Comprehensively Testing the Function of Missense Variation in the <i>STK11</i> Tumour Suppressor.

ABSTRACT: The tumor suppressor gene STK11 encoding Serine/Threonine Kinase 11 (STK11) is associated with Peutz-Jeghers Syndrome (PJS), a heritable gastrointestinal disease that increases lifetime cancer risk, and with somatic variation that contributes to ~30% of lung and 20% of cervical cancers. Although identifying pathogenic variants is clinically actionable, over 94% of STK11 missense variants that have been observed clinically lack a definitive classification. We therefore measured the impact of STK11 variants at scale in a mammalian cell-based assay, scoring 6,026 (73% of all possible) amino acid substitutions across the full-length gene. Functional scores-which were consistent with biochemical properties, smaller-scale assays, and pathogenicity annotations-identified a su

SUBMITTER: Zimmerman D 

PROVIDER: S-EPMC12338614 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature