NIPBL

The protein functions as a cohesin loading factor that facilitates sister chromatid cohesion and enables enhancer-promoter communication for proper developmental gene regulation. Loss-of-function mutations cause Cornelia de Lange syndrome 1, an autosomal dominant disorder characterized by distinctive facial features, growth delay, limb defects, and intellectual disability. The high intolerance to loss-of-function variants (pLI=1) reflects the protein's essential role in chromatin organization and gene expression during development.