Cholestanol storage disease: genes and variants
Cholestanol storage disease is linked to 1 analyzed protein (CYP27A1). 28 DNA variants are known to cause it; 304 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Cholestanol storage disease
CYP27A1: Sterol 26-hydroxylase, mitochondrial
It hydroxylates sterol intermediates in bile-acid synthesis and contributes to cholesterol elimination and oxysterol production. Biallelic loss-of-function variants cause cerebrotendinous xanthomatosis, a treatable disorder with cholestanol accumulation, cataracts, tendon xanthomas, and progressive neurologic disease.
28 disease-causing and 304 uncertain variants in CYP27A1 are linked to Cholestanol storage disease.
Where Cholestanol storage disease variants cluster
- CYP27A1 Sterol-binding (positions 384–398): 3 of 28 disease-causing changes, 3.8× more than its size predicts.
Known disease-causing variants in Cholestanol storage disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CYP27A1 R395S | 395 | Sterol-binding | Disease-causing (★★) |
| CYP27A1 R395H | 395 | Sterol-binding | Disease-causing (★★) |
| CYP27A1 R395C | 395 | Sterol-binding | Disease-causing (★★) |
| CYP27A1 R474Q | 474 | Disease-causing (★★) | |
| CYP27A1 R474W | 474 | Disease-causing (★★) | |
| CYP27A1 R127Q | 127 | Disease-causing (★★) | |
| CYP27A1 R127G | 127 | Disease-causing (★★) | |
| CYP27A1 A335V | 335 | Disease-causing (★★) | |
| CYP27A1 R479C | 479 | Disease-causing (★★) | |
| CYP27A1 T339M | 339 | Disease-causing (★★) | |
| CYP27A1 R405Q | 405 | Disease-causing (★★) | |
| CYP27A1 R405W | 405 | Disease-causing (★★) | |
| CYP27A1 M130K | 130 | Disease-causing (★★) | |
| CYP27A1 R137Q | 137 | Disease-causing (★★) | |
| CYP27A1 W268C | 268 | Disease-causing (★★) | |
| CYP27A1 A216P | 216 | Disease-causing (★★) | |
| CYP27A1 K259R | 259 | Disease-causing (★★) | |
| CYP27A1 R513C | 513 | Disease-causing (★★) | |
| CYP27A1 R474P | 474 | Disease-causing (★) | |
| CYP27A1 R479P | 479 | Disease-causing (★) | |
| CYP27A1 R479S | 479 | Disease-causing (★) | |
| CYP27A1 R479L | 479 | Disease-causing (★) | |
| CYP27A1 R137P | 137 | Disease-causing (★) | |
| CYP27A1 M1V | 1 | Disease-causing (★) | |
| CYP27A1 G145E | 145 | Disease-causing | |
| CYP27A1 P468S | 468 | Disease-causing | |
| CYP27A1 P401R | 401 | Disease-causing | |
| CYP27A1 D354G | 354 | Disease-causing |
Uncertain variants in Cholestanol storage disease that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| CYP27A1 R137W | 137 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R137Q at the same position is pathogenic; REVEL 0.821 | |
| CYP27A1 M130T | 130 | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; M130K at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.735 |
Frequently asked questions
Which genes are linked to Cholestanol storage disease?
In CATVariant, Cholestanol storage disease is linked to 1 analyzed protein: CYP27A1 (Sterol 26-hydroxylase, mitochondrial).
How many genetic variants are linked to Cholestanol storage disease?
337 variants: 28 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 304 are of uncertain significance or have conflicting reports.
Which uncertain variants in Cholestanol storage disease look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example CYP27A1 R137W and CYP27A1 M130T. These are leads for expert review, not diagnoses.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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