KIAA1549 was first reported in relation to autosomal recessive retinitis pigmentosa in 2018 (de Bruijn et al., PMID: 30120214). Five homozygous variants (One missense, one nonsense, three frameshift) that have been reported in five probands in four publications (PMIDs: 30120214, 31213501, 36819107, 23105016) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be biallelic loss-of-function.
This gene-disease association is also supported by qPCR experiments showing that KIAA1549 is highly and specifically expressed in the human retina. This same group goes on to use immunofluorescence experiments of mouse retinal sections to show that KIAA1549 is localized to the connecting cilium of photoreceptor cells, and at the outer plexiform layer of the mouse retina (PMID: 30120214). Supporting these results, another mouse model also shows KIAA1549 localization to the outer plexiform layer, as well as in the outer and inner segments of photoreceptor cells (PMID: 34027671).
In summary, KIAA1549 is Strongly associated with autosomal recessive retinitis pigmentosa. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Retina GCEP on February 6, 2025 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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