Autosomal dominant polycystic kidney disease: genes and variants

Genes linked to Autosomal dominant polycystic kidney disease

• PKD2: Polycystin-2

  It provides calcium-permeable polycystin channel activity and forms signaling complexes with polycystin-1 in renal epithelial cells. Loss-of-function variants cause autosomal dominant polycystic kidney disease, generally with a milder average course than PKD1-associated disease.

  6 disease-causing and 359 uncertain variants in PKD2 are linked to Autosomal dominant polycystic kidney disease.

• PKD1: Polycystin-1

  Together with polycystin-2, it participates in tubular signaling, mechanosensation, and maintenance of renal epithelial architecture. Loss-of-function variants are the most common cause of autosomal dominant polycystic kidney disease.

  6 disease-causing and 30 uncertain variants in PKD1 are linked to Autosomal dominant polycystic kidney disease.

• AVPR2: Vasopressin V2 receptor

  0 disease-causing and 0 uncertain variants in AVPR2 are linked to Autosomal dominant polycystic kidney disease.

Where Autosomal dominant polycystic kidney disease variants cluster

• PKD2 Extracellular (positions 242–468): 4 of 6 disease-causing changes, 2.8× more than its size predicts.

Known disease-causing variants in Autosomal dominant polycystic kidney disease

Which prediction tools work for Autosomal dominant polycystic kidney disease

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

• SIFT: 91 out of 100
• CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Polycystic kidney disease is also caused by PKD2 variants; they fall partly in the same places as the Autosomal dominant polycystic kidney disease variants (7 disease-causing).
• Polycystic kidney disease, adult type is also caused by PKD1 variants; they fall mostly in different places as the Autosomal dominant polycystic kidney disease variants (61 disease-causing).

Diseases related to Autosomal dominant polycystic kidney disease

• Polycystic kidney disease, adult type, also linked to PKD1 and PKD2
• Polycystic kidney disease, also linked to PKD1 and PKD2
• Kidney disorder, also linked to PKD1 and PKD2
• Meckel syndrome, also linked to PKD1 and PKD2
• Chronic kidney disease, also linked to PKD1 and PKD2
• Nephrogenic diabetes insipidus, also linked to AVPR2
• Diabetes insipidus, nephrogenic, X-linked, also linked to AVPR2
• Renal tubulopathies, also linked to AVPR2
• Nephrogenic syndrome of inappropriate antidiuresis, also linked to AVPR2

Frequently asked questions

Which genes are linked to Autosomal dominant polycystic kidney disease?

In CATVariant, Autosomal dominant polycystic kidney disease is linked to 3 analyzed proteins: PKD2 (Polycystin-2), PKD1 (Polycystin-1) and AVPR2 (Vasopressin V2 receptor).

How many genetic variants are linked to Autosomal dominant polycystic kidney disease?

436 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 389 are of uncertain significance or have conflicting reports.

Which uncertain variants in Autosomal dominant polycystic kidney disease 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 Autosomal dominant polycystic kidney disease?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 10 disease-causing and 169 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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