Homozygous loss of function mutations in SLC1A1cause dicarboxylic aminoaciduria (or glutamate-aspartate transport defect), which is characterized by excessive urinary loss of aspartate and glutamate resulting from the incomplete reabsorption of dicarboxylic amino acids from the glomerular filtrate. Dicarboxylic aminoaciduria can be associated with kidney stones and may be associated with neuropsychiatric manifestations, potentially including developmental disability, psychosis, or obsessive-compulsive symptoms. It has an estimated prevalence of 1 in 35,000 births.
A homozygous loss of function mutation (p.E48X) was described in a 2019 study by Doan and colleagues in an autistic individual from Germany. A heterozygous deletion encompassing the promotor region and exon 1 of SLC1A1was identified in individuals with psychosis in a 5-generation Palauan family, with the mutation proposed to increase the disease risk more than 18-fold for family members. Association of SLC1A1single nucleotide polymorphisms (SNPs) that change gene expression have been reported in schizophrenia and in obsessive compulsive disorder (OCD), but genome-wide association studies have not identified significant association with SLC1A1in schizophrenia or OCD to date.
SLC1A1