Several genetic variants of HSPA9 have been identified in Parkinson disease patients, but their relevance to development of that disease has not been established. HSPA9 encodes a member of the heat shock protein 70 gene family and acts as a chaperone protein. There is a single high-scoring orthologous gene in Drosophila, Hsc70-5, for which multiple genetic reagents are available including RNAi-targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis.
Multiple UAS constructs of the human Hsap\HSPA9 gene have been introduced into flies, including wild-type and variants implicated in Parkinson disease; see the 'Disease-Implicated Variants' table, below. Heterologous rescue (functional complementation) of the peroxisome-loss phenotype observed for knockdown of Hsc70-5 has been reported for the wild-type Hsap\HSPA9 construct; the disease-associated variants fail to rescue.
Homozygous null alleles of Hsc70-5 are lethal. Knockdown of Hsc70-5 in muscle or fat tissue results in loss of peroxisomes. Pan-neuronal reduction of Hsc70-5 expression recapitulates some of the defects observed in Drosophila models of Parkinson disease including shortened life span and and progressive locomotor defects.
[updated Oct. 2021 by FlyBase; FBrf0222196]
HSPA9 encodes a member of the heat shock protein 70 gene family and acts as a chaperone protein. The HSPA9 protein is primarily localized to the mitochondria but is also found in the endoplasmic reticulum, plasma membrane and cytoplasmic vesicles. HSPA9 plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. [Gene Cards, HSPA9; 2021.10.26]
One to one: 1 human gene to 1 Drosophila gene; additional related genes is both species.
High-scoring ortholog of human HSPA9 (1 Drosophila to 1 human); additional related genes is both species. Dmel\Hsc70-5 shares 77% identity and 88% similarity with the human gene.
