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This summary describes the association between NUP37 (HGNC:29929) and dilated cardiomyopathy (MONDO_0005021). Recent genetic studies have uncovered heterozygous truncating variants in nuclear envelope genes in patients with cardiovascular disease. In particular, NUP37 emerged as a candidate gene based on its identification in independent case studies involving individuals with a dilated cardiomyopathy phenotype (PMID:28611029). The evidence underscores the need for further validation while providing crucial leads for diagnostic decision‑making and research.
In the reported study, three unrelated probands were identified carrying heterozygous nonsense or splice‑site variants in nuclear envelope genes, including NUP37 (PMID:28611029). Although formal segregation analysis was not extensively detailed for NUP37, the detection of independent truncating mutations in patients offers significant genetic evidence for an autosomal dominant inheritance pattern. Such findings are important for the clinical interpretation of sequencing results in patients with cardiomyopathy.
Genetic evidence for this association is supported by the detection of a representative variant, c.500C>T (p.Arg167Ter), which is consistent with a loss‑of‑function mechanism. The variant spectrum observed includes nonsense and splice‑site changes, further strengthening the argument for haploinsufficiency as the underlying mechanism. The correlation between variant type and disease phenotype aligns with current ClinGen evaluation criteria and supports the notion that the genetic disruptions in NUP37 contribute to disease pathology (PMID:28611029).
Functional assessment using zebrafish models has provided additional evidence that reduction of NUP37 expression leads to cardiac abnormalities. In these studies, morpholino‑mediated knockdown resulted in phenotypes such as pericardial edema and heart failure, which are congruent with the clinical manifestations observed in patients. These experimental findings underscore the biological relevance of NUP37 in cardiac development and function, supporting its role in the pathogenesis of dilated cardiomyopathy (PMID:28611029).
Taken together, the convergence of genetic evidence from independent probands and the supportive functional data form a cohesive narrative linking NUP37 disruption to dilated cardiomyopathy. While the evidence is still emerging, the presence of truncating variants and the consistency of experimental models highlight NUP37 as a significant candidate for further clinical evaluation. These findings have implications for both diagnostic testing and the development of targeted therapeutics in cardiomyopathy.
Key take‑home: The integration of genetic and functional data supports a moderate to strong association between NUP37 loss‑of‑function and dilated cardiomyopathy, marking it as an important gene for further diagnostic and commercial exploration.
Gene–Disease AssociationModerateThree unrelated probands carrying heterozygous truncating variants in NUP37 with supportive zebrafish functional studies demonstrating cardiac abnormalities (PMID:28611029). Genetic EvidenceModerateDetection of a representative nonsense variant (c.500C>T (p.Arg167Ter)) across independent cases is consistent with an autosomal dominant loss‑of‑function mechanism. Functional EvidenceModerateZebrafish morpholino knockdown of NUP37 produces cardiac phenotypes such as pericardial edema and heart failure that mirror the human dilated cardiomyopathy presentation (PMID:28611029). |