Next Article in Journal
Active Protein Network Analysis Reveals Coordinated Modules and Critical Proteins Involving Extracellular Electron Transfer Process
Previous Article in Journal
Investigating the Role of B9D1 in Meckel–Gruber Syndrome: A Case Report and Comprehensive Literature Review
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Genes
Volume 16
Issue 6
10.3390/genes16060642
genes-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Collagen Type IV Variants and Kidney Cysts: Decoding the COL4A Puzzle

by
Matteo Rigato
1,2,
Carlotta Caprara
1,2,3,
J. Said Cabrera-Aguilar
2,4,
Nenzi Marzano
2,
Anna Giuliani
1,2,
Barbara Mancini
3,
Fiorella Gastaldon
1,2,
Claudio Ronco
2,
Monica Zanella
1,2,
Daniela Zuccarello
3,* and
Valentina Corradi
1,2
1
Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy
2
The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy
3
Department of Medical Genetics and Genomics, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy
4
Nephrology Service, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara 44200, Mexico
*
Author to whom correspondence should be addressed.
Genes 2025, 16(6), 642; https://doi.org/10.3390/genes16060642
Submission received: 29 April 2025 / Revised: 20 May 2025 / Accepted: 25 May 2025 / Published: 27 May 2025
(This article belongs to the Section Molecular Genetics and Genomics)
Versions Notes

Abstract

Pathogenic variants in type IV collagen genes (COL4A3, COL4A4, COL4A5) are classically associated with Alport syndrome (AS), a hereditary nephropathy primarily affecting the glomerular basement membrane (GBM). Recent findings, however, suggest a broader phenotypic spectrum that includes renal cyst formation, raising questions about overlapping mechanisms with other cystic kidney diseases. Clinically, renal cysts have been increasingly reported in patients with autosomal dominant and X-linked forms of Alport syndrome, particularly in association with glycine missense variants. The most recent studies focusing on the cystic phenotype in Alport syndrome provide growing support for the idea that variants in type IV collagen genes are associated with an increased likelihood of developing renal cysts, likely through mechanisms involving the structural integrity of renal basement membranes. In this review, we explore evidence from murine models and human studies indicating defects in collagen IV and discuss their contribution to cystogenesis. These observations underscore the need for broader genetic screening strategies and further investigation into the molecular mechanisms underlying this emerging phenotype.
Keywords: cystic kidney disease; COL4A; collagen variants; kidney cysts; Alport syndrome; ADPKD cystic kidney disease; COL4A; collagen variants; kidney cysts; Alport syndrome; ADPKD

Share and Cite

MDPI and ACS Style

Rigato, M.; Caprara, C.; Cabrera-Aguilar, J.S.; Marzano, N.; Giuliani, A.; Mancini, B.; Gastaldon, F.; Ronco, C.; Zanella, M.; Zuccarello, D.; et al. Collagen Type IV Variants and Kidney Cysts: Decoding the COL4A Puzzle. Genes 2025, 16, 642. https://doi.org/10.3390/genes16060642

AMA Style

Rigato M, Caprara C, Cabrera-Aguilar JS, Marzano N, Giuliani A, Mancini B, Gastaldon F, Ronco C, Zanella M, Zuccarello D, et al. Collagen Type IV Variants and Kidney Cysts: Decoding the COL4A Puzzle. Genes. 2025; 16(6):642. https://doi.org/10.3390/genes16060642

Chicago/Turabian Style

Rigato, Matteo, Carlotta Caprara, J. Said Cabrera-Aguilar, Nenzi Marzano, Anna Giuliani, Barbara Mancini, Fiorella Gastaldon, Claudio Ronco, Monica Zanella, Daniela Zuccarello, and et al. 2025. "Collagen Type IV Variants and Kidney Cysts: Decoding the COL4A Puzzle" Genes 16, no. 6: 642. https://doi.org/10.3390/genes16060642

APA Style

Rigato, M., Caprara, C., Cabrera-Aguilar, J. S., Marzano, N., Giuliani, A., Mancini, B., Gastaldon, F., Ronco, C., Zanella, M., Zuccarello, D., & Corradi, V. (2025). Collagen Type IV Variants and Kidney Cysts: Decoding the COL4A Puzzle. Genes, 16(6), 642. https://doi.org/10.3390/genes16060642

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop