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General Information
Name
nephrotic syndrome, type 9
FlyBase ID
FBhh0000621
Disease Ontology Term
Parent Disease
Overview

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

Disease Summary Information
Parent Disease Summary: nephrotic syndrome
Symptoms and phenotype

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]

Specific Disease Summary: nephrotic syndrome, type 9
OMIM report

[NEPHROTIC SYNDROME, TYPE 9; NPHS9](https://omim.org/entry/615573)

Human gene(s) implicated

[COENZYME Q8B; COQ8B](https://omim.org/entry/615567)

Symptoms and phenotype

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]

Genetics

Nephrotic syndrome type 9 (NPHS9) is caused by homozygous or compound heterozygous mutation in the COQ8B gene (ADCK4). [from OMIM:615573; 2017.09.18]

Cellular phenotype and pathology
Molecular information

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]

External links
Disease synonyms
nephrotic syndrome 9
NPHS9
steroid-resistant nephrotic syndrome
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; the second human gene is COQ8A.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human COQ8B and COQ8A (1 Drosophila to 2 human). Dmel\CG32649 shares 51-52% identity and 68-69% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      Models Based on Experimental Evidence ( 4 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      References (6)