Umod, encoding uromodulin (also known as Tamm-Horsfall protein), is a kidney-specific gene. Uromodulin is the most abundant protein excreted in normal urine and has important functions in the kidney and urine [4,5]. The gene is associated with pathways related to kidney function maintenance. Genetic models are valuable for studying its functions as genetic factors associated with Umod have implications for understanding kidney disease mechanisms [1,4].

Mutations in Umod are a major cause of autosomal dominant tubulointerstitial kidney disease (ADTKD), which leads to chronic kidney disease (CKD) and end-stage renal disease (ESRD). ADTKD-Umod is more frequently diagnosed than ADTKD-MUC1, and patients with ADTKD-Umod have distinct clinical features such as shorter median gout-free survival and reduced urinary uromodulin levels compared to ADTKD-MUC1 patients [2]. There are also intermediate-effect Umod variants that confer risk for CKD, with carriers showing reduced disease severity and intermediate reduction of urinary uromodulin levels [5]. In a Chinese pediatric case, a novel Umod gene mutation was found in an ADTKD family, extending the understanding of Umod gene mutation spectrum and phenotype in children [3]. In Taiwanese CKD families, new Umod missense variants were identified, and in vitro studies showed defects in cell membrane trafficking of the related uromodulin variants [6].

In conclusion, Umod is crucial for normal kidney function, and its mutations are significantly associated with kidney diseases, especially ADTKD and CKD. The study of Umod through genetic models, as evidenced by various patient-based findings, helps in understanding the pathogenesis and prognosis of these kidney diseases, potentially providing insights for therapeutic development.

References:

1. Devuyst, Olivier, Bochud, Murielle, Olinger, Eric. 2022. UMOD and the architecture of kidney disease. In Pflugers Archiv : European journal of physiology, 474, 771-781. doi:10.1007/s00424-022-02733-4. https://pubmed.ncbi.nlm.nih.gov/35881244/

2. Olinger, Eric, Hofmann, Patrick, Kidd, Kendrah, Bleyer, Anthony J, Devuyst, Olivier. 2020. Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1. In Kidney international, 98, 717-731. doi:10.1016/j.kint.2020.04.038. https://pubmed.ncbi.nlm.nih.gov/32450155/

3. Yang, Jing, Zhang, Yu, Zhou, Jianhua. 2019. UMOD gene mutations in Chinese patients with autosomal dominant tubulointerstitial kidney disease: a pediatric case report and literature review. In BMC pediatrics, 19, 145. doi:10.1186/s12887-019-1522-7. https://pubmed.ncbi.nlm.nih.gov/31068150/

4. Devuyst, Olivier, Pattaro, Cristian. 2017. The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease. In Journal of the American Society of Nephrology : JASN, 29, 713-726. doi:10.1681/ASN.2017070716. https://pubmed.ncbi.nlm.nih.gov/29180396/

5. Olinger, Eric, Schaeffer, Céline, Kidd, Kendrah, Rampoldi, Luca, Devuyst, Olivier. 2022. An intermediate-effect size variant in UMOD confers risk for chronic kidney disease. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2114734119. doi:10.1073/pnas.2114734119. https://pubmed.ncbi.nlm.nih.gov/35947615/

6. Chen, Huan-Da, Yu, Chih-Chuan, Yang, I-Hsiao, Chang, Jer-Ming, Hwang, Daw-Yang. 2022. UMOD Mutations in Chronic Kidney Disease in Taiwan. In Biomedicines, 10, . doi:10.3390/biomedicines10092265. https://pubmed.ncbi.nlm.nih.gov/36140366/