-99726558-T-C		not specified	Uncertain significance (Jun 06, 2023)
14-99726605-C-T		not specified	Uncertain significance (Feb 09, 2023)
14-99726623-C-T		not specified	Uncertain significance (Sep 22, 2023)
14-99726692-G-A		not specified	Uncertain significance (Jan 22, 2024)
14-99726704-G-A		not specified	Likely benign (Aug 12, 2021)
14-99726707-C-A		not specified	Uncertain significance (Oct 06, 2021)
14-99726711-C-T		not specified	Uncertain significance (Oct 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP46A1	protein_coding	protein_coding	ENST00000261835	15	42998

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.986	0.0145	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.97	156	301	0.519	0.0000189	3233
Missense in Polyphen		29	106.89	0.2713		1094
Synonymous	-0.733	134	124	1.08	0.00000791	1015
Loss of Function	4.19	3	26.1	0.115	0.00000111	313

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:18621681, ECO:0000269|PubMed:20667828}.
• Pathway: Primary bile acid biosynthesis - Homo sapiens (human);27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids (Consensus)

Recessive Scores

• pRec: 0.351

Intolerance Scores

• loftool: 0.259
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.157
• hipred: Y
• hipred_score: 0.745
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cyp46a1
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: bile acid biosynthetic process;cholesterol catabolic process;xenobiotic metabolic process;nervous system development;sterol metabolic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;organelle membrane
• Molecular function: iron ion binding;steroid hydroxylase activity;heme binding;cholesterol 24-hydroxylase activity