WARS2 is the abbreviated gene name for the tryptophanyl tRNA synthetase (W = amino acid tryptophan; A = aminoacyl; R = tRNA; S = synthetase; 2 = second gene identified). The gene resides in the nucleus and the transcribed protein is translocated to the mitochondria. Its location in the genome is at 1p12, on chromosome 1. There are six exons that compose the gene.
The following is a layman's explanation: The mitochondria are located in every cell of the body and generate most energy needed by each cell. When the mitochondria are unable to provide energy, the cell will generate energy by another mechanism that is most recognizable by the burning feeling in muscles during strenuous activity. The mitochondria have their own DNA that is seperate from the remaining cell and needed to make proteins for the functioning of the mitochondria. In order to make these proteins, the mitochondria needs to create the building blocks, which involves WARS2. WARS2 will attach the amino acid tryptophan to a tRNA, which is used as a building block. An insufficient supply of this building block would have a negative impact on the ability of the mitochondria to produce energy.
The condition is autosomal recessive, requiring both copies to have a mutation. An individual with a single unaffected copy will appear normal without symptoms. Interestingly, there are six individuals with two copies each of the W13G mutation who were normal between the ages of 40 and 65 when their DNA was sequenced and submitted to the gnomAD database. Mutation W13G likely decreases the total amount of WARS2 making it to the mitochondria, and there may be a minimum amount needed for normal function that allows two W13G mutants or one unaffected copy of the gene to show no visible symptoms. The syndrome has been referred to as early-onset Parkinsonism and "neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS)". The WARS2 patients have a diverse range of severity of symptoms that is likely due to the specific location of the mutation in the gene and specific combination of mutations.
As seen in the figure below (from the GTEx portal), WARS2 is expressed throughout the whole body without any noticeable outliers with similar levels throughout the brain.
More information will be provided at a later time.