Nup98

NUP98 is a nucleoporin protein in humans encoded by the NUP98 gene. It is a component of the nuclear pore complex (NPC) that lines the nuclear envelope and mediates selective transport between the nucleus and cytoplasm. The protein is characterized by an abundance of FG repeats, including GLFG motifs, which interact with transport receptors to facilitate cargo docking and translocation through the NPC. In vertebrates, NUP98 is produced as part of a precursor that is cleaved to yield the mature NUP98 and NUP96 subunits, both of which localize to the NPC.

Functionally, NUP98 participates in nucleocytoplasmic transport, contributing to mRNA export and the trafficking of proteins and ribonucleoprotein particles. Beyond transport, it has been implicated in gene regulation and chromatin organization in some cellular contexts, though its primary validated role remains transport through the NPC.

Clinical significance of NUP98 centers on chromosomal rearrangements that involve the gene. NUP98 is one of the more frequently rearranged nucleoporin genes in hematologic malignancies, particularly acute myeloid leukemia and myelodysplastic syndromes. Fusion genes such as NUP98-HOXA9 and NUP98-NSD1 arise from these rearrangements and are associated with dysregulated transcription and leukemogenesis. The diverse NUP98 fusion partners contribute to differing clinical outcomes, but these rearrangements generally indicate aggressive disease in affected patients.

Evolutionarily, NUP98 is conserved across eukaryotes and fits the broader pattern of FG-repeat nucleoporins that form the selective barrier of the NPC and interact with transport receptors to coordinate nucleocytoplasmic trafficking.