CYP27A1

Chr 2AR

cytochrome P450 family 27 subfamily A member 1

Also known as: CP27, CTX, CYP27

NCBI Gene: 1593 ENSG00000135929 UniProt: Q02318 OMIM: 606530

The encoded cytochrome P450 enzyme catalyzes the hydroxylation of cholesterol and its derivatives to convert excess cholesterol to bile acids, serving as the major pathway for cholesterol elimination from the body. Mutations cause cerebrotendinous xanthomatosis, an autosomal recessive lipid storage disease characterized by abnormal cholesterol and cholestanol accumulation in tissues including the brain. The pathogenic mechanism involves gain-of-function effects that disrupt normal cholesterol homeostasis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 mitochondrial protein oxidizes cholesterol intermediates as part of the bile synthesis pathway. Since the conversion of cholesterol to bile acids is the major route for removing cholesterol from the body, this protein is important for overall cholesterol homeostasis. Mutations in this gene cause cerebrotendinous xanthomatosis, a rare autosomal recessive lipid storage disease. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.381 OMIM phenotype

Clinical Summary— CYP27A1

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Gene-Disease Validity (ClinGen)

cerebrotendinous xanthomatosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

224 unique Pathogenic / Likely Pathogenic· 428 VUS of 1257 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CYP27A1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.38LOEUF

pLI 0.000

Z-score -0.02

OE 1.00 (0.74–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.05 (0.96–1.15)

319 obs / 303.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.00 (0.74–1.38)

0≤0.351.4

Missense OE?1.05 (0.96–1.15)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 28 / 27.9Missense obs/exp: 319 / 303.8Syn Z: 0.29

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCYP27A1-related cerebrotendinous xanthomatosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6549th %ile

GOF

0.6540th %ile

LOF

0.3551th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1257 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic102

Likely Pathogenic122

VUS428

Likely Benign492

Benign20

Conflicting85

102

Pathogenic

122

Likely Pathogenic

428

VUS

492

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	84	9	8	1	102
Likely Pathogenic	97	22	2	1	122
VUS	9	385	27	7	428
Likely Benign	0	8	167	317	492
Benign	0	1	17	2	20
Conflicting	—				85
Total	190	425	221	328	1,249

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap CYP27A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →