This report describes a model of nephrotic syndrome, type 9 (NPHS9), a subtype of nephrotic syndrome; NPHS9 exhibits autosomal recessive inheritance. The human gene implicated in this disease is COQ8B (Coenzyme Q8B), which encodes an enzyme thought to be involved in the biosynthesis of CoQ10 (ubiquinone). There is a single orthologous gene in Drosophila, Coq8, for which missense mutations and RNAi-targeting constructs have been generated. Coq8 is also orthologous to a second gene in human, COQ8A, which is implicated in a subtype of primary coenzyme Q10 deficiency (OMIM:612016).
The human COQ8B 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].
Very little is known about the Drosophila Coq8 gene. RNA-effected knockdown of Coq8 in pericardial nephrocytes (analogous to glomerular podocytes in the mammalian kidney) results in reduced uptake of a a protein marker into the nephrocyte (using tagged atrial natriuretic peptide, ANP).
[updated Sep. 2017 by FlyBase; FBrf022219
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 OMIM:256300, 2016.06.13]
[NEPHROTIC SYNDROME, TYPE 9; NPHS9](https://omim.org/entry/615573)
[COENZYME Q8B; COQ8B](https://omim.org/entry/615567)
Nephrotic syndrome type 9 (NPHS9) is an autosomal recessive chronic kidney disorder characterized by significant proteinuria resulting in hypoalbuminemia and edema. Onset is in the first or second decade of life. The disorder is steroid treatment-resistant and usually progresses to end-stage renal disease requiring transplantation. Renal biopsy shows focal segmental glomerulosclerosis (FSGS) or collapsing FSGS (summary by Ashraf et al., 2013; pubmed:24270420; FBrf0236627). [from OMIM:615573; 2017.09.18]
COQ8B (coenzyme Q8B) appears to have a role in CoQ10 (ubiquinone) biosynthesis. CoQ10 is a lipid-soluble component of virtually all cell membranes and has a critical role in transporting electrons along the respiratory chain of the mitochondrial inner membrane. [from OMIM:615567; 2017.09.18]
COQ8B (Coenzyme Q8B) encodes an atypical kinase involved in the biosynthesis of coenzyme Q. The COQ8B protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. [Gene Cards, COQ8B; 2017.09.18]