Parkinson disease, late-onset: genes and variants

Genes linked to Parkinson disease, late-onset

• GBA1: Lysosomal acid glucosylceramidase

  It degrades glucosylceramide within lysosomes and is essential for normal sphingolipid turnover. Biallelic pathogenic variants cause Gaucher disease, while heterozygous pathogenic variants are among the strongest genetic risk factors for Parkinson disease.

  8 disease-causing and 10 uncertain variants in GBA1 are linked to Parkinson disease, late-onset.

• MAPT: Microtubule-associated protein tau

  Its tau isoforms stabilize and organize neuronal microtubules, especially in axons, while also participating in transport and signaling. Pathogenic variants cause inherited frontotemporal dementia, and abnormal tau aggregation defines multiple neurodegenerative tauopathies.

  0 disease-causing and 7 uncertain variants in MAPT are linked to Parkinson disease, late-onset.

Weakly linked (only a few uncertain records): PINK1, PARK7 and VPS35.

Known disease-causing variants in Parkinson disease, late-onset

Which prediction tools work for Parkinson disease, late-onset

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

• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 79 out of 100
• PolyPhen-2: 78 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Gaucher disease is also caused by GBA1 variants; they fall mostly in different places as the Parkinson disease, late-onset variants (132 disease-causing).
• Lewy body dementia is also caused by GBA1 variants; they fall mostly in different places as the Parkinson disease, late-onset variants (6 disease-causing).
• Gaucher disease perinatal lethal is also caused by GBA1 variants; they fall mostly in different places as the Parkinson disease, late-onset variants (5 disease-causing).
• Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome is also caused by GBA1 variants; they fall mostly in different places as the Parkinson disease, late-onset variants (3 disease-causing).

Diseases related to Parkinson disease, late-onset

• Parkinson disease, also linked to GBA1 and MAPT
• Gaucher disease, also linked to GBA1
• Alzheimer disease, also linked to MAPT
• Frontotemporal dementia, also linked to MAPT
• Pick disease, also linked to MAPT
• Lewy body dementia, also linked to GBA1
• Supranuclear palsy, progressive, 1, also linked to MAPT
• Gaucher disease perinatal lethal, also linked to GBA1
• Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome, also linked to GBA1

Frequently asked questions

Which genes are linked to Parkinson disease, late-onset?

In CATVariant, Parkinson disease, late-onset is linked to 2 analyzed proteins: GBA1 (Lysosomal acid glucosylceramidase) and MAPT (Microtubule-associated protein tau).

How many genetic variants are linked to Parkinson disease, late-onset?

31 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 21 are of uncertain significance or have conflicting reports.

Which uncertain variants in Parkinson disease, late-onset 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 Parkinson disease, late-onset?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.79, based on 8 disease-causing and 48 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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