Familial juvenile hyperuricemic nephropathy type 1: genes and variants

Genes linked to Familial juvenile hyperuricemic nephropathy type 1

• UMOD: Uromodulin

  It is secreted by thick-ascending-limb cells into urine, where it contributes to salt handling, urinary defense, and protection against kidney stones. Dominant pathogenic variants cause autosomal dominant tubulointerstitial kidney disease, while common regulatory variants influence kidney-function and hypertension risk.

  53 disease-causing and 108 uncertain variants in UMOD are linked to Familial juvenile hyperuricemic nephropathy type 1.

• REN: Renin

  It initiates the renin-angiotensin cascade by cleaving angiotensinogen, thereby controlling blood pressure, sodium balance, and extracellular fluid volume. Pathogenic variants can cause renal tubular dysgenesis or rare inherited tubulointerstitial kidney disease depending on their effect on renin production.

  3 disease-causing and 46 uncertain variants in REN are linked to Familial juvenile hyperuricemic nephropathy type 1.

Where Familial juvenile hyperuricemic nephropathy type 1 variants cluster

• UMOD D10C (positions 172–292): 22 of 53 disease-causing changes, 2.2× more than its size predicts.
• UMOD EGF-like 2 (positions 65–107): 11 of 53 disease-causing changes, 3.1× more than its size predicts.
• UMOD EGF-like 4 (positions 292–323): 6 of 53 disease-causing changes, 2.3× more than its size predicts.
• UMOD EGF-like 3 (positions 108–149): 7 of 53 disease-causing changes, 2.0× more than its size predicts.
• UMOD EGF-like 1 (positions 28–64): 6 of 53 disease-causing changes, 2.0× more than its size predicts.

Known disease-causing variants in Familial juvenile hyperuricemic nephropathy type 1

Uncertain variants in Familial juvenile hyperuricemic nephropathy type 1 that look disease-causing

Which prediction tools work for Familial juvenile hyperuricemic nephropathy type 1

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 98 out of 100
• SIFT: 96 out of 100
• PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 85 out of 100

Diseases related to Familial juvenile hyperuricemic nephropathy type 1

• Renal tubular dysgenesis, also linked to REN
• Kidney disorder, also linked to UMOD
• Autosomal dominant medullary cystic kidney disease with or without hyperuricemia, also linked to UMOD
• Renal tubular dysgenesis of genetic origin, also linked to REN
• Chronic kidney disease, also linked to UMOD

Frequently asked questions

Which genes are linked to Familial juvenile hyperuricemic nephropathy type 1?

In CATVariant, Familial juvenile hyperuricemic nephropathy type 1 is linked to 2 analyzed proteins: UMOD (Uromodulin) and REN (Renin).

How many genetic variants are linked to Familial juvenile hyperuricemic nephropathy type 1?

231 variants: 56 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 154 are of uncertain significance or have conflicting reports.

Which uncertain variants in Familial juvenile hyperuricemic nephropathy type 1 look disease-causing?

3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example UMOD C120Y, UMOD C106F and UMOD R204C. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Familial juvenile hyperuricemic nephropathy type 1?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 18 disease-causing and 9 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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