The GIT1 gene encodes an enzyme that functions as a GTPase activating protein for the ADP ribosylation factor (Arf) family. By carrying out its function, it is responsible for the increased phosphorylation and reduced signaling of the beta-2-adrenergic receptor (ADBR2). The protein has also been speculated to play a role in the increased speed of cell migration, the size and frequency of membrane protrusions and in the regulation of cytokinesis.
Animal studies have helped further elucidate the role of this protein. Git1 knockout mice have been shown to exhibit ADHD-like behavior, such as hyperactivity, impairment of memory and learning ability and enhanced theta rhythms. Recent studies have also identified GIT1 as an enhancer of huntingtin aggregation, thus potentially implicating it in Huntington disease.
The GIT1 gene, located on the long arm of chromosome 17, spans a length of 20.5 kb of DNA. Its coding sequence is contained within 21 exons and the gene encodes an 84 kDa protein product comprised of 761 amino acids. Several additional isoforms of the GIT1 gene exist due to alternatively spliced transcript variants. While the gene is widely expressed in the human body, overexpression is seen in the brain and peripheral blood mononuclear cells.
Monies et al. (2017) reported the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One 4-year-old male patient suffered from dystonia. Using whole exome sequencing, a heterozygous mutation (c.611T>A, p.I204N) was identified in exon 5 of the patient’s GIT1 gene. This mutation was considered a candidate for pathogenicity as it was a novel variant predicted to be deleterious, and Git1 knockout mice displayed a compatible phenotype. The authors noted that further studies were required to independently confirm this association.
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