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About Uromodulin / UMOD:

Uromodulin, also frequently called Tamm-Horsfall glycoprotein, is a type of protein found excreted in the urine.

Uromodulin Function
While the precise function of uromodulin is still being investigated, researchers believe that it plays a prominent role in the prevention of calcium crystallization in renal fluids. Investigations have shown that the body excretes uromodulin after the cleavage of ectodomain from its glycophosphatidylinositol-anchored substrate. It may, therefore, also play a role as an antipathogenic agent, preventing the development of urinary tract infections.
Like many proteins in its class, uromodulin probably has multiple functions that co-evolved to solve a diverse range of problems in living organisms. Uromodulin, for instance, might have a role in transporter function. Mice that do not produce normal levels of uromodulin find it challenging to regulate their physiology.
The protein may also help with bacterial binding. Studies suggest that uromodulin may be able to trap E. coli bacteria in the urinary tract using special bacterial binding mannose-containing side chains.

UMOD Mechanism
Unlike many glycoproteins, uromodulin is not made in the blood plasma. Instead, it is made in the loop of Henle in the thick, ascending limb (in mammals).
Instructions for the creation of uromodulin in humans are located on the UMOD gene on chromosome 16. There are several varieties of this gene, but there are only two that have been shown to encode for uromodulin in the same isoform fully. Others may play supporting roles.
Uromodulin has potential clinical significance because of its relationship with kidney stones. Some researchers believe that uromodulin may assist the formation of the matrix in renal calculi, but whether it is an active agent in this process remain to be seen. It is not clear if uromodulin inhibitors would have any clinically significant benefits for people with a predisposition for the condition. Research to date suggests that elevated levels of uromodulin are associated with a higher chance of kidney stones, but whether the relationship is causative is yet to be determined.
Defects in the UMOD gene (that programs for uromodulin production in the loop of Henle) are, however, associated with a range of adverse medical conditions. People with certain forms of the gene (often hereditary) can develop familial juvenile hyperuricemic nephropathy. The genetic condition dramatically increases the likelihood that the person will go on to develop chronic diseases such as kidney failure, gout, and hyperuricemia.
Problems with the UMOD gene also cause autosomal dominant tubulointerstitial kidney disease, which leads to chronic kidney disease. People who have variants of the UMOD gene are much more likely to have hypertension and kidney stones, compared to the normal, healthy age-matched adult population.
Uromodulin is exclusively produced in the kidney and is the most abundant protein in the urine. It has become a greater focus of clinical research over recent years, owing to its apparent involvement in the pathology and development of chronic kidney disease. Many researchers now suspect that it is an essential biomarker for a range of renal-related problems. While defects in the UMOD gene are rare, they could explain cases of hypertension that do not respond to conventional therapies.