This gene encodes the sacsin protein, which includes a UbL domain at the N-terminus, a DnaJ domain, and a HEPN domain at the C-terminus. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. This gene includes a very large exon spanning more than 12.8 kb. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. The authors of a publication on the effects of siRNA-mediated sacsin knockdown concluded that sacsin protects against mutant ataxin-1 and suggest that "the large multi-domain sacsin protein is able to recruit Hsp70 chaperone action and has the potential to regulate the effects of other ataxia proteins" (Parfitt et al., PubMed: 19208651). A pseudogene associated with this gene is located on chromosome 11. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
Transcription factors with Perturb-seq knockdown data for SACS. 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 = SACS 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 SACS, 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 |
|---|---|---|---|---|
| chr13:21,669,106–21,671,240 | 1762.7 kb | Distal (>10kb) Multiome HiCAR | 657 | |
| chr13:21,673,391–21,674,552 | 1759.8 kb | Distal (>10kb) Multiome HiCAR | 365 | |
| chr13:23,374,960–23,376,063 | 58.1 kb | Distal (>10kb) Multiome | 599 | |
| chr13:23,433,146–23,433,790 | 256 bp | At TSS Multiome | 270 | |
| chr13:23,466,173–23,466,976 | 32.9 kb | Distal (>10kb) Multiome | 601 | |
| chr13:23,515,532–23,516,749 | 82.6 kb | Distal (>10kb) Multiome | 118 | |
| chr13:23,578,554–23,580,035 | 145.6 kb | Distal (>10kb) Multiome | 775 | |
| chr13:23,599,048–23,599,905 | 165.9 kb | Distal (>10kb) Multiome | 286 | |
| chr13:23,630,212–23,631,077 | 196.9 kb | Distal (>10kb) Multiome | 302 | |
| chr13:23,888,469–23,890,045 | 455.7 kb | Distal (>10kb) Multiome HiCAR | 802 |
Genomic view of the SACS 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.