Chromosome 9 open reading frame 72 protein (C9orf72)

Chromosome 9 open reading frame 72 protein (*C9orf72*) is encoded by the *C9orf72* gene located at cytogenetic band 9p21.2 on human chromosome 9. The protein plays an important role in regulating endosomal trafficking, lysosome homeostasis, autophagy, and nutrient-dependent mTORC1 signaling through interactions with SMCR8 and WDR41 proteins—forming a functional complex critical for neuronal health. Pathogenic hexanucleotide GGGGCC repeat expansions within an intronic region cause both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), making it one of the most common genetic causes identified for these neurodegenerative disorders. Disease mechanisms involve both gain-of-function toxicity from abnormal RNA/protein products generated from expanded repeats as well as loss-of-function effects due to reduced levels or dysfunction of normal C9ORF72 protein.

Other names

C9orf72C9ORF72-SMCR8 complex subunitALSFTDFTDALSchromosome Z C9orf72 homolog (CZH9orf72)RIKEN cDNA 3110043O21 gene (3110043O21Rik)similar to RIKEN cDNA 3110043O21 (RGD1359108)chromosome 9 open reading frame 72 L homeolog (c9orf72.L)

Experimental therapeutics aim to reduce toxic RNA foci or dipeptide repeat proteins produced by pathogenic hexanucleotide repeat expansions within the *C9orf72* gene. Approaches include antisense oligonucleotides that bind mutant RNA transcripts for degradation or prevent their translation into toxic peptides; other strategies may involve modulating autophagy pathways affected by loss-of-function mutations in C9orf72.