RTN4 Gene: Reticulon 4 - Function, Mutations, and Disease Associations

The RTN4 gene encodes reticulon 4, a member of the reticulon family of proteins. It is primarily known as Nogo, a potent inhibitor of neurite outgrowth in the central nervous system. RTN4 is involved in apoptosis, cell cycle regulation, and vascular remodeling. Alternative splicing generates multiple isoforms, including Nogo-A, Nogo-B, and Nogo-C, which have distinct tissue distributions and functions. RTN4 is implicated in multiple sclerosis, amyotrophic lateral sclerosis, and various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• R-HSA-193648 - Nogo receptor signaling

• R-HSA-194315 - Signaling by Rho GTPases

• R-HSA-204998 - Cell death signaling via NRAGE

• NRIF

• NADE

• R-HSA-2219530 - Reticulon-mediated ER shaping

Reticulon 4 (RTN4) is a 1192-amino acid protein with a conserved reticulon domain that induces ER membrane curvature. It has three major isoforms: Nogo-A (longest, predominantly in CNS), Nogo-B (ubiquitous), and Nogo-C (short, in muscle and testis). Nogo-A contains a 66-amino acid extracellular loop (Nogo-66) that binds the Nogo receptor (NgR1) to inhibit neurite outgrowth. RTN4 also interacts with Bcl-2 family proteins to regulate apoptosis. In cancer, RTN4 promotes cell migration and invasion through PI3K/Akt signaling.