Child Kidney Dis.  2023 Jun;27(1):19-25. 10.3339/ckd.23.003.

CUBN mutation: a benign genetic cause of proteinuria?

• Lee HK

• KMID: 2544233
• DOI: http://doi.org/10.3339/ckd.23.003

Abstract

Proteinuria is an important risk factor for renal and cardiovascular disease. It is associated with a risk for glomerulonephritis, chronic kidney disease, and end-stage renal disease. Therefore, if persistent proteinuria is detected, kidney biopsy is considered to diagnose and treat the underlying disease. Recently, variants in the cubilin gene (CUBN), which is associated with albuminuria, have been reported. This gene encodes cubilin, a membrane glycoprotein receptor expressed in the renal proximal tubules. Cubilin is a component of the megalin and cubilin-amnionless complex that mediates albumin reabsorption into the proximal tubules through endocytosis. A defect in cubilin leads to a reduction in albumin reuptake, resulting in albumin-dominant proteinuria. Although numerous controversies exist, several reports suggest that cubilin defects lead to proteinuria with a high portion of albuminuria but may not impair renal filtration function. If albuminuria due to reduced cubilin function is confirmed as a benign condition, we can consider using genetic studies to detect CUBN mutations in patients with proteinuria and they may not require any treatment or kidney biopsy. Here, we review recent papers on CUBN mutations and discuss the prognosis and management of individuals with this mutation.

Keyword

Cubulin; Proteinuria

Figure

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  Fig. 1. Endo-lysosomal system in proximal tubular epithelial cells and the related genetic disorders. EE, early endosome. Adapted from Willnow, Kidney Int 2017;91:776-8 [6].

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  Fig. 2. Endocytic megalin and cubilin-amnionless complex in the apical membrane of the renal proximal tubule. EGF, epidermal growth factor; CUB, complement sub-components C1r/C1s, Uegf, and Bmp1. Adapted from Gburek et al. Int J Mol Sci 2021;22:5809 [1].

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  Fig. 3. Schematic representation of cubilin and amnionless. IGS, Imerslund-Gräsbeck syndrome; EGF, epidermal growth factor; CUB, complement sub-components C1r/C1s, Uegf, and Bmp1; IF-B12, intrinsic factor-vitamin B12. Adapted from Storm et al. BMC Med Genet 2013;14:111 [10].

Reference

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