| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Ataxia v2.89 | KIAA0586 | Bryony Thompson Marked gene: KIAA0586 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.89 | KIAA0586 | Bryony Thompson Gene: kiaa0586 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.89 | KIAA0586 | Bryony Thompson Classified gene: KIAA0586 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.89 | KIAA0586 | Bryony Thompson Gene: kiaa0586 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.88 | KIAA0586 |
Bryony Thompson gene: KIAA0586 was added gene: KIAA0586 was added to Ataxia. Sources: Literature Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0586 were set to 40448720; 39898050; 37131188; 36635699; 32381069; 30120217; 26386247; 26386044; 26026149 Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23, MONDO:0014664 Review for gene: KIAA0586 was set to GREEN Added comment: Across nine studies, 33 families (32 independent) with 37 affected individuals have been reported harbouring biallelic loss‑of‑function KIAA0586 variants. All families present the core Joubert syndrome phenotype – cerebellar vermis hypoplasia, molar‑tooth sign, ataxia, developmental delay and hypotonia – with variable additional features such as chronic airway disease, thoracic dysplasia, ocular‑motor apraxia, epilepsy or SUDEP. Autosomal recessive inheritance is consistently demonstrated (e.g., PMID 26026149 box 30, PMID 26386247 box 31). Functional assays show absent KIAA0586 protein or shortened cilia in patient fibroblasts, but no rescue experiments or orthogonal animal models (e.g., PMID 26026149 box 114; PMID 26386247 box 28). A recurrent frameshift allele (c.428delG) is common (gnomAD AF ≈ 0.003) and observed homozygously in healthy individuals, yet is interpreted as a hypomorphic variant that contributes to disease when paired with a second loss‑of‑function allele. No convincing contradictory evidence has been published. The phenotype’s hallmark ataxia makes KIAA0586 a clear fit for the Ataxia panel, which prioritises genes causing disorders where ataxia is a prominent feature. Sources: Literature |
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