HRAS is a membrane-associated GTPase that acts as a molecular switch in cell signaling, cycling between active and inactive states as it binds and hydrolyzes GTP. It belongs to the RAS family of proto-oncogenes and helps transmit growth and survival signals through pathways such as MAPK and PI3K. Germline mutations in HRAS cause Costello syndrome, a developmental disorder marked by distinctive facial features, growth and cognitive problems, and a predisposition to tumors. Somatic HRAS mutations also drive many cancers, including cancers of the thyroid, bladder, and salivary glands.

Germline HRAS mutations cause Costello syndrome and somatic mutations drive cancers of the thyroid, bladder, and salivary glands, so a missense change in HRAS is potentially relevant to disease. This variant, p.(Glu3Lys), is absent from population databases but has no reported pathogenic, functional, or clinical evidence, so it cannot yet be assigned pathogenic or benign significance and remains a variant of uncertain significance pending further observations.