Paired box protein Pax-6 (PAX6) (PAX6)

Paired box protein Pax-6 (PAX6) is a master regulatory transcription factor essential for the development of the eyes, brain, and pancreas (UniProt P26367). It contains two distinct DNA-binding domains—a paired domain and a homeodomain—that allow it to regulate a vast network of genes involved in cell proliferation and differentiation (PubMed: 26058356). Mutations in the PAX6 genomic locus, particularly nonsense mutations leading to haploinsufficiency, are the primary cause of aniridia, a condition characterized by the partial or total absence of the iris and progressive vision loss (NIH GARD). The genomic PAX6 mutant locus is a specific target for precision medicines, including nonsense-mediated read-through drugs like ataluren and ELX-02, which aim to bypass premature stop codons and restore functional protein production (PubMed: 31515530). Additionally, gene-editing approaches such as CRISPR/Cas9 are being explored to directly correct mutations at the genomic level (PubMed: 30103477). Because PAX6 is highly dosage-sensitive, therapeutic interventions must be carefully controlled to avoid the developmental defects associated with both protein deficiency and overexpression (PubMed: 22135242).

Other names

AN2Aniridia type II proteinOculorhombinPAX-6

Nonsense mutation read-through and gene correction