UMOD

uromodulin

Basic information

Region (hg38): 16:20333051-20356301

Links

ENSG00000169344 ∙ NCBI:7369 ∙ OMIM:191845 ∙ HGNC:12559 ∙ Uniprot:P07911 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glomerulocystic kidney disease with hyperuricemia and isosthenuria (Definitive), mode of inheritance: AD
• autosomal dominant medullary cystic kidney disease with hyperuricemia (Supportive), mode of inheritance: AD
• familial juvenile hyperuricemic nephropathy type 1 (Strong), mode of inheritance: AD
• familial juvenile hyperuricemic nephropathy type 1 (Limited), mode of inheritance: Unknown
• autosomal dominant medullary cystic kidney disease with or without hyperuricemia (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tubulointerstitial kidney disease, autosomal dominant, 1; Glomerulocystic kidney disease with hyperuricemia and isosthenuria	AD	Renal	In Glomerulocystic kidney disease with hyperuricemia and isosthenuria and Tubulointerstitial kidney disease, autosomal dominant, medical treatment may be beneficial (eg, allopurinol related to gout and preservation of renal function)	Renal	7396593; 1975911; 1873940; 9266353; 9686952; 10780922; 12205338; 12471200; 14570709; 12634862; 12629136; 16883323
In some forms of MCKD2, it appears that isolated cysts can occur without hyperuricemia

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UMOD gene.

• not provided (10 variants)
• Familial juvenile hyperuricemic nephropathy type 1 (9 variants)
• Autosomal dominant medullary cystic kidney disease with or without hyperuricemia (2 variants)
• UMOD-related disorder (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UMOD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	51	9	62
missense	13	36	134	9	4	196
nonsense		1	8			9
start loss						0
frameshift			8	1		9
inframe indel	2	1	1	1		5
splice donor/acceptor (+/-2bp)			2			2
splice region			6	5		11
non coding			7	28	24	59
Total	15	38	162	90	37

Variants in UMOD

This is a list of pathogenic ClinVar variants found in the UMOD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-20333052-G-C		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Jan 13, 2018)
16-20333083-T-C		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Jan 12, 2018)
16-20333084-TTAAG-T		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Jun 14, 2016)
16-20333184-G-A		Familial juvenile hyperuricemic nephropathy type 1	Benign (Jan 27, 2021)
16-20333210-G-A		Familial juvenile hyperuricemic nephropathy type 1	Benign (Mar 07, 2020)
16-20333226-C-T		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Jan 13, 2018)
16-20333255-C-T		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Jan 12, 2018)
16-20333275-G-A		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Jan 12, 2018)
16-20333306-G-A		Kidney disorder	Uncertain significance (Dec 12, 2016)
16-20333318-T-C		Familial juvenile hyperuricemic nephropathy type 1	not provided (-)
16-20333321-A-G		not specified • Familial juvenile hyperuricemic nephropathy type 1	Benign/Likely benign (Dec 12, 2023)
16-20333336-G-A		Autosomal dominant medullary cystic kidney disease with or without hyperuricemia • Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Oct 22, 2021)
16-20333338-G-A			Likely benign (Nov 01, 2022)
16-20333341-C-T			Likely benign (Feb 20, 2023)
16-20333342-G-A			Uncertain significance (Mar 25, 2021)
16-20333365-T-C			Likely benign (Aug 07, 2023)
16-20333367-T-C			Uncertain significance (Jul 08, 2023)
16-20333385-A-G			Likely benign (Jan 25, 2024)
16-20333392-G-T			Likely benign (Aug 18, 2023)
16-20333567-C-T			Benign (Jan 06, 2020)
16-20335223-T-C			Benign (Feb 05, 2020)
16-20335472-C-T			Likely benign (Dec 20, 2021)
16-20335483-C-G			Uncertain significance (Oct 12, 2023)
16-20335483-C-CA		Familial juvenile hyperuricemic nephropathy type 1	Uncertain significance (Apr 27, 2017)
16-20335524-T-C			Likely benign (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UMOD	protein_coding	protein_coding	ENST00000570689	10	23250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.08e-17	0.0178	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.998	336	392	0.858	0.0000243	4146
Missense in Polyphen		94	148.41	0.63339		1657
Synonymous	-0.234	180	176	1.02	0.0000130	1251
Loss of Function	0.462	27	29.7	0.909	0.00000154	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00124	0.00124
Ashkenazi Jewish	0.00	0.00
East Asian	0.00212	0.00147
Finnish	0.00	0.00
European (Non-Finnish)	0.000275	0.000273
Middle Eastern	0.00212	0.00147
South Asian	0.000132	0.000131
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Uromodulin: Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water barrier permeability (Probable). May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF (PubMed:3498215). Facilitates neutrophil migration across renal epithelia (PubMed:20798515). {ECO:0000269|PubMed:20798515, ECO:0000269|PubMed:3498215, ECO:0000305}.
• Disease: DISEASE: Familial juvenile hyperuricemic nephropathy 1 (HNFJ1) [MIM:162000]: A renal disease characterized by juvenile onset of hyperuricemia, polyuria, progressive renal failure, and gout. The disease is associated with interstitial pathological changes resulting in fibrosis. {ECO:0000269|PubMed:12471200, ECO:0000269|PubMed:12629136, ECO:0000269|PubMed:12900848, ECO:0000269|PubMed:14569098, ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:15086896, ECO:0000269|PubMed:15575003, ECO:0000269|PubMed:15983957, ECO:0000269|PubMed:17010121, ECO:0000269|PubMed:21060763, ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23197950, ECO:0000269|PubMed:23988501, ECO:0000269|PubMed:25436415}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Medullary cystic kidney disease 2 (MCKD2) [MIM:603860]: A form of tubulointerstitial nephropathy characterized by formation of renal cysts at the corticomedullary junction. It is characterized by adult onset of impaired renal function and salt wasting resulting in end-stage renal failure by the sixth decade. {ECO:0000269|PubMed:12471200, ECO:0000269|PubMed:14531790, ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:17010121, ECO:0000269|PubMed:25436415, ECO:0000269|PubMed:27729211}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI) [MIM:609886]: A renal disorder characterized by a cystic dilation of Bowman space, a collapse of glomerular tuft, and hyperuricemia due to low fractional excretion of uric acid and severe impairment of urine concentrating ability. {ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:17010121}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.245

Intolerance Scores

• loftool: 0.110
• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.8

Haploinsufficiency Scores

• pHI: 0.130
• hipred: N
• hipred_score: 0.208
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.667

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Umod
• Phenotype: immune system phenotype; renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cellular defense response;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;leukocyte cell-cell adhesion;excretion;negative regulation of cell population proliferation;ion homeostasis;metanephric ascending thin limb development;metanephric distal convoluted tubule development;metanephric thick ascending limb development;neutrophil migration
• Cellular component: spindle pole;Golgi lumen;cilium;basolateral plasma membrane;apical plasma membrane;extrinsic component of membrane;anchored component of membrane;ciliary membrane;extracellular exosome
• Molecular function: calcium ion binding;IgG binding