Sitosterolemia: genes and variants
Sitosterolemia is linked to 2 analyzed proteins (ABCG5 and ABCG8). 8 DNA variants are known to cause it; 304 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: sitosterolemia 1; sitosterolemia 2
Genes linked to Sitosterolemia
ABCG5: ATP-binding cassette sub-family G member 5
Together with ABCG8, it limits sterol accumulation by promoting cholesterol and plant-sterol excretion into bile and back into the intestinal lumen. Biallelic loss-of-function variants cause sitosterolemia, with elevated plant sterols, premature atherosclerosis, and sometimes hematologic abnormalities.
5 disease-causing and 188 uncertain variants in ABCG5 are linked to Sitosterolemia.
ABCG8: ATP-binding cassette sub-family G member 8
Together with ABCG5, it drives sterol efflux from hepatocytes and enterocytes, limiting absorption and promoting biliary elimination of cholesterol and plant sterols. Biallelic loss-of-function variants cause sitosterolemia and can lead to premature atherosclerotic cardiovascular disease.
3 disease-causing and 116 uncertain variants in ABCG8 are linked to Sitosterolemia.
Where Sitosterolemia variants cluster
- ABCG5 ABC transmembrane type-2 (positions 388–645): 4 of 5 disease-causing changes, 2.0× more than its size predicts.
Known disease-causing variants in Sitosterolemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCG5 R419H | 419 | ABC transmembrane type-2 | Disease-causing (★★) |
| ABCG5 R389H | 389 | ABC transmembrane type-2 | Disease-causing (★★) |
| ABCG8 G574R | 574 | ABC transmembrane type-2 | Disease-causing (★★) |
| ABCG5 S44A | 44 | Cytoplasmic | Disease-causing (★) |
| ABCG5 N437K | 437 | ABC transmembrane type-2 | Disease-causing (★) |
| ABCG5 R419P | 419 | ABC transmembrane type-2 | Disease-causing |
| ABCG8 P231T | 231 | ABC transporter | Disease-causing |
| ABCG8 L596R | 596 | ABC transmembrane type-2 | Disease-causing |
Which prediction tools work for Sitosterolemia
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 96 out of 100
- SIFT: 95 out of 100
- phyloP: 86 out of 100
Frequently asked questions
Which genes are linked to Sitosterolemia?
In CATVariant, Sitosterolemia is linked to 2 analyzed proteins: ABCG5 (ATP-binding cassette sub-family G member 5) and ABCG8 (ATP-binding cassette sub-family G member 8).
How many genetic variants are linked to Sitosterolemia?
368 variants: 8 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 Sitosterolemia look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Sitosterolemia?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 8 disease-causing and 35 harmless variants).
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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