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Description

Guanine nucleotide exchange C9orf72 (UniProt: Q96LT7, also known as C9orf72) is encoded by the C9orf72 gene (Gene ID: 203228) in human. C9orf72 generates three transcripts through alternative splicing that encode 2 protein isoforms: a long isoform of about 54 kDa (termed C9-L), corresponding to variants 2 and 3, and a short isoform of about 24 kDa (termed C9-S) corresponding to variant 1. Both isoforms are widely expressed, including in kidney, lung, liver, heart, testis, and several brain regions. The long isoform of 481 amino acids is shown to be the predominant form that is expressed in human brain. Expansion of a GGGGCC (G4C2) hexanucleotide repeat sequence in the non-coding region of human C9orf72 is the most common genetic abnormality in familial and sporadic frontotemporal dementia (FTD) and motor neuron disease (MND), with amyotrophic lateral sclerosis (ALS) as the most frequent form. Both, C9-L and C9-S are reported to display distinct subcellular localizations in cerebellar Purkinje cells of both c9-ALS and non c9-ALS cases. C9-L is shown to be spread diffusely throughout the cytoplasm, whereas C9- S is localized to the nuclear membrane of Purkinje cells of both c9-ALS and non-c9-ALS cases. Also, C9-L is shown to be present mainly in the high-salt Triton and urea-soluble fractions, whereas C9-S is shown to be abundant in both the low- and high-salt Triton fractions, indicating differences in their subcellular localizations. (Ref.: Frick, P., et al. (2018). Acta Neuropathol. Commun. 6(1), 72).