In an extremely rare genetic disease called congenital brachyphalangy and also in polydactyly and tibial aplasia/hypoplasia syndrome (BPTA syndrome), a frameshift variant in the acidic tail of HMGB1 alters HMGB1 phase separation and enhances its partitioning into the nucleolus, which results in nucleolar dysfunction and eventually, body development disorders (23). This evidence concerns the gene HMGB1 and hereditary disease.