The human gene GAPVD1 has been implicated in the development of nephrotic syndrome based on exome-sequencing analysis of two families affected by the disease; like most subtypes of nephrotic syndrome, this forms exhibits autosomal recessive inheritance. GAPVD1 encodes a protein that acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF); it is involved in regulation of vesicle-mediated transport associated with a number of specific pathways. There is a single orthologous gene in Drosophila, Dmel\Gapvd1, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human GAPVD1 gene has not been introduced into flies.
In the fly, nephrocytes act in a manner analogous to human podocytes: the fly nephrocyte diaphragm functions like the mammalian slit diaphragm to regulate filtration; the nephrocytes may also function in protein reabsorption [reviewed in FBrf0220711 and FBrf0235870; see also the human disease model report 'kidney disease (fly models overview)' FBhh0000738].
Knockdown of Dmel\Gapvd1 in nephrocytes, effected by RNAi, impairs the filtration function of the nephrocytes, as assayed by tracer uptake. Ectopic nephrocyte diaphragms are observed, associated with Drosophila proteins normally present on these structures, sns and kirre (Dmel\sns is one of two Drosophila orthologs of human nephrin, see FBhh0000318; Dmel\kirre is orthologous to human KIRREL genes; see FBhh0000549).
[updated Jan. 2019 by FlyBase; FBrf0222196]
The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996, pubmed:8606597). [From MIM:256300, 2016.06.13]
The GAPVD1 protein acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization, and EGFR trafficking and degradation. It has GEF activity for RAB5A and GAP activity for RAS genes.
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human GAPVD1 (1 Drosophila to 1 human). Dmel\Gapvd1 shares 26% identity and 42% similarity with the human gene.
