Dyslipidemia: genes and variants

Genes linked to Dyslipidemia

• LDLR: Low-density lipoprotein receptor

  It removes ApoB-containing LDL particles from the circulation through receptor-mediated endocytosis, especially in hepatocytes. Loss-of-function variants are the most common cause of familial hypercholesterolemia and lead to lifelong LDL elevation and premature atherosclerotic disease.

  32 disease-causing and 17 uncertain variants in LDLR are linked to Dyslipidemia.

Where Dyslipidemia variants cluster

• LDLR EGF-like 2 (positions 354–393): 5 of 32 disease-causing changes, 3.4× more than its size predicts.
• LDLR LDL-receptor class A 4 (positions 146–186): 4 of 32 disease-causing changes, 2.6× more than its size predicts.
• LDLR LDL-receptor class A 3 (positions 107–145): 3 of 32 disease-causing changes, 2.1× more than its size predicts.

Known disease-causing variants in Dyslipidemia

Which prediction tools work for Dyslipidemia

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• AlphaMissense: 100 out of 100
• EVE: 100 out of 100
• MetaLR: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 97 out of 100
• MutPred2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 96 out of 100
• PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 78 out of 100

Same protein, different disease

• Hypercholesterolemia, familial, 1 is also caused by LDLR variants; they fall mostly in different places as the Dyslipidemia variants (558 disease-causing).
• Familial hypercholesterolemia is also caused by LDLR variants; they fall mostly in different places as the Dyslipidemia variants (296 disease-causing).
• Homozygous familial hypercholesterolemia is also caused by LDLR variants; they fall partly in the same places as the Dyslipidemia variants (26 disease-causing).

Diseases related to Dyslipidemia

• Hypercholesterolemia, familial, 1, also linked to LDLR
• Familial hypercholesterolemia, also linked to LDLR
• Homozygous familial hypercholesterolemia, also linked to LDLR
• Myocardial infarction, also linked to LDLR

Frequently asked questions

Which genes are linked to Dyslipidemia?

In CATVariant, Dyslipidemia is linked to 1 analyzed protein: LDLR (Low-density lipoprotein receptor).

How many genetic variants are linked to Dyslipidemia?

49 variants: 32 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.

Which uncertain variants in Dyslipidemia 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 Dyslipidemia?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 19 disease-causing and 17 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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