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Evidence from case reports and multi‐patient studies has implicated NPAP1 in the etiology of Prader-Willi syndrome (PMID:24311433, PMID:31115529). In these studies, patients presented with cardinal features of the syndrome such as hypogonadism, polyphagia, and truncal obesity. The genomic alterations were identified as deletions within the 15q11‑q13 region that encompass NPAP1 along with neighboring genes like SNRPN and SNORD116. However, due to the overlapping deletion of multiple genes and the mosaic nature of the abnormality, the genetic evidence for NPAP1 as a standalone contributor remains limited. There is also a lack of NPAP1‐specific variant descriptions and segregation data in affected families, which further constrains the strength of the association.
The molecular mechanism is presumed to involve a loss‑of‑function through disruption of an imprinted region, yet no dedicated functional experiments targeting NPAP1 have been reported. Without NPAP1‐specific functional assays, the experimental evidence does not robustly corroborate the genetic data, and the assessment largely depends on the observed genotype–phenotype correlation in a handful of cases. Overall, while NPAP1 is consistently deleted in patients with Prader-Willi syndrome, the limited number of unrelated probands and the involvement of additional genes in the critical region necessitate further research. Key take‑home: Comprehensive genomic evaluation, including refined CNV and functional assessments, is essential to clarify NPAP1’s individual role in Prader-Willi syndrome, thereby enhancing diagnostic precision.
Gene–Disease AssociationLimitedLimited evidence from two independent reports involving one proband each (PMID:24311433, PMID:31115529) with overlapping deletions that include multiple genes. Genetic EvidenceLimitedGenetic evidence derives from copy number studies with deletions encompassing NPAP1 among other regional loci, and no NPAP1‐specific variants have been delineated. Functional EvidenceLimitedNo NPAP1‐specific functional assays or experimental models have been reported to support a direct functional role in Prader-Willi syndrome. |