Nephronophthisis: genes and variants

Genes linked to Nephronophthisis

• WDR19: WD repeat-containing protein 19

  Part of the intraflagellar transport A complex, which moves cargo backward through cilia and helps proteins enter the ciliary compartment. By supporting cilium assembly and receptor trafficking, WDR19 contributes to kidney, retinal, skeletal, and reproductive biology.

  7 disease-causing and 55 uncertain variants in WDR19 are linked to Nephronophthisis.

• CEP290: Centrosomal protein of 290 kDa

  It organizes the transition zone of primary and sensory cilia and is essential for ciliary protein trafficking, especially in photoreceptors. Biallelic pathogenic variants cause a broad ciliopathy spectrum including Leber congenital amaurosis, Joubert syndrome, and nephronophthisis-related disease.

  1 disease-causing and 713 uncertain variants in CEP290 are linked to Nephronophthisis.

Weakly linked (only a few uncertain records): IFT172.

Known disease-causing variants in Nephronophthisis

Which prediction tools work for Nephronophthisis

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

• PolyPhen-2: 78 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 75 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 74 out of 100

Same protein, different disease

• Senior-Loken syndrome is also caused by WDR19 variants; they fall mostly in different places as the Nephronophthisis variants (8 disease-causing).
• Asphyxiating thoracic dystrophy 5 is also caused by WDR19 variants; they fall mostly in different places as the Nephronophthisis variants (7 disease-causing).
• CEP290-related ciliopathy is also caused by CEP290 variants; they fall mostly in different places as the Nephronophthisis variants (7 disease-causing).
• Joubert syndrome is also caused by CEP290 variants; they fall mostly in different places as the Nephronophthisis variants (5 disease-causing).

Diseases related to Nephronophthisis

• Senior-Loken syndrome, also linked to CEP290 and WDR19
• Retinitis pigmentosa, also linked to CEP290
• Leber congenital amaurosis, also linked to CEP290
• Bardet-Biedl syndrome, also linked to CEP290
• Connective tissue disorder, also linked to WDR19
• Joubert syndrome, also linked to CEP290
• Asphyxiating thoracic dystrophy 5, also linked to WDR19
• CEP290-related ciliopathy, also linked to CEP290
• Spermatogenic failure 72, also linked to WDR19
• Meckel syndrome, also linked to CEP290
• Meckel-Gruber syndrome, also linked to CEP290
• Cranioectodermal dysplasia, also linked to WDR19

Frequently asked questions

Which genes are linked to Nephronophthisis?

In CATVariant, Nephronophthisis is linked to 2 analyzed proteins: WDR19 (WD repeat-containing protein 19) and CEP290 (Centrosomal protein of 290 kDa).

How many genetic variants are linked to Nephronophthisis?

798 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 769 are of uncertain significance or have conflicting reports.

Which uncertain variants in Nephronophthisis 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 Nephronophthisis?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.74, based on 8 disease-causing and 52 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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