- Structural: it promotes formation of the complex filamentous gel-like organisation that allows water barrier permeability
- In membrane bound form: facilitates neutrophil migration across renal epithelial and may act as a weak ctyokine receptor
- In secreted form contributes to the urine colloid osmotic pressure, slows passage of positively charged ions, prevents crystalisation of supersaturated salts and decreases risk of urinary tract infection
A yet unidentified protease cleaves the 640 peptide protein which releases part of the protein product into the urine and constitutes the most abundant urinary protein in healthy individuals. The aggregated protein is often seen as 'hyaline' urinary casts.
Uromodulin is coded by the UMOD gene at 16p12.3 which has 11 exons and 10 introns. The peptide is N-glycosylated. Genetic defects cause salt wasting and hyperuricaemia with several recognised phenotypes:
- Familial juvenile hyperuricemic nephropathy type 1 (HNFJ1)
- Medullary cystic kidney disease type 2 (MCKD2) with corticomedullary junctional cysts progressing to renal failure in late middle age
- Glomerulocystic kidney disease with hyperuricaemia and isosthenuria (GCKDHI)
Gene variants are associated with:
- Type 2 diabetes mellitus
- Chronic kidney disease, especially forms with interstitial fibrosis
- ↑ Vyletal P, Bleyer AJ, Kmoch S. Uromodulin biology and pathophysiology--an update. Kidney & blood pressure research. 2010; 33(6):456-75.(Link to article – subscription may be required.)
- ↑ TAMM I, HORSFALL FL. A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. The Journal of experimental medicine. 1952 Jan; 95(1):71-97.
- ↑ PERLMANN GE, TAMM I, HORSFALL FL. An electrophoretic examination of a urinary mucoprotein which reacts with various viruses. The Journal of experimental medicine. 1952 Jan; 95(1):99-104.
- ↑ Ahluwalia TS, Lindholm E, Groop L, Melander O. Uromodulin gene variant is associated with type 2 diabetic nephropathy. Journal of hypertension. 2011 Sep; 29(9):1731-4.(Link to article – subscription may be required.)