Characterization of Dnajc12 knockout mice, a model of hypodopaminergia.

Homozygous DNAJC12 c.79-2A>G (p. V27Wfs*14) loss-of-function mutations were first reported as a cause of young-onset Parkinson's disease.

RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses.

Background: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.

A pathogenic variant in RAB32 causes autosomal dominant Parkinson's disease and activates LRRK2 kinase.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with a notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as a subset are both regulators and substrates of LRRK2 protein kinase. To explore the role of RAB GTPases in PD, we undertook a comprehensive examination of their genetic variability in familial PD.

DNAJC13 p.Asn855Ser, implicated in familial parkinsonism, alters membrane dynamics of sorting nexin 1.

DNAJC13 (RME-8) is a core co-chaperone that facilitates membrane recycling and cargo sorting of endocytosed proteins. DNAJ/Hsp40 (heat shock protein 40) proteins are highly conserved throughout evolution and mediate the folding of nascent proteins, and the unfolding, refolding or degradation of misfolded proteins while assisting in associated-membrane translocation. DNAJC13 is one of five DNAJ 'C' class chaperone variants implicated in monogenic parkinsonism.

Altered dopamine release and monoamine transporters in Vps35 p.D620N knock-in mice.

Vacuolar protein sorting 35 (VPS35) is a core component of the retromer trimer required for endosomal membrane-associated protein trafficking. The discovery of a missense mutation, p.D620N implicates retromer dysfunction in the pathogenesis of Parkinson's disease (PD).