Defective SLC33A1 causes spastic paraplegia 42 (SPG42)

The human gene SLC33A1 encodes acetyl-CoA transporter AT1. SLC33A1 transports cytosolic acetyl-CoA (Ac-CoA) to the Golgi apparatus lumen, where it serves as the substrate for acetyltransferases that O-acetylates sialyl residues of gangliosides and glycoproteins. Defects in SLC33A1 are the cause of spastic paraplegia autosomal dominant type 42 (SPG42; MIM:612539), a neurodegenerative disorder characterised by a variable speed of (but progressive) weakness and spasticity of the lower limbs. Defects in SLC33A1 can also cause congenital cataracts, hearing loss, and neurodegeneration (CCHLND; MIM:614482), an autosomal recessive disorder characterised by congenital cataracts, severe psychomotor retardation, and hearing loss, together with decreased serum ceruloplasmin and copper.

Summary from Reactome (R-HSA-5619061), read 2026-09-23.