UMOD
Uromodulin (Tamm-Horsfall Protein) Gene
Gene Information Card
| Symbol | UMOD |
|---|---|
| Full Name | Uromodulin |
| Gene Type | Protein coding |
| Chromosomal Location | 16p12.3 |
| NCBI Gene ID | 7369 ncbi.nlm.nih.gov/gene/7369 |
| Ensembl ID | ENSG00000169344 |
| UniProt ID | P07911 |
| OMIM ID | 191845 |
| HGNC ID | 12559 |
| Aliases | THP, Tamm-Horsfall protein, uromucoid |
Description
The UMOD gene encodes uromodulin, also known as Tamm-Horsfall protein, the most abundant protein in normal human urine. It is synthesized exclusively in the thick ascending limb of the loop of Henle and early distal convoluted tubule of the kidney. Uromodulin plays critical roles in preventing urinary tract infections, regulating salt and water homeostasis, and protecting against kidney stone formation. Mutations in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), characterized by hyperuricemia, gout, and progressive renal failure.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) | Missense mutations lead to misfolded uromodulin, causing endoplasmic reticulum retention, tubular cell toxicity, and progressive fibrosis. | ClinVar, OMIM #191845 |
| Familial juvenile hyperuricemic nephropathy (FJHN) | Same mechanism as ADTKD-UMOD; defective uromodulin secretion impairs urate excretion, leading to hyperuricemia and gout. | OMIM #162000 |
| Glomerulocystic kidney disease (GCKD) | Mutations in UMOD cause cystic dilation of Bowman's space and glomerular cysts, often presenting in childhood. | OMIM #609886 |
| Urolithiasis (kidney stones) | Reduced urinary uromodulin concentration may promote calcium oxalate crystal aggregation and stone formation. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 1256.5 | High |
| Liver | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HK-2 (kidney proximal tubule) | 0.0 | Not expressed (cell line origin differs from thick ascending limb) |
| HEK293 (embryonic kidney) | 0.0 | Not expressed endogenously; used for recombinant expression |
| Primary renal tubular epithelial cells | Variable | Low to moderate depending on differentiation state |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.151T>C (p.Cys51Arg) | Missense | Rare | Loss of function; ER retention |
| c.208T>C (p.Cys70Arg) | Missense | Rare | Loss of function; ER retention |
| c.509C>T (p.Thr170Met) | Missense | Common in ADTKD | Loss of function; impaired trafficking |
| c.674G>A (p.Arg225Gln) | Missense | Rare | Loss of function; reduced secretion |
Mutation functional classification
Loss of Function (LOF)
Most UMOD mutations are missense causing misfolding, ER retention, and reduced secretion of uromodulin, leading to loss of normal function in the urine.
Gain of Function (GOF)
No gain-of-function mutations have been described for UMOD.
Dominant Negative (DN)
Mutant uromodulin is thought to exert a dominant-negative effect by forming aggregates with wild-type protein, impairing its secretion and causing tubular cell toxicity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Uromodulin trafficking and maturation (REACTOME)
• Defective uromodulin causes ADTKD (KEGG hsa05200)
Protein Summary
Uromodulin (Tamm-Horsfall protein) is a 640-amino acid glycoprotein with a molecular weight of approximately 85-95 kDa. It is synthesized as a precursor with a 24-amino acid signal peptide. The mature protein contains three epidermal growth factor (EGF)-like domains, a zona pellucida (ZP) domain, and a glycosylphosphatidylinositol (GPI) anchor that attaches it to the apical plasma membrane of thick ascending limb cells. Uromodulin is cleaved and released into urine, where it forms high-molecular-weight polymers. It functions as a constitutive defense against urinary tract infections by binding to type 1 fimbriated Escherichia coli, and it modulates immune responses via Toll-like receptor 4 activation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UMODL1 Knockout HEK293 Cell Line | EDJ-KQ9773 | Human | 89766 | Details Get a Quote |
| UMOD Knockout HEK293 Cell Line | EDJ-KQ16030 | Human | 7369 | Details Get a Quote |
| Umod Knockout RAW 264.7 Cell Line | EDJ-KZ75 | Mouse | 22242 | Details Get a Quote |
| UMOD Knockout HeLa Cell Line | EDJ-KQ54728 | Human | 7369 | Details Get a Quote |
| UMODL1 Knockout HeLa Cell Line | EDJ-KQ57734 | Human | 89766 | Details Get a Quote |
| UMOD Knockout A-549 Cell Line | EDJ-KQ63220 | Human | 7369 | Details Get a Quote |
| UMODL1 Knockout A-549 Cell Line | EDJ-KQ66230 | Human | 89766 | Details Get a Quote |
| UMOD Knockout HCT 116 Cell Line | EDJ-KQ71685 | Human | 7369 | Details Get a Quote |
| UMODL1 Knockout HCT 116 Cell Line | EDJ-KQ74652 | Human | 89766 | Details Get a Quote |
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