Genetic variation at the MECOM locus shaping human disease pathogenesis

The gene MDS1 and EVI1 complex locus (MECOM) functions as a transcriptional regulator essential for development. Variants in MECOM have been recognized as pathogenic drivers, with well-established links to oncologic and hematopoietic disorders and increasing evidence for roles in cardiovascular diseases. Here, we examine the spectrum of MECOM variants and their connections to human diseases by integrating findings from genome-wide association studies (GWAS), expression quantitative trait loci (eQTL) analyses, and curated databases, together with single-case reports from whole-exome (WES) and whole-genome sequencing (WGS). Combining insights from both common and rare variants, we provide a comprehensive review of MECOM's genetic landscape and outline how specific alterations contribute to pathogenic mechanisms. We also highlight strategies targeting MECOM and the urgent need to investigate MECOM-associated single-nucleotide polymorphisms (SNPs) as both mechanistic drivers and potential therapeutic targets.