RIT1 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, ClinVar

RIT1 (Ras-like without CAAX 1) is a member of the RAS subfamily of small GTPases. Unlike classical RAS proteins, RIT1 lacks the C-terminal CAAX motif required for membrane localization and is predominantly cytosolic. It functions as a molecular switch in signal transduction pathways, regulating cell proliferation, differentiation, and survival. Gain-of-function mutations in RIT1 are associated with Noonan syndrome and various cancers, particularly lung adenocarcinoma.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• MAPK signaling pathway (KEGG: hsa04010)

• RAS signaling pathway (KEGG: hsa04014)

• Signaling by RAS mutants (Reactome: R-HSA-9649948)

RIT1 is a 219-amino-acid small GTPase belonging to the RAS superfamily. It shares structural homology with classical RAS proteins but lacks a CAAX motif, resulting in cytosolic localization. RIT1 cycles between an active GTP-bound state and an inactive GDP-bound state, regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Active RIT1 engages downstream effectors such as RAF kinases, leading to MAPK pathway activation. Mutations that impair GTP hydrolysis or enhance nucleotide exchange cause constitutive signaling, underlying Noonan syndrome and oncogenesis.