CYP27A1

Chr 2AR

cytochrome P450 family 27 subfamily A member 1

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.381 OMIM phenotype
Clinical SummaryCYP27A1
🧬
Gene-Disease Validity (ClinGen)
cerebrotendinous xanthomatosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.38LOEUF
pLI 0.000
Z-score -0.02
OE 1.00 (0.741.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.31Z-score
OE missense 1.05 (0.961.15)
319 obs / 303.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.00 (0.741.38)
00.351.4
Missense OE1.05 (0.961.15)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 28 / 27.9Missense obs/exp: 319 / 303.8Syn Z: 0.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCYP27A1-related cerebrotendinous xanthomatosisLOFAR

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

DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CYP27A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗