Nephrogenic diabetes insipidus: genes and variants

Genes linked to Nephrogenic diabetes insipidus

• AQP2: Aquaporin-2

  It is inserted into the collecting-duct apical membrane in response to vasopressin, allowing water reabsorption and concentration of urine. Pathogenic variants cause nephrogenic diabetes insipidus, usually recessive for loss-of-function alleles and sometimes dominant through abnormal intracellular trafficking.

  19 disease-causing and 8 uncertain variants in AQP2 are linked to Nephrogenic diabetes insipidus.

• AVPR2: Vasopressin V2 receptor

  7 disease-causing and 0 uncertain variants in AVPR2 are linked to Nephrogenic diabetes insipidus.

Where Nephrogenic diabetes insipidus variants cluster

• AQP2 Discontinuously helical (positions 181–193): 4 of 19 disease-causing changes, 4.4× more than its size predicts.

Known disease-causing variants in Nephrogenic diabetes insipidus

Which prediction tools work for Nephrogenic diabetes insipidus

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

• CATVariant: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 94 out of 100
• phyloP: 91 out of 100
• SIFT: 87 out of 100
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Diabetes insipidus, nephrogenic, autosomal is also caused by AQP2 variants; they fall mostly in different places as the Nephrogenic diabetes insipidus variants (16 disease-causing).
• Diabetes insipidus, nephrogenic, X-linked is also caused by AVPR2 variants; they fall mostly in different places as the Nephrogenic diabetes insipidus variants (25 disease-causing).
• Nephrogenic syndrome of inappropriate antidiuresis is also caused by AVPR2 variants; they fall partly in the same places as the Nephrogenic diabetes insipidus variants (7 disease-causing).

Diseases related to Nephrogenic diabetes insipidus

• Diabetes insipidus, nephrogenic, X-linked, also linked to AVPR2
• Renal tubulopathies, also linked to AVPR2
• Diabetes insipidus, nephrogenic, autosomal, also linked to AQP2
• Autosomal dominant polycystic kidney disease, also linked to AVPR2
• Nephrogenic syndrome of inappropriate antidiuresis, also linked to AVPR2

Frequently asked questions

Which genes are linked to Nephrogenic diabetes insipidus?

In CATVariant, Nephrogenic diabetes insipidus is linked to 2 analyzed proteins: AQP2 (Aquaporin-2) and AVPR2 (Vasopressin V2 receptor).

How many genetic variants are linked to Nephrogenic diabetes insipidus?

104 variants: 26 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 8 are of uncertain significance or have conflicting reports.

Which uncertain variants in Nephrogenic diabetes insipidus look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Nephrogenic diabetes insipidus?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 18 disease-causing and 36 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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