Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression

More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing...

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Detalles Bibliográficos
Autores: Mayayo-Vallverdú, Clara|||0000-0003-0756-7790, Prat, Esther|||0000-0001-5044-4468, Vecino-Pérez, Marta, González, Laura, Gràcia-Garcia, Silvia|||0000-0002-1838-5979, San Miguel, Luz, Lopera, Noelia, Arias, Angela, Artuch, R.|||0000-0002-3422-9685, López de Heredia, Miguel|||0000-0003-2826-9565, Torrecilla, Carlos, Rousaud-Barón, Ferran, Angerri Feu, Oriol|||0000-0003-3363-6585, Errasti-Murugarren, Ekaitz|||0000-0002-6054-7900, Nunes Martínez, Virginia|||0000-0002-5747-9310
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:296609
Acceso en línea:https://ddd.uab.cat/record/296609
https://dx.doi.org/urn:doi:10.3390/ijms242417140
Access Level:acceso abierto
Palabra clave:Cystinuria
Cystine transporter
Rare disease
SLC7A13 variants
Functional analysis
Descripción
Sumario:More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded.

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