RTN2

The RTN2 protein localizes to the endoplasmic reticulum where it inhibits amyloid precursor protein processing and enhances trafficking of transporters including glutamate and glucose transporters to the cell surface. Mutations cause either autosomal dominant spastic paraplegia-12 or autosomal recessive distal hereditary motor neuronopathy with spasticity, both affecting motor neurons and causing progressive spasticity. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.417), and the differing inheritance patterns suggest distinct pathogenic mechanisms for different mutation types.