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Recent pharmacogenomic analyses have included PACSIN2 (HGNC:8571) as a candidate gene when investigating adverse drug reactions in pediatric acute lymphoblastic leukemia (MONDO_0004967). Two multi‐patient studies evaluated a panel of genes to determine predictors of 6‑mercaptopurine/methotrexate intolerance during maintenance therapy. Although PACSIN2 was part of the candidate gene set, its variants did not show statistically significant associations with treatment tolerance when compared to other genes such as SLCO1B1 and NUDT15 (PMID:29683944, PMID:32221476).
The genetic evidence is limited by the absence of robust variant‐level correlations and pedigree segregation data. None of the studies demonstrated additional affected relatives harboring PACSIN2 variants nor provided detailed variant spectra specific to this gene. In the evaluated cohorts, the PACSIN2 variant contribution was overshadowed by more prominent markers, thereby rendering its clinical utility uncertain.
Functional and experimental evidence for PACSIN2’s role in acute lymphoblastic leukemia remains sparse. Currently, there are no dedicated functional assays, expression studies, or animal models that specifically interrogate PACSIN2. The available data only imply a potential influence in drug metabolism through inclusion in broad genetic panels without targeted mechanistic studies.
Overall, the combined evidence from candidate gene association studies does not robustly support PACSIN2 as a key determinant in the pathogenesis or drug intolerance profile of acute lymphoblastic leukemia. Additional work including focused functional assessments and variant segregation analyses would be required to establish a more definitive association.
Key take‑home sentence: While PACSIN2 is a plausible candidate from initial screenings, its role in acute lymphoblastic leukemia remains limited and should be interpreted with caution in clinical diagnostic decision‑making.
Gene–Disease AssociationLimitedCandidate gene panels in pediatric ALL maintenance therapy, incorporating data from 2 multi‐patient studies (PMID:29683944, PMID:32221476), revealed inconsistent associations without segregation or robust statistical support for PACSIN2. Genetic EvidenceLimitedAlthough PACSIN2 was screened alongside other candidate genes, its variants did not significantly correlate with mercaptopurine/methotrexate intolerance, and no clear variant-level evidence was provided. Functional EvidenceLimitedNo dedicated functional experiments, animal models, or expression studies have been performed to elucidate the mechanistic role of PACSIN2 in acute lymphoblastic leukemia, leaving the functional evidence insufficient. |