Additional sex combs-like 3 (ASXL3)

Additional sex combs-like 3 (ASXL3) is an epigenetic scaffold protein and transcriptional regulator that plays a critical role in brain and body development. It serves as a core non-catalytic component of the Polycomb Repressive Deubiquitinase (PR-DUB) complex, which modulates gene expression by removing monoubiquitin marks from histone H2A at Lys-119 (H2AK119ub1). Germline loss-of-function mutations in ASXL3 are the primary cause of Bainbridge-Ropers syndrome (BRPS), a rare neurodevelopmental disorder characterized by severe intellectual disability, feeding difficulties, and distinct craniofacial features. Beyond its role in development, ASXL3 is significantly upregulated in certain malignancies, particularly small cell lung cancer (SCLC), where it acts as a pluripotency factor and supports cancer stemness. Therapeutic interest in ASXL3 includes the development of antisense oligonucleotides (ASOs), such as nL-ASXL3-001, which target ASXL3 mRNA to address the underlying genetic cause of Bainbridge-Ropers syndrome. Additionally, research into targeting ASXL3 or its interactions within the PR-DUB complex is being explored as a potential strategy for managing thoracic cancers and other ASXL-related pathologies.

Other names

ASXL Transcriptional Regulator 3Additional Sex Combs-Like Protein 3Putative Polycomb Group Protein ASXL3KIAA1713Bainbridge-Ropers Syndrome ProteinBRPS