Normal Function
The UMOD gene provides instructions for making a protein called uromodulin. This protein is only produced in a part of the kidney called the loop of Henle. This area of the kidney works to prevent the loss of important nutrients and minerals in urine by pulling these molecules back into the body.
Uromodulin is thought to play a role in the transport of sodium and potassium within the loop of Henle; the body uses these minerals to help control the amount of water in urine. Uromodulin also maintains and protects the lining of the loop of Henle and may play a role in protecting the body against urinary tract infections and kidney stones.
Health Conditions Related to Genetic Changes
Autosomal dominant tubulointerstitial kidney disease-UMOD
More than 50 different variants (also called mutations) in the UMOD gene have been found to cause autosomal dominant tubulointerstitial kidney disease-UMOD (ADTKD-UMOD), an inherited condition that causes progressive kidney disease. Most of these variants change single protein building blocks (amino acids) in the uromodulin protein.
The gene variants that cause ADTKD-UMOD change the structure of uromodulin, which prevents the protein from traveling to where it is needed in the loop of Henle. A lack of functioning uromodulin interferes with the loop of Henle's ability to transport sodium and potassium. In addition, the buildup of uromodulin may trigger the self-destruction (apoptosis) of cells in the kidney, leading to kidney disease and eventual kidney failure.
More About This Health ConditionOther Names for This Gene
- Tamm-Horsfall glycoprotein
- THGP
- THP
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bernascone I, Vavassori S, Di Pentima A, Santambrogio S, Lamorte G, Amoroso A, Scolari F, Ghiggeri GM, Casari G, Polishchuk R, Rampoldi L. Defective intracellular trafficking of uromodulin mutant isoforms. Traffic. 2006 Nov;7(11):1567-79. doi: 10.1111/j.1600-0854.2006.00481.x. Epub 2006 Sep 30. Citation on PubMed
- Bleyer AJ, Kidd K, Zivna M, Kmoch S. Autosomal Dominant Tubulointerstitial Kidney Disease - UMOD. 2007 Jan 12 [updated 2021 Dec 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1356/ Citation on PubMed
- Hart TC, Gorry MC, Hart PS, Woodard AS, Shihabi Z, Sandhu J, Shirts B, Xu L, Zhu H, Barmada MM, Bleyer AJ. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet. 2002 Dec;39(12):882-92. doi: 10.1136/jmg.39.12.882. Citation on PubMed or Free article on PubMed Central
- Lens XM, Banet JF, Outeda P, Barrio-Lucia V. A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease. Am J Kidney Dis. 2005 Jul;46(1):52-7. doi: 10.1053/j.ajkd.2005.04.003. Citation on PubMed
- Rampoldi L, Caridi G, Santon D, Boaretto F, Bernascone I, Lamorte G, Tardanico R, Dagnino M, Colussi G, Scolari F, Ghiggeri GM, Amoroso A, Casari G. Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics. Hum Mol Genet. 2003 Dec 15;12(24):3369-84. doi: 10.1093/hmg/ddg353. Epub 2003 Oct 21. Citation on PubMed
- Vylet'al P, Kublova M, Kalbacova M, Hodanova K, Baresova V, Stiburkova B, Sikora J, Hulkova H, Zivny J, Majewski J, Simmonds A, Fryns JP, Venkat-Raman G, Elleder M, Kmoch S. Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome. Kidney Int. 2006 Sep;70(6):1155-69. doi: 10.1038/sj.ki.5001728. Epub 2006 Aug 2. Citation on PubMed
- Williams SE, Reed AA, Galvanovskis J, Antignac C, Goodship T, Karet FE, Kotanko P, Lhotta K, Moriniere V, Williams P, Wong W, Rorsman P, Thakker RV. Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum. Hum Mol Genet. 2009 Aug 15;18(16):2963-74. doi: 10.1093/hmg/ddp235. Epub 2009 May 22. Citation on PubMed or Free article on PubMed Central
- Zivna M, Kidd KO, Baresova V, Hulkova H, Kmoch S, Bleyer AJ Sr. Autosomal dominant tubulointerstitial kidney disease: A review. Am J Med Genet C Semin Med Genet. 2022 Sep;190(3):309-324. doi: 10.1002/ajmg.c.32008. Epub 2022 Oct 17. Citation on PubMed
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