STK24 – Keratoconus

In a study of Ecuadorian families with keratoconus, a variant in STK24 showed complete co‑segregation with the disease under an autosomal dominant model (PMID:22045297). Specifically, an intronic change, formatted as c.1053+29G>C (p.?), was identified in one large family, suggesting that STK24 may contribute to keratoconus susceptibility. A subsequent molecular screening study in Polish patients also evaluated STK24 among other candidate genes; however, robust replication of a pathogenic variant in STK24 was not achieved, underscoring the genetic heterogeneity of keratoconus.

Complementary functional data further support the potential role of STK24 in the pathogenesis of keratoconus. In vitro experiments have demonstrated that STK24 (also known as MST3) regulates cellular migration and modulates paxillin phosphorylation, processes that are plausibly linked to the maintenance of corneal structure (PMID:17046825). Together, these genetic and functional findings, although presently limited to a single familial study and supportive cellular assays, provide a biologically plausible framework that may assist in diagnostic decision‑making and inform future targeted screening initiatives.

Key take‑home message: While further replication is required, the integration of segregation data and functional studies indicates that STK24 is a promising candidate gene for keratoconus, with potential utility in clinical diagnostics and commercial genetic screening applications.

References

• European journal of human genetics • 2012 • Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus PMID:22045297
• The Journal of biological chemistry • 2006 • Inhibition of cell migration by autophosphorylated MST3 involves paxillin and protein‑tyrosine phosphatase‑PEST PMID:17046825

Evidence Based Scoring (AI generated)