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KIAA1549 has been implicated in autosomal recessive retinitis pigmentosa (RP) based on whole exome sequencing of a consanguineous family with two affected siblings and an unrelated case, identifying homozygous variants segregating in two unrelated families (3 probands; 1 additional affected relative) (PMID:30120214). The variants include a missense c.4686C>A (p.His1562Gln) and a frameshift c.52del (p.Arg18fs) affecting both long and short retinal transcripts. These findings provide genetic evidence for a disease mechanism consistent with photoreceptor dysfunction.
Functional studies demonstrated KIAA1549 localization to the photoreceptor connecting cilium and synaptic regions in the mouse retina. Knockdown of the long transcript led to decreased expression of the short, retina-expressed isoform, aligning with the non-syndromic retinal phenotype observed in patients (PMID:30120214). No conflicting reports have been described. Overall, current data yield a limited level of clinical validity for KIAA1549 in RP, with moderate functional support. Testing for KIAA1549 variants can aid diagnosis in unresolved cases of autosomal recessive RP.
Gene–Disease AssociationLimited3 probands in 2 unrelated families with one additional segregating affected sibling and concordant functional data ([PMID:30120214]) Genetic EvidenceLimited3 probands (two siblings and one sporadic case) with segregation evidence in one family ([PMID:30120214]) Functional EvidenceModerateKIAA1549 localises to photoreceptor cilia and synapses; transcript knockdown impairs retinal isoform expression in mouse retina ([PMID:30120214]) |