ANKRD11

ANKRD11 (ankyrin repeat domain-containing protein 11) is a protein-coding gene in humans. The ANKRD11 protein contains multiple ankyrin repeat motifs and functions as a transcriptional co-regulator, contributing to chromatin remodeling and gene expression regulation. It localizes to the nucleus and participates in multiprotein complexes that control transcriptional activity during development.

Genetics and structure: ANKRD11 is located on chromosome 16q24.3. Pathogenic variants include haploinsufficient truncating variants and intragenic deletions that disrupt the gene, as well as microdeletions that remove ANKRD11. Most cases arise de novo, with autosomal dominant inheritance.

Clinical significance: Pathogenic variants in ANKRD11 cause KBG syndrome, a neurodevelopmental disorder characterized by distinctive facial features, skeletal anomalies, short stature, and developmental delays. A hallmark feature is macrodontia of maxillary permanent central incisors. Patients may exhibit intellectual disability or learning difficulties, speech delay, seizures, and autistic features, with variable expressivity. Behavioral issues and language impairment are common. The syndrome is typically milder in individuals with deletions not including other genes, and more variable when larger 16q24.3 deletions are involved.

Diagnosis and management: Diagnosis is based on clinical features with molecular confirmation of ANKRD11 variants or deletions. Management is multidisciplinary, addressing growth, dental anomalies, communication, orthopedic and developmental needs.

Research and discovery: ANKRD11 functions as a transcriptional co-regulator, interacting with chromatin modifiers to regulate gene expression during development. Animal models and patient-derived data are used to study its role in neurodevelopment and craniofacial morphogenesis.