This report describes nephrotic syndrome 1 (NPHS1), a subtype of nephrotic syndrome; NPHS1 exhibits autosomal recessive inheritance. The human gene implicated in this disease is NPHS1, nephrin, a kidney glomerular filtration barrier protein. There are two fly orthologs, sns and hbs, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles of both genes have been generated. The fly model of NPHS1 utilizes sns, since hbs is expressed in only a subset of nephrocytes.
A UAS construct of the wild-type Hsap\NPHS1 gene has been introduced into flies. Functional complementation could not be assessed, since even moderate overexpression of Hsap\NPHS1 produces abnormal phenotypes (FBrf0207370).
Animals homozygous for most loss-of-function mutations of sns die during the embryonic stage; embryonic garland cells lack nephrocyte diaphragms and lacunae. In targeted loss of function effected by RNAi, larval garland cells are also observed to be abnormal, with reduced numbers of nephrocyte diaphragms and lacunae.
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]. It is postulated that, analogous with NPHS1 and KIRREL in the slit diaphragm in mammals, Dmel\sns and Dmel\kirre interact through their extracellular domains to form the fly nephrocyte diaphragm (see FBhh0000549). The two fly genes have been shown to interact genetically and physically.
[updated Jun. 2017 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]
[NEPHROTIC SYNDROME, TYPE 1; NPHS1](https://omim.org/entry/256300)
[NEPHRIN; NPHS1](https://omim.org/entry/602716)
Nephrotic syndrome type 1 (NPHS1) is characterized by prenatal onset of massive proteinuria followed by severe steroid-resistant nephrotic syndrome apparent at birth with rapid progression to end-stage renal failure (Kestila et al., 1998, pubmed:9660941). [From MIM:256300, 2016.06.13]
Nephrotic syndrome type 1 (NPHS1), also known as Finnish congenital nephrosis, is caused by homozygous or compound heterozygous mutation in NPHS1, the gene encoding nephrin. [From MIM:256300, 2016.06.13]
Electron microscopic studies of the kidney show effacement of the podocytes, a narrow slit, and absence of the slit diaphragm (Tryggvason et al., 2006, pubmed:16571882). Patients with congenital nephrotic syndrome exhibit an accumulation of type IV collagen in the renal cortex in renal biopsies. The accumulation of the collagen was out of proportion to another basement membrane protein, laminin. They interpreted this to mean that metabolism of type IV collagen is disturbed in this disorder (Risteli et al., 1982, pubmed:6122009). [From MIM:256300, 2016.06.15]
NPHS1 encodes a member of the immunoglobulin family of cell adhesion molecules that functions in the glomerular filtration barrier in the kidney. The gene is primarily expressed in renal tissues, and the protein is a type-1 transmembrane protein found at the slit diaphragm of glomerular podocytes. The slit diaphragm is thought to function as an ultrafilter to exclude albumin and other plasma macromolecules in the formation of urine. Mutations in this gene result in Finnish-type congenital nephrosis 1, characterized by severe proteinuria and loss of the slit diaphragm and foot processes. [provided by RefSeq, Oct 2009]
The NPHS1 gene encodes nephrin, a kidney glomerular filtration barrier protein that is an essential component of the interpodocyte-spanning slit diaphragm (Wartiovaara et al., 2004, pubmed:15545998). [From MIM:602716, 2016.06.15]
One to many: 1 human to 2 Drosophila.
Ortholog of human NPHS1 (2 Drosophila to 1 human). Dmel\sns shares 29% identity and 45% similarity with human NPHS1.
