Functional characterization of the 9q34.13 locus identifies <i>RAPGEF1</i> as modulating risk for melanoma and nevi via RAS activation.

ABSTRACT: Genome-wide association studies identified a melanoma- and nevus count-associated locus on chromosome band 9q34.13. Fine-mapping and melanocyte expression data collectively suggest two potential causal genes with opposite association with risk: higher levels of Rap guanine nucleotide exchange factor 1 (RAPGEF1) and lower levels of uridine-cytidine kinase 1 (UCK1). Colocalization analyses and conditional TWAS suggest multiple causal cis-regulatory sequence variants in partial linkage disequilibrium (LD) to each other. Melanocyte capture-HiC and CRISPR-inhibition demonstrated regulatory interactions between fine-mapped variants and the RAPGEF1 and UCK1 promoters. Focusing on RAPGEF1, we demonstrate RAPGEF1 expression promotes melanocyte growth

SUBMITTER: Thakur R 

PROVIDER: S-EPMC13151941 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature