The NSRP1-associated disease trait exhibits an autosomal recessive inheritance pattern. Therefore, the pathophysiologic mechanism is presumed loss-of-function (LOF). All patients identified to date have biallelic predicted LOF variants.
Of note, NSRP1 contains a C-terminal nuclear localization signal (NLS, amino acids 531-540) in the final exon required for nuclear localization and splicing activity. As a consequence, LOF variants in the final or penultimate exons which escape nonsense-mediated decay (NMD) may cause disease by disrupting the NLS.
NSRP1