SH3GLB1

The protein regulates mitochondrial membrane dynamics, autophagy, and apoptotic signaling pathways, and is involved in membrane trafficking and cytokinesis. Mutations cause autosomal recessive spastic paraplegia with childhood onset, characterized by progressive spasticity primarily affecting the lower limbs and intellectual disability. The gene shows significant constraint against loss-of-function variants, suggesting that complete loss of protein function is not well tolerated.