protein C9orf72 (C9orf72)
Jump to navigation
Jump to search
Compartment
- cytoplasm. nucleus
- detected in the cytoplasm of neurons from post mortem brain tissue[2]
- detected in the nucleus in fibroblasts[3]
Alternative splicing
- named isoforms=2
- encoded by 2 transcripts differing in the 5' non-coding region
Expression
- both isoforms are widely expressed, including kidney, lung, liver, heart, testis & several brain regions
- in brain, expressed in cerebellum, frontal cortex
- expressed in lymphoblasts (at protein level)
Pathology
- defects in the gene associated with:
- GGGGCC hexanucleotide expansion within the first C9orf72 intron
- the expansion leads to the loss of transcription of one of the two transcripts encoding isoform 1 & to the formation of nuclear RNA foci
- production of large amounts of sense & anti-sense mRNA[4]
Pharmacology
- repeated intrathecal antisense oligonucleotides that selectively blunt expression of G4C2 repeat-containing transcripts & effectively suppress CSF levels of poly(Gly-Pro) dipeptides[5]
Notes
uncertain whether Met-1 or Met-7 is the initiator
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q96LT6.html
- ↑ 2.0 2.1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21944778
- ↑ 3.0 3.1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21944779
- ↑ 4.0 4.1 Mizielinska S, Lashley T, Norona FE et al C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci. Acta Neuropathol. 2013 Oct 30. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/24170096
- ↑ 5.0 5.1 Tran H, Moazami MP, Yang H et al Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide. Nature Medicine 2021. Dec 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34949835 https://www.nature.com/articles/s41591-021-01557-6
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=203228
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:203228
- OMIM: https://mirror.omim.org/entry/105550
- OMIM: https://mirror.omim.org/entry/614260
- UniProt: http://www.uniprot.org/uniprot/Q96LT7.html