ANKRD11 is a nuclear transcriptional regulator that modulates gene expression through chr16 remodeling, primarily by recruiting histone deacetylase 3 (HDAC3) to facilitate histone deacetylation at H3K9 and H4K5 1. It functions as a cofactor in transcriptional complexes, interacting with p160 coactivators and nuclear receptors to inhibit ligand-dependent transactivation 2. ANKRD11 plays critical roles in neural precursor cell proliferation and cortical development, and may regulate bone homeostasis and skeletal growth 3. Loss-of-function variants in ANKRD11, predominantly nonsense and frameshift mutations, cause KBG syndrome through haploinsufficiency 4. KBG syndrome presents as a multisystem developmental disorder characterized by distinctive dental features (macrodontia), craniofacial dysmorphism, skeletal abnormalities including short stature (occurring in ~50% of patients), developmental delay, and variable neurodevelopmental complications 5. ANKRD11 variants also contribute to Cornelia de Lange syndrome-like phenotypes and fall within the broader category of chr16—disorders affecting chr16 regulators 6. Genotype-phenotype correlations exist, with sequence variants producing more severe phenotypes than copy number variations, and specific exonic variants associating with particular manifestations such as short stature in exon 9 variants 5. Approximately 42% of developmental disorder cases carry pathogenic de novo mutations in genes like ANKRD11 2.