Uromodulin

From Ganfyd

Uromodulin, or eponymously Tamm-Horsfall protein is a mucoprotein produced and expressed in the thick limb of the loop of Henle where it is thought to serve a number of functions.^[1] These include:

1. Structural: it promotes formation of the complex filamentous gel-like organisation that allows water barrier permeability
2. Functional:
   • 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.

Described in 1952 by Igor Tamm and Frank Horsfall.^[2][3] Urinary uromodulin is a potential marker of renal disease.

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^[4]:

• Hypertension
• Type 2 diabetes mellitus
• Chronic kidney disease, especially forms with interstitial fibrosis

References