BMI1

This protein is a core component of the polycomb repressive complex 1 (PRC1) that maintains transcriptional silencing of developmental genes through chromatin remodeling and histone modification, particularly monoubiquitination of histone H2A. Mutations cause autosomal dominant primary microcephaly with early-onset seizures and developmental delay, reflecting the gene's critical role in neurodevelopment. The gene is highly constrained against loss-of-function variants (pLI = 0.94), consistent with the severe neurological phenotype observed in affected patients.