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Hepatic veno‑occlusive disease (also known as sinusoidal obstruction syndrome, SOS) is a severe complication observed in patients undergoing hematopoietic stem cell transplantation. Recent genetic investigations have sought to elucidate risk factors contributing to SOS, and LNPK (HGNC:21610) has emerged as a candidate gene from exome‑wide analyses. In a discovery cohort of 87 pediatric patients undergoing HSCT (PMID:31790828), LNPK was included among several genes of interest. Although the aggregate study design evaluated multiple genetic loci, LNPK’s role was noted as part of a broader assessment of genetic susceptibility. This summary integrates data from multi‑patient studies and sets the stage for an improved understanding of its clinical relevance. The current evidence provides a preliminary framework for considering LNPK in the risk stratification of SOS.
In the primary study, an exome‑wide association approach was applied to a carefully characterized cohort of HSCT patients. The study included a discovery phase with 87 patients and a subsequent validation phase with 182 patients (PMID:31790828). Although detailed variant‐level data for LNPK was not explicitly provided in the abstract, its inclusion in the gene panel underscores its potential involvement. Additional case information regarding segregation or familial occurrence was not available, which limits a more comprehensive genetic evaluation. Nonetheless, the identification of LNPK as a candidate gene supports the premise of a genetic contribution to SOS.
A systematic review further examined the genetic underpinnings of SOS by evaluating data from 23 studies post‑HSCT (PMID:33925809). In this review, variants in LNPK were detected through whole‑exome sequencing analyses, lending some support to its association with SOS. While the review highlighted other genes with more extensive evidence, the recurring detection of LNPK across studies suggests that it may contribute to the genetic heterogeneity of the disease. However, the lack of clear segregation data and detailed variant description specifically for LNPK confines the level of evidence to a preliminary stage.
The genetic evidence from the available studies indicates a candidate association between LNPK and hepatic veno‑occlusive disease. Although a definitive causative variant has not been reported for LNPK, its repeated identification in unbiased exome‑wide studies implies that it may act as a risk modifier. The absence of recurrent, well‐characterized LNPK variants or familial segregation data limits the strength of the genetic association at present. This limitation underscores the need for additional studies that can further clarify the contribution of LNPK variants to the disease phenotype.
In contrast, experimental and functional studies specifically addressing LNPK’s role in the pathogenesis of SOS are currently lacking. There are no targeted functional assays, cellular expression studies, or animal model investigations that directly link LNPK dysfunction to hepatic endothelial injury or hepatocellular damage. Consequently, functional evidence remains limited and does not yet provide mechanistic insights into how LNPK might contribute to disease development. Future targeted studies will be critical to establish the biological plausibility of LNPK’s involvement in SOS.
In conclusion, the association between LNPK (HGNC:21610) and hepatic veno‑occlusive disease (MONDO_0019514) is supported by limited genetic evidence derived from exome‑wide studies and systematic reviews. While the repeated identification of LNPK in independent cohorts suggests a potential role in disease susceptibility, the absence of detailed variant, segregation, and functional analyses restricts the association to a candidate level. Further investigations are warranted to validate LNPK as a clinically actionable marker. Key take‑home sentence: Although current evidence is limited, LNPK remains a promising candidate for inclusion in future genetic risk assessments of hepatic veno‑occlusive disease.
Gene–Disease AssociationLimitedCandidate association identified through an exome‑wide study in a discovery cohort of 87 patients (PMID:31790828) and further discussed in a systematic review (PMID:33925809); however, detailed segregation and variant-level evidence are lacking. Genetic EvidenceLimitedLNPK was detected in whole‑exome sequencing analyses without reporting recurrent or well‐characterized variants, and familial segregation data is not provided. Functional EvidenceLimitedNo targeted functional assays, animal models, or expression studies have been reported to elucidate LNPK’s mechanistic role in hepatic veno‑occlusive disease. |