Three different human RAS genes have been identified: KRAS (homologous to the oncogene from the Kirsten rat sarcoma virus), HRAS (homologous to the oncogene from the Harvey rat sarcoma virus), and NRAS (first isolated from a human neuroblastoma). The different RAS genes are highly homologous but functionally distinct; the degree of redundancy remains a topic of investigation (reviewed in Pylayeva-Gupta et al. 2011). RAS proteins are small GTPases that cycle between inactive guanosine diphosphate–bound and active guanosine triphosphate–bound forms. RAS proteins are central mediators downstream of growth factor receptor signaling and therefore are critical for cell proliferation, survival, and differentiation. RAS proteins can activate several downstream effectors, including the PI3K-AKT-mTOR pathway, which is involved in cell survival, and the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation (Figure 1).

Specific RAS genes are recurrently mutated in different malignancies. HRAS mutations are particularly common in salivary gland, urinary tract, upper aerodigestive tract, cervical, and thyroid (for reviews see Karnoub and Weinberg 2008 and Schubbert, Shannon, and Bollag 2007).


Figure 1. Simplified schematic of RAS signaling pathways. Growth factor binding to receptor tyrosine kinases results in RAS activation. The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Allan V. Espinosa, M.D., Jill Gilbert, M.D., James Fagin, M.D.

Suggested Citation: Espinosa, A.V., Gilbert, J., Fagin, J. 2015. HRAS. My Cancer Genome (Updated December 2015)

Modified: December 7, 2015

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