ADCK4 “reenergizes” nephrotic syndrome
Laura Malaga-Dieguez, Katalin Susztak
Laura Malaga-Dieguez, Katalin Susztak
Published November 25, 2013
Citation Information: J Clin Invest. 2013;123(12):4996-4999. https://doi.org/10.1172/JCI73168.
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Commentary

ADCK4 “reenergizes” nephrotic syndrome

Abstract

Steroid-resistant nephrotic syndrome has a poor prognosis and often leads to end-stage renal disease development. In this issue of the JCI, Ashraf and colleagues used exome sequencing to identify mutations in the aarF domain containing kinase 4 (ADCK4) gene that cause steroid-resistant nephrotic syndrome. Patients with ADCK4 mutations had lower coenzyme Q10 levels, and coenzyme Q10 supplementation ameliorated renal disease in a patient with this particular mutation, suggesting a potential therapy for patients with steroid-resistant nephrotic syndrome with ADCK4 mutations.

Authors

Laura Malaga-Dieguez, Katalin Susztak

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Figure 1

The products of the genes whose mutations have been found to cause SRNS reside in the podocyte.

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The products of the genes whose mutations have been found to cause SRNS ...
Mutations of these genes lead to abnormal or absent protein products. The complex ultrastructural nature of the podocyte makes it difficult to judge the exact function of each of these proteins on a molecular level and thus classify the different mutations. Slit diaphragm–associated (SD-associated) mutations (purple) include nephrin (NPHS1), podocin (NPHS2), PLCε1 (PLCE1), CD2-associated protein (CD2AP), transient receptor potential channel 6 (TRPC6), and protein tyrosine phosphatase receptor type O (PTPRO), and ADCK4 (orange). Cytoskeleton and foot process actin network–associated mutations (red) include α-actinin-4 (ACTN4), inverted formin 2 (INF2), myosin 1E (MYO1E), Rho-GDP-dissociation inhibitor 1 (ARHGDIA), and Rho-GTPase–activating protein 24 (ARHGAP24). Nuclear- or trascription-associated mutations (gray) include Wilm’s tumor protein (WT1), LIM/homeobox transcription factor 1β (LMX1B), ATP-driven annealing helicase (SMARCAL1), and nuclear RNA export factor 5 (NXF5). Glomerular basement membrane–associated (GMB-associated) mutations (pink) include laminin-β2 (LAMB2), integrin-β4 (ITGB4), and integrin-α3 (ITGA3). Mitochondia-associated mutations (brown) include parahydroxybenzoate-polyprenyl transferase (COQ2), ubiquinone biosynthesis monooxygenase (COQ6), decaprenyl-diphosphate synthase subunit 2 (PDSS2), mitochondrially encoded tRNA leucine 1 (MTTL1), and ADCK4. Lysosome-associated mutations (maroon) include scavenger receptor class B, member 2 (SCARB2).