The GAP43 gene encodes a cytoplasmic protein specifically found in nervous tissue. The GAP43 protein can be connected to the synaptosomal membrane via a dual palmitoylation sequence that targets lipid rafts. While the protein is yet to be fully characterized, studies on lower orthologs and mouse knockout models have helped elucidate its physiological role. It is found to be highly expressed in ‘neuronal growth cones’, located on the tips of elongating axons and dendrites, particularly during development and axonal regeneration. The protein is hence believed to play a role in the growth and plasticity of axons in the central nervous system.
The GAP43 gene is located on the long arm of chromosome 3. It spans a length of 98 kb of DNA and its coding sequence is spread across 4 exons. The gene encodes a 24.8 kDa protein product comprised of 238 amino acids. An additional 28.7 kDa isoform of the GAP43 protein exists due to an alternatively spliced transcript variant. The gene is overexpressed in the fetal and adult brain, as well as in the retina and adrenal gland.
Monies et al. (2017) illustrated the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 32-year-old female, presented with motor neuron disease and paraparesis. She was spastic with upper and lower motor neuron signs. Using whole exome sequencing, a heterozygous mutation (c.629-3C>T) was identified in exon 3 of the patient’s GAP43 gene. This gene mutation was considered a candidate for pathogenicity as it was a novel variant that was predicted to be deleterious; and the gene had been reported to be involved in axon regeneration. The authors noted that further studies were required to independently confirm this association.
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