Senior-Loken syndrome: genes and variants

Genes linked to Senior-Loken syndrome

• 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.

  8 disease-causing and 399 uncertain variants in WDR19 are linked to Senior-Loken syndrome.

• 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 123 uncertain variants in CEP290 are linked to Senior-Loken syndrome.

Known disease-causing variants in Senior-Loken syndrome

Which prediction tools work for Senior-Loken syndrome

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

• AlphaMissense: 100 out of 100
• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 92 out of 100
• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 84 out of 100
• MetaLR: 79 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Asphyxiating thoracic dystrophy 5 is also caused by WDR19 variants; they fall mostly in different places as the Senior-Loken syndrome variants (7 disease-causing).
• Nephronophthisis is also caused by WDR19 variants; they fall mostly in different places as the Senior-Loken syndrome variants (7 disease-causing).
• Spermatogenic failure 72 is also caused by WDR19 variants; they fall mostly in different places as the Senior-Loken syndrome variants (3 disease-causing).
• CEP290-related ciliopathy is also caused by CEP290 variants; they fall mostly in different places as the Senior-Loken syndrome variants (7 disease-causing).
• Joubert syndrome is also caused by CEP290 variants; they fall mostly in different places as the Senior-Loken syndrome variants (5 disease-causing).

Diseases related to Senior-Loken syndrome

• Nephronophthisis, 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 Senior-Loken syndrome?

In CATVariant, Senior-Loken syndrome 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 Senior-Loken syndrome?

566 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 522 are of uncertain significance or have conflicting reports.

Which uncertain variants in Senior-Loken syndrome 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 Senior-Loken syndrome?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 8 disease-causing and 13 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center