CYP46A1

Chr 14

cytochrome P450 family 46 subfamily A member 1

Also known as: CP46, CYP46

NCBI Gene: 10858 ENSG00000036530 UniProt: Q9Y6A2 OMIM: 604087

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— CYP46A1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

32 VUS of 39 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.986

Z-score 4.19

OE 0.12 (0.05–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.97Z-score

OE missense 0.52 (0.45–0.59)

156 obs / 300.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.30)

0≤0.351.4

Missense OE?0.52 (0.45–0.59)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 3 / 26.1Missense obs/exp: 156 / 300.9Syn Z: -0.73

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

VUS32

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	32	32
Likely Benign	3	3
Benign	0	0
Total	35	35

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

25 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap CYP46A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →