UMOD uromodulin [Homo sapiens (human)] - Gene

Summary

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Official Symbol: UMODprovided by HGNC
Official Full Name: uromodulinprovided by HGNC
Primary source: HGNC:12559
See related: Ensembl:ENSG00000169344; HPRD:11771; MIM:191845; Vega:OTTHUMG00000131488
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: THP; FJHN; HNFJ; THGP; HNFJ1; MCKD2; ADMCKD2
Summary: This gene encodes uromodulin, the most abundant protein in normal urine. Its excretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. Uromodulin may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of uromodulin in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the autosomal dominant renal disorders medullary cystic kidney disease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN). These disorders are characterized by juvenile onset of hyperuricemia, gout, and progressive renal failure. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 16p12.3

Sequence :: Chromosome: 16; NC_000016.9 (20344373..20364037, complement)

See UMOD in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

The rs12917707 minor allele showed association with lower risk of end-stage renal disease.
Title: UMOD as a susceptibility gene for end-stage renal disease.
uromodulin is a NLRP3 agonist handled by antigen-presenting cells as an immunostimulatory nanoparticle
Title: Uromodulin triggers IL-1β-dependent innate immunity via the NLRP3 inflammasome.
The present study reported a novel mutation in exon 9 of UMOD in the Chinese Han population, within the GPI anchor signal segment of uromodulin.
Title: Novel uromodulin mutation in familial juvenile hyperuricemic nephropathy.
It was shown that common variants of uromodulin are associated with diastolic blood pressure in a community-based Chinese cohort. Urinary uromodulin was correlated with urinary sodium.
Title: Common variants of the UMOD promoter associated with blood pressure in a community-based Chinese cohort.
association of estimated glomerular filtration rate and urinary uromodulin concentrations with rare variants in UMOD gene
Title: Association of estimated glomerular filtration rate and urinary uromodulin concentrations with rare variants identified by UMOD gene region sequencing.
Both in vitro and in vivo, mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein.
Title: Urinary secretion and extracellular aggregation of mutant uromodulin isoforms.
The indel mutation is associated with a relatively mild clinical UMOD-associated kidney disease (UAKD) phenotype.
Title: Characterization of a recurrent in-frame UMOD indel mutation causing late-onset autosomal dominant end-stage renal failure.
The detection of uromodulin mutants, using the C148W mutant as a target molecule, is reported.
Title: Detection of mutant uromodulin in transgenic mouse harboring a mutant human UMOD gene.
Molecular and cellular effects of Tamm-Horsfall protein mutations and their rescue by chemical chaperones.
Title: Molecular and cellular effects of Tamm-Horsfall protein mutations and their rescue by chemical chaperones.
Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation.
Title: Phenotype and outcome in hereditary tubulointerstitial nephritis secondary to UMOD mutations.

Submit: New GeneRIF Correction See all (64)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

UMOD-associated kidney disease (uromodulin-associated kidney disease) is also known as familial juvenile hyperuricemic nephropathy type 1 (FJHN1) and medullary cystic kidney disease type 2 (MCKD2). Clinical findings typically include hyperuricemia and gout (resulting from reduced kidney excretion of uric acid) that usually occur as early as the teenage years. Slowly progressive interstitial kidney disease begins early in life. Elevations in serum creatinine usually occur between ages five and 40 years, leading to end-stage kidney disease (ESRD) usually between the fourth and seventh decade. The age at ESRD varies both between and within families.

Diagnosis Testing

UMOD-associated kidney disease is defined by the presence of a mutation in UMOD, the gene encoding uromodulin (also known as Tamm Horsfall protein). UMOD molecular genetic testing is clinically available. Elevated serum uric acid concentration and reduced fractional excretion of urate are often, but not always, found. Renal ultrasound examination usually shows normal or small-sized kidneys. Of note, medullary cysts (i.e., in the medulla or at the corticomedullary junction) are a late finding and may not be seen on imaging studies because of their small size.

Genetic Counseling

UMOD-associated kidney disease is inherited in an autosomal dominant manner. Most individuals diagnosed with UMOD-associated kidney disease have an affected parent. Each child of an affected individual has a 50% chance of inheriting the mutation. Prenatal testing is available for pregnancies at increased risk in families in which the disease-causing mutation has been identified. Requests for prenatal testing for conditions such as UMOD-associated kidney disease that do not affect intellect and have treatment available are not common.

References

PMID: 20301530

Glomerulocystic kidney disease with hyperuricemia and isosthenuria

MIM: 609886

Genetic Testing Registry

Summary from GeneReviews: UMOD-Associated Kidney Disease

Disease Characteristics

UMOD-associated kidney disease (uromodulin-associated kidney disease) is also known as familial juvenile hyperuricemic nephropathy type 1 (FJHN1) and medullary cystic kidney disease type 2 (MCKD2). Clinical findings typically include hyperuricemia and gout (resulting from reduced kidney excretion of uric acid) that usually occur as early as the teenage years. Slowly progressive interstitial kidney disease begins early in life. Elevations in serum creatinine usually occur between ages five and 40 years, leading to end-stage kidney disease (ESRD) usually between the fourth and seventh decade. The age at ESRD varies both between and within families.

Diagnosis Testing

UMOD-associated kidney disease is defined by the presence of a mutation in UMOD, the gene encoding uromodulin (also known as Tamm Horsfall protein). UMOD molecular genetic testing is clinically available. Elevated serum uric acid concentration and reduced fractional excretion of urate are often, but not always, found. Renal ultrasound examination usually shows normal or small-sized kidneys. Of note, medullary cysts (i.e., in the medulla or at the corticomedullary junction) are a late finding and may not be seen on imaging studies because of their small size.

Genetic Counseling

UMOD-associated kidney disease is inherited in an autosomal dominant manner. Most individuals diagnosed with UMOD-associated kidney disease have an affected parent. Each child of an affected individual has a 50% chance of inheriting the mutation. Prenatal testing is available for pregnancies at increased risk in families in which the disease-causing mutation has been identified. Requests for prenatal testing for conditions such as UMOD-associated kidney disease that do not affect intellect and have treatment available are not common.

References

PMID: 20301530

Medullary cystic kidney disease 2

MIM: 603860

Genetic Testing Registry

Summary from GeneReviews: UMOD-Associated Kidney Disease

Disease Characteristics

UMOD-associated kidney disease (uromodulin-associated kidney disease) is also known as familial juvenile hyperuricemic nephropathy type 1 (FJHN1) and medullary cystic kidney disease type 2 (MCKD2). Clinical findings typically include hyperuricemia and gout (resulting from reduced kidney excretion of uric acid) that usually occur as early as the teenage years. Slowly progressive interstitial kidney disease begins early in life. Elevations in serum creatinine usually occur between ages five and 40 years, leading to end-stage kidney disease (ESRD) usually between the fourth and seventh decade. The age at ESRD varies both between and within families.

Diagnosis Testing

UMOD-associated kidney disease is defined by the presence of a mutation in UMOD, the gene encoding uromodulin (also known as Tamm Horsfall protein). UMOD molecular genetic testing is clinically available. Elevated serum uric acid concentration and reduced fractional excretion of urate are often, but not always, found. Renal ultrasound examination usually shows normal or small-sized kidneys. Of note, medullary cysts (i.e., in the medulla or at the corticomedullary junction) are a late finding and may not be seen on imaging studies because of their small size.

Genetic Counseling

UMOD-associated kidney disease is inherited in an autosomal dominant manner. Most individuals diagnosed with UMOD-associated kidney disease have an affected parent. Each child of an affected individual has a 50% chance of inheriting the mutation. Prenatal testing is available for pregnancies at increased risk in families in which the disease-causing mutation has been identified. Requests for prenatal testing for conditions such as UMOD-associated kidney disease that do not affect intellect and have treatment available are not common.

References

PMID: 20301530

NHGRI GWAS Catalog

Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases.

Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass.

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Multiple loci associated with indices of renal function and chronic kidney disease.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P07911	P01374	LTA	HPRD	PubMed
P07911	P22894	MMP8	HPRD	PubMed
BioGRID:113216	BioGRID:110227	LTA	BioGRID	PubMed	Reconstituted Complex

General gene information

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Markers

D16S3113 (e-PCR)
- UniSTS:65089

D16S401 (e-PCR), detects polymorphism
- UniSTS:77403

D16S500 (e-PCR)
- UniSTS:15759

D16S3036 (e-PCR)
- UniSTS:29087

D16S3217 (e-PCR)
- UniSTS:1443

Genotypes

See UMOD SNP Geneview Report
See UMOD SNP Genotype Report
See UMOD SNP Variation Viewer Report

Homology

Homologs of the UMOD gene: The UMOD gene is conserved in Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cellular defense response	TAS Traceable Author Statement more info	PubMed
chemical homeostasis	IEA Inferred from Electronic Annotation more info
excretion	IEA Inferred from Electronic Annotation more info
metanephric ascending thin limb development	IEA Inferred from Electronic Annotation more info
metanephric distal convoluted tubule development	IEA Inferred from Electronic Annotation more info
metanephric thick ascending limb development	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
regulation of ion homeostasis	IEA Inferred from Electronic Annotation more info
response to organic substance	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	IEA Inferred from Electronic Annotation more info
anchored to membrane	IDA Inferred from Direct Assay more info
apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
cilium membrane	IEA Inferred from Electronic Annotation more info
cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
extracellular space	IEA Inferred from Electronic Annotation more info
extrinsic to membrane	TAS Traceable Author Statement more info	PubMed
membrane raft	IEA Inferred from Electronic Annotation more info
primary cilium	IDA Inferred from Direct Assay more info
spindle pole	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: uromodulin

Names: uromodulin; uromucoid; Tamm-Horsfall glycoprotein; tamm-Horsfall urinary glycoprotein; uromodulin (uromucoid, Tamm-Horsfall glycoprotein)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008151.1 RefSeqGene

Range

5001..24665

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001008389.1 → NP_001008390.1 uromodulin precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform.

Source sequence(s)

AK091961, BC035975, BF593229, BG428950

Consensus CDS

CCDS10583.1

UniProtKB/Swiss-Prot

P07911

Related

ENSP00000306279, ENST00000302509

Conserved Domains (3) summary

cd00054
Location:108 – 149
Blast Score: 102

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

smart00241
Location:334 – 583
Blast Score: 544

ZP; Zona pellucida (ZP) domain

pfam12947
Location:35 – 63
Blast Score: 102

EGF_3; EGF domain
NM_003361.2 → NP_003352.2 uromodulin precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 encode the same isoform.

Source sequence(s)

AK091961, BC035975, BF593229, BG428950

Consensus CDS

CCDS10583.1

UniProtKB/Swiss-Prot

P07911

Related

ENSP00000379446, ENST00000396142

Conserved Domains (3) summary

cd00054
Location:108 – 149
Blast Score: 102

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

smart00241
Location:334 – 583
Blast Score: 544

ZP; Zona pellucida (ZP) domain

pfam12947
Location:35 – 63
Blast Score: 102

EGF_3; EGF domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p10 Primary Assembly

Range

20344373..20364037, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

18881007..18900693, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018927.1 Alternate CHM1_1.0

Range

20347492..20367239, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01028278.1 (168895..188581)	None
genomic	AC106796.3 (100572..120236)	None
genomic	AMYH01007328.1 (147011..147992)	None
genomic	AMYH01007329.1	None
genomic	AY061638.1	AAL27853.1
genomic	AY162970.1	AAO64446.1
genomic	CH471186.1	EAW50314.1
		EAW50315.1
mRNA	AK055722.1	BAG51560.1
mRNA	AK091961.1	BAG52451.1
mRNA	AK096043.1	BAG53202.1
mRNA	AK127643.1	BAC87070.1
mRNA	AK127648.1	BAG54541.1
mRNA	BC035975.1	AAH35975.1
mRNA	BF593229.1	None
mRNA	BG428950.1	None
mRNA	M15881.1	AAA36798.1
mRNA	M17778.1	AAA36799.1