Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]
Transcription factors with Perturb-seq knockdown data for DENND1A. 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 = DENND1A 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 DENND1A, 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 |
|---|---|---|---|---|
| chr9:123,655,350–123,656,332 | 274.2 kb | Distal (>10kb) Multiome | 169 | |
| chr9:123,929,360–123,930,900 | 35 bp | At TSS Multiome | 689 | |
| chr9:124,008,456–124,009,293 | 78.7 kb | Distal (>10kb) Multiome | 302 | |
| chr9:124,010,900–124,012,625 | 81.4 kb | Distal (>10kb) Multiome | 465 | |
| chr9:124,040,710–124,041,459 | 111.0 kb | Distal (>10kb) Multiome | 331 |
Genomic view of the DENND1A 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.