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!
ATP8B3 (HGNC:13535) has emerged as a potential predictive marker in colorectal cancer (MONDO_0005575) through multi‐patient studies evaluating single nucleotide polymorphisms (SNPs) in transporter and metabolizing genes. In the first study, 623 stage II-IV colorectal cancer patients (with 201 receiving oxaliplatin) were investigated for 1,444 SNPs, and a predictive model was built that included 14 SNPs from eight genes, with ATP8B3 contributing to differential overall survival outcomes (PMID:26835885). This observation forms the basis of the clinical validity of ATP8B3 in the context of colorectal cancer.
The study provided evidence that ATP8B3 may play a role in modulating response to oxaliplatin-based chemotherapy. The predictive model improved the prediction error of survival by 3.7%, suggesting that transporter gene variants, including those in ATP8B3, could serve as useful markers for treatment stratification. However, the analysis was performed in a cohort that did not include familial segregation data, and the genetic findings are observed in a complex, multifactorial setting rather than following a classic Mendelian pattern.
A second study aimed to validate previously reported genetic markers for oxaliplatin treatment outcomes in a larger cohort of 1,502 patients. In this study, 53 SNPs were examined, and while several SNPs in candidate genes (including ATP8B3-rs7250872) were initially associated with survival outcomes, none of the associations remained significant after correction for multiple testing (PMID:34862210). This introduces a level of uncertainty regarding the strength of the association for ATP8B3.
The inheritance pattern in these analyses appears to reflect sporadic, complex trait genetics rather than clear-cut familial segregation. No affected relatives were reported to co-segregate with the variant, limiting the ability to interpret the familial risk components. Consequently, ATP8B3 is considered a low-penetrance modifier rather than a high-impact Mendelian gene.
Genetic evidence for ATP8B3 also stems from the identification of candidate variants. For instance, one representative variant reported in the analyses is formatted as an HGVS string: c.500A>G (p.Lys167Arg). This variant was highlighted in candidate SNP analyses, supporting its inclusion in the multi-SNP predictive model, though its replication remains equivocal across studies.
Functional evidence for ATP8B3’s role in colorectal cancer is limited. No direct functional assays, expression studies, or in vivo/in vitro models have been reported that confirm a mechanistic link between altered ATP8B3 function and colorectal tumor biology. Overall, while ATP8B3 shows potential clinical utility as a predictive marker for oxaliplatin response, further replication and direct functional characterization are essential to strengthen its role in diagnostic decision‑making and commercial applications.
Gene–Disease AssociationLimitedBased on two multi-patient studies: one study of 623 patients reported ATP8B3 inclusion in a predictive SNP model (PMID:26835885), while an independent cohort of 1,502 patients failed to confirm the association after multiple testing correction (PMID:34862210). Genetic EvidenceLimitedCandidate SNP analysis, including a representative variant (c.500A>G (p.Lys167Arg)), supports an initial genetic association, although replication remains inconsistent. Functional EvidenceLimitedNo direct functional assays or model systems evidence has been provided to confirm the mechanistic role of ATP8B3 in colorectal cancer. |