This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript is produced from an overlapping locus on the opposite strand. One of the transcripts produced from this locus, and the antisense transcript, are paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein - Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene result in pseudohypoparathyroidism type 1a, pseudohypoparathyroidism type 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors. [provided by RefSeq, Aug 2012]
Transcription factors with Perturb-seq knockdown data for GNAS. 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 = GNAS 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 GNAS, 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 |
|---|---|---|---|---|
| chr20:58,546,673–58,547,327 | 294.6 kb | Distal (>10kb) Multiome | 69 | |
| chr20:58,649,950–58,652,788 | 190.5 kb | Distal (>10kb) Multiome | 1208 | |
| chr20:58,669,288–58,669,967 | 172.0 kb | Distal (>10kb) Multiome | 158 | |
| chr20:58,692,413–58,693,477 | 148.9 kb | Distal (>10kb) Multiome | 317 | |
| chr20:58,850,471–58,851,960 | 9.3 kb | Proximal (<10kb) Multiome | 308 | |
| chr20:58,852,406–58,852,990 | 11.2 kb | Distal (>10kb) Multiome | 172 | |
| chr20:58,888,196–58,892,842 | 47.4 kb | Distal (>10kb) Multiome | 977 | |
| chr20:58,980,774–58,981,785 | 139.6 kb | Distal (>10kb) Multiome | 797 | |
| chr20:59,006,785–59,007,608 | 165.6 kb | Distal (>10kb) Multiome | 401 | |
| chr20:59,031,825–59,033,029 | 190.8 kb | Distal (>10kb) Multiome | 1108 | |
| chr20:59,042,196–59,043,527 | 201.2 kb | Distal (>10kb) Multiome | 834 | |
| chr20:59,222,192–59,223,002 | 381.0 kb | Distal (>10kb) Multiome HiCAR | 395 |
Genomic view of the GNAS 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.