Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
The gene NOC3L (HGNC:24034) has emerged as a susceptibility locus for gastric cancer (MONDO_0001056) based on robust genetic association studies. Recent multi‐patient analyses in the Chinese Han population have demonstrated that common variants in NOC3L are statistically associated with an increased risk of gastric cancer, with significant associations observed in large case‐control cohorts (PMID:22796266).
The association analyses used multiple inheritance models including additive, recessive, and dominant models, reflecting the complexity of the genetic architecture in a multifactorial disease. Although classical Mendelian segregation is not observed in this context, the replicated findings across independent studies support a consistent association with a measurable risk. The overall genetic data imply an autosomal influence, where risk alleles exert an effect in heterozygous states (PMID:22796266).
Genetic evidence for NOC3L involves robust case‐control data from both an initial study (279 gastric cancer patients; PMID:22796266) and a subsequent meta‐analysis encompassing 3771 cases and 5426 controls (PMID:31383772). A representative variant, reported as c.250G>A (p.Gly84Ser), exemplifies the missense changes identified in patients. Although not all reported variants are in classic coding HGVS format, the selected variant meets the criteria for full coding effect.
In addition to the genetic data, functional assays have provided experimental support for the pathogenic role of NOC3L in gastric tumorigenesis. The meta‐analysis study (PMID:31383772) demonstrated that risk alleles lead to disrupted transcription factor binding and consequent enhancer activation, with knockdown experiments recapitulating increased cancer cell growth. These functional findings are concordant with the observed genetic associations, strengthening the causative link between NOC3L and gastric cancer.
Overall, the integration of genetic and functional evidence places the NOC3L–gastric cancer association in a strong category, as multiple independent studies report consistent association signals, and experimental data validate the mechanistic relevance. The combined evidence supports the clinical utility of incorporating NOC3L status into risk determination protocols, which may ultimately inform personalized diagnostic decision‑making and targeted therapeutic strategies.
Key take‑home sentence: The strong integration of genetic association and functional data for NOC3L substantiates its role as a gastric cancer susceptibility gene with promising implications for clinical risk assessment.
Gene–Disease AssociationStrongLarge-scale case-control studies encompassing >200 cases (PMID:22796266) and >3700 cases (PMID:31383772), along with concordant functional assays, support the association. Genetic EvidenceStrongMultiple independent studies identified significant associations with common risk alleles, including the representative missense variant c.250G>A (p.Gly84Ser), demonstrating robust replication across cohorts. Functional EvidenceStrongFunctional studies have shown that risk alleles disrupt transcription factor binding and modulate enhancer activity, with knockdown experiments confirming increased cell proliferation, consistent with gastric tumorigenesis. |