This report describes nephrotic syndrome, KANK-related. In a whole exome sequence (WES) analysis, mutations in the human kidney ankyrin repeat-containing genes KANK1, KANK2, and KANK4 were postulated to be associated with nephrotic syndrome; nephrotic syndrome associated with KANK2 has now been designated nephrotic syndrome, type 16 (MIM:617783; FBhh0000894). These genes regulate actin polymerization in multiple different cellular and developmental contexts. In Drosophila, there is a single orthologous gene, Dmel\Kank, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by a small deletion have been generated.
None of the human KANK genes has 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].
Animals homozygous for a deletion of the Dmel\Kank gene are viable and fertile. Reduction of Kank expression effected by RNAi in pericardial cells in larvae results in impaired pericardial nephrocyte function, as assayed by uptake of a protein marker into the nephrocytes. Subcellular abnormalities affecting the distribution of vesicles and lacuna channels and the number of slit diaphragms are observed.
[updated Sep. 2018 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]
KANK2 appears to function in the sequestration of steroid receptor coactivators and possibly other proteins. [Gene Cards, KANK2; 2017.11.28]
KANK1-4 have been shown to have roles in inhibition of actin nucleation, actin organisation, cell polarity, and cell growth (FBrf0226210 and references cited therein).
The KANK (KN motif and ankyrin repeat domains) family of proteins play a role in cytoskeletal formation by regulating actin polymerization. KANK1 may inhibit actin fiber formation and cell migration. [Gene Cards, KANK2; 2017.11.28]
Many to one: 4 human to 1 Drosophila; the human genes are KANK1, KANK2, KANK3, KANK4.
Many to one: 4 human to 1 Drosophila; the human genes are KANK1, KANK2, KANK3, KANK4.
Many to one: 4 human to 1 Drosophila; the human genes are KANK1, KANK2, KANK3, KANK4.
Many to one: 4 human to 1 Drosophila; the human genes are KANK1, KANK2, KANK3, KANK4.
Moderate-scoring ortholog of human genes KANK1, KANK2, KANK3, and KANK4 (1 Drosophila to 4 human); Dmel\Kank shares 23-24% identity and 33-37% similarity with the human genes.
