KIFC1 – Primary Ciliary Dyskinesia

In early candidate gene studies, KIFC1 (HGNC:6389) was investigated for its potential role in primary ciliary dyskinesia (MONDO_0016575). An Immunogenetics study (PMID:10369922) examined two ICS families and identified four single base substitutions in the HSET gene, but concluded that the HSET product (KIFC1) was unlikely to contribute to disease pathogenesis. This initial evidence did not offer sufficient support for a pathogenic role, as the study noted the absence of convincing segregation or functional validation in the affected families (PMID:10369922).

A subsequent multi‐patient analysis in a Tunisian cohort screened for mutations across a panel of primary ciliary dyskinesia genes, including KIFC1. Although this study successfully identified bi‐allelic mutations in other key genes (for example, a recurrent founder mutation in CCDC39 and deleterious variants in DNAH5) (PMID:31469207), no definitive pathogenic variants in KIFC1 were reported. In the absence of robust segregation data, recurrent or clearly deleterious variants, and corroborative functional evidence, the cumulative data do not support the clinical utility of KIFC1 in diagnosing primary ciliary dyskinesia. Key take‑home: The current genetic and experimental evidence for KIFC1 in primary ciliary dyskinesia is disputed, and additional investigation is required before it can be applied in diagnostic or commercial settings.

References

• Immunogenetics • 1999 • Genomic organization of the HSET locus and the possible association of HLA‑linked genes with immotile cilia syndrome PMID:10369922
• Human Mutation • 2020 • Primary ciliary dyskinesia gene contribution in Tunisia: Identification of a major Mediterranean allele PMID:31469207

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