The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]
Transcription factors with Perturb-seq knockdown data for C9orf72. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = C9orf72 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of C9orf72, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr9:27,353,413–27,354,230 | 220.0 kb | Distal (>10kb) Multiome | 252 | |
| chr9:27,369,370–27,370,284 | 204.0 kb | Distal (>10kb) Multiome | 166 | |
| chr9:27,527,691–27,530,287 | 45.5 kb | Distal (>10kb) Multiome | 646 | |
| chr9:27,572,547–27,574,260 | 189 bp | At TSS Multiome | 778 | |
| chr9:27,749,616–27,750,339 | 176.1 kb | Distal (>10kb) Multiome | 209 | |
| chr9:27,771,599–27,772,601 | 198.2 kb | Distal (>10kb) Multiome | 306 |
Genomic view of the C9orf72 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.