Functional characterization of the 9q34.13 locus identifies RAPGEF1 as a candidate gene modulating risk for melanoma and nevi via RAS activation.

Higher RAPGEF1 levels are linked to increased melanoma and nevus risk by activating RAS signaling pathways in melanocytes.

• Why it matters: Understanding genetic factors that influence melanoma risk is crucial for early detection and targeted therapies, especially since RAS pathway activation is a key driver in melanoma development.
• What they did: The study used fine-mapping, expression data, chromatin interaction analyses, and CRISPR inhibition to identify regulatory variants affecting RAPGEF1 and UCK1, focusing on RAPGEF1's role in melanocyte growth and RAS activation.
• The result: Elevated RAPGEF1 promotes melanocyte proliferation and RAS pathway activation, especially in melanomas lacking RAS or BRAF mutations, highlighting its potential as a prognostic marker and therapeutic target.