RTN4R Gene: Reticulon 4 Receptor – Function, Mutations, and Clinical Significance

RTN4R encodes the reticulon 4 receptor (NgR1), a glycosylphosphatidylinositol (GPI)-anchored protein that binds myelin-associated inhibitors (MAIs) such as Nogo-A, MAG, and OMgp. This receptor complex mediates inhibition of axonal growth and neural regeneration in the central nervous system (CNS). RTN4R is also implicated in synaptic plasticity, neuronal survival, and immune modulation. Genetic variants in RTN4R have been associated with schizophrenia, multiple sclerosis, and altered recovery after spinal cord injury.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• R-HSA-193648 – Nogo-66 receptor (NgR1) signaling

• R-HSA-193697 – Signaling by NGF

• R-HSA-422475 – Axon guidance

• R-HSA-6794361 – Neurexins and neuroligins

• WP286 – Spinal cord injury

The reticulon 4 receptor (NgR1) is a 473-amino acid GPI-anchored protein with a signal peptide, eight leucine-rich repeats (LRRs), a cysteine-rich domain, and a C-terminal GPI attachment site. It forms a signaling complex with p75NTR, LINGO-1, and TROY to activate RhoA, leading to growth cone collapse and inhibition of neurite outgrowth. NgR1 is predominantly expressed in neurons of the CNS, especially in brain, spinal cord, and retina. Alternative splicing generates isoforms with varying ligand-binding affinities. Post-translational modifications include glycosylation and GPI anchor addition.