GNAS
GNAS complex locus | GNASXL, GPSA, NESP, NESP55, SCG6, SgVI, GNAS1

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]

Member of: DE-1 DE-1.19 Developmental clusters: GC2
Biological processes 87 terms
D1 dopamine receptor binding (GO:0031748)D1 dopamine receptor binding (GO:0031748)G protein activity (GO:0003925)G protein activity (GO:0003925)G protein-coupled receptor signaling pathway (GO:0007186)G protein-coupled receptor signaling pathway (GO:0007186)G-protein beta/gamma-subunit complex binding (GO:0031683)G-protein beta/gamma-subunit complex binding (GO:0031683)GTP binding (GO:0005525)GTPase activity (GO:0003924)GTPase activity (GO:0003924)GTPase activity (GO:0003924)activation of adenylate cyclase activity (GO:0007190)adenylate cyclase activator activity (GO:0010856)adenylate cyclase activator activity (GO:0010856)adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway (GO:0038184)adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189)adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189)adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880)adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191)adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191)adenylate cyclase-activating serotonin receptor signaling pathway (GO:0007192)apical plasma membrane (GO:0016324)beta-2 adrenergic receptor binding (GO:0031698)bone development (GO:0060348)bone development (GO:0060348)cellular response to acidic pH (GO:0071468)cellular response to catecholamine stimulus (GO:0071870)cellular response to glucagon stimulus (GO:0071377)cellular response to prostaglandin E stimulus (GO:0071380)cognition (GO:0050890)cognition (GO:0050890)corticotropin-releasing hormone receptor 1 binding (GO:0051430)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasmic side of plasma membrane (GO:0009898)cytosol (GO:0005829)cytosol (GO:0005829)developmental growth (GO:0048589)developmental growth (GO:0048589)extracellular exosome (GO:0070062)extracellular region (GO:0005576)female pregnancy (GO:0007565)guanyl nucleotide binding (GO:0019001)hair follicle placode formation (GO:0060789)hair follicle placode formation (GO:0060789)heterotrimeric G-protein complex (GO:0005834)heterotrimeric G-protein complex (GO:0005834)heterotrimeric G-protein complex (GO:0005834)insulin-like growth factor receptor binding (GO:0005159)intracellular glucose homeostasis (GO:0001678)intracellular transport (GO:0046907)ionotropic glutamate receptor binding (GO:0035255)membrane (GO:0016020)membrane (GO:0016020)membrane (GO:0016020)mu-type opioid receptor binding (GO:0031852)negative regulation of inflammatory response to antigenic stimulus (GO:0002862)negative regulation of multicellular organism growth (GO:0040015)nucleus (GO:0005634)perinuclear region of cytoplasm (GO:0048471)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)platelet aggregation (GO:0070527)platelet aggregation (GO:0070527)positive regulation of cold-induced thermogenesis (GO:0120162)positive regulation of insulin secretion (GO:0032024)positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774)protein binding (GO:0005515)protein secretion (GO:0009306)regulation of signal transduction (GO:0009966)regulation of skeletal muscle contraction (GO:0014819)renal water homeostasis (GO:0003091)response to parathyroid hormone (GO:0071107)response to parathyroid hormone (GO:0071107)response to prostaglandin E (GO:0034695)ruffle (GO:0001726)sensory perception of chemical stimulus (GO:0007606)sensory perception of smell (GO:0007608)signal transduction (GO:0007165)trans-Golgi network membrane (GO:0032588)transport vesicle (GO:0030133)vascular endothelial cell response to laminar fluid shear stress (GO:0097700)
Expression (TPM)
GNAS — as a Regulated Gene

TFs regulating GNAS 0 TFs

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.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to GNAS

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

Genome Browser

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.

chr20:58,536,673 – 59,233,002
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq