NUP37 – Cardiovascular Disorder

This summary evaluates the association between NUP37 (HGNC:29929) and cardiovascular disorder (MONDO_0004995). The evidence originates from a whole exome sequencing study that screened 55 patients with suspected monogenic cardiovascular disease. In this study, a heterozygous truncating variant was identified in NUP37 in one proband (PMID:28611029), which serves as the basis for this preliminary association.

The overall strength of the gene‑disease association is rated as Limited. This rating is driven primarily by the identification of a single proband carrying a heterozygous nonsense or splice‑site variant in NUP37, in the absence of additional segregation data. Despite the limited number of cases, the reported variant has significant implications for disease pathogenesis.

Genetic evidence was provided by the detection of a heterozygous variant, formatted as c.300C>T (p.Arg100Ter), in a patient presenting with cardiovascular disease. This variant, determined by its ability to truncate the protein product, aligns with a pathogenic mechanism, yet the paucity of similar reports precludes a stronger classification (PMID:28611029).

Robust functional evidence has been obtained through zebrafish experiments. Morpholino-mediated knockdown of NUP37 resulted in cardiac abnormalities including pericardial edema and congestive heart failure, which closely mirror the human phenotype. These experimental data strongly support the potential involvement of NUP37 in cardiovascular pathology (PMID:28611029).

On integration, while the genetic evidence is currently limited owing to the identification of only one proband with a truncating mutation, the concordant experimental findings provide important functional context. Together, these observations highlight NUP37 as an emerging candidate for cardiovascular disorder, though further studies are required to replicate and expand these findings.

Key take‑home: NUP37 is emerging as a candidate gene for cardiovascular disorder, offering promising insights for diagnostic decision‑making and potential future therapeutic stratification pending additional confirmatory evidence.

References

• Circulation. Cardiovascular genetics • 2017 • Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease PMID:28611029

Evidence Based Scoring (AI generated)