This gene encodes a member of the voltage-gated chloride channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
Transcription factors with Perturb-seq knockdown data for CLCN3. 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 = CLCN3 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 CLCN3, 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 |
|---|---|---|---|---|
| chr4:169,334,284–169,334,914 | 286.0 kb | Distal (>10kb) Multiome | 96 | |
| chr4:169,347,007–169,347,496 | 273.3 kb | Distal (>10kb) Multiome | 18 | |
| chr4:169,611,998–169,613,442 | 7.9 kb | Proximal (<10kb) Multiome | 840 | |
| chr4:169,619,326–169,619,817 | 710 bp | At TSS | 291 | |
| chr4:169,619,912–169,621,246 | 75 bp | At TSS Multiome | 896 | |
| chr4:169,659,977–169,660,707 | at TSS | At TSS | 628 | |
| chr4:169,757,346–169,758,297 | 137.4 kb | Distal (>10kb) Multiome | 724 | |
| chr4:169,774,514–169,775,438 | 154.5 kb | Distal (>10kb) Multiome | 195 | |
| chr4:169,918,815–169,920,220 | 299.3 kb | Distal (>10kb) Multiome | 227 | |
| chr4:169,934,787–169,935,471 | 314.5 kb | Distal (>10kb) Multiome | 121 | |
| chr4:170,025,638–170,027,809 | 405.9 kb | Distal (>10kb) Multiome HiCAR | 968 |
Genomic view of the CLCN3 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.