An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somite organization

Proceedings of the National Academy of Sciences, Volume 122, Number 49, December 2025.
ImportanceIMPDH2 is an essential enzyme for de novo purine biosynthesis, regulating the balance between adenine and guanine nucleotides. Under purine stress, it forms filaments that resist feedback inhibition by GTP. Patients with gain of function…