Adult onset neurodegenerative disorder

Gene: RAB32

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 4:58 p.m. | Last Modified: 24 Feb 2025, 4:58 p.m.

Panel Version: 7.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: Although all reported cases were identified with the same p.Ser71Arg variant, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 8 Nov 2024, 6:37 p.m. | Last Modified: 8 Nov 2024, 6:37 p.m.

Panel Version: 7.5

Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #620923).

Created: 8 Nov 2024, 6:35 p.m. | Last Modified: 8 Nov 2024, 6:35 p.m.

Panel Version: 7.4

PMID:38614108 reported seven patients from three families and 13 unrelated individuals with Parkinson disease. The mean age was 54.6 years with ages ranging from 31 to 81 years. They were all identified with the same p.Ser71Arg variant in RAB32 gene.

PMID:38858457 reported 18 unrelated patients with Parkinson disease, carrying the same p.Ser71Arg variant. The mean age of onset was 56 years with ages ranging from 39 to 82 years. This variant was confirmed in all cases via Sanger sequencing and segregated with PD in three families. There is also functional data available.

Created: 8 Nov 2024, 6:34 p.m. | Last Modified: 8 Nov 2024, 6:34 p.m.

Panel Version: 7.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Parkinson disease 26, autosomal dominant, susceptibility to}, OMIM:620923

Publications

• 38614108
• 38858457

Green List (high evidence)

The PMID: 38858457 paper describes: "Exome-wide analyses converged on RAB32 as a novel PD gene identifying c.213C > G/p.S71R as a high-risk variant presenting in ~0.7% of familial PD cases while observed in only 0.004% of controls (odds ratio of 65.5). This variant was confirmed in all cases via Sanger sequencing and segregated with PD in three families." + functional data. Enough evidence for the green rating.
Sources: Literature

Created: 26 Jun 2024, 7:57 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Parkinson’s disease

Publications

• PMID: 38858457

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments