Identity

HGNC
LOCATION
20q13.32
IMAGE
Atlas Image
LEGEND
Figure 1. Organization and imprinting of the GNAS complex locus. The general organization and imprinting patterns of the paternal (above) and maternal (below) GNAS alleles are shown, with the exons of sense transcripts (NESP55, XL, A/B, and Gαs) depicted as black boxes, the common exons 2 to 13 represented as green boxes, the five exons of the antisense transcript (AS) represented as grey boxes and the eight exons of the STX16 gene represented as orange boxes. The active sense and antisense promoters (arrows), as well as the splicing patterns of their respective paternal (blue) and maternal (pink) transcripts, are shown above and below the paternal and maternal exons, respectively. The dotted arrow for the paternal Gαs transcription indicates that the promoter is fully active in most tissues but is presumed to be silenced in some tissues, such as renal proximal tubules. Regions that are differentially methylated are represented as stars (red, methylated and white, unmethylated).
LOCUSID
ALIAS
AHO,C20orf45,GNAS1,GPSA,GSA,GSP,NESP,PITA3,POH,SCG6,SgVI
FUSION GENES

DNA/RNA

Atlas Image
Figure 2. Gsα protein isoforms. Two long (Gsα-1 and Gsα-2) and two short (Gsα-3 and Gsα-4) forms of Gsα result from alternative splicing of exon 3. Use of an alternative splice acceptor site for exon 4 leads to insertion of an extra serine residue in Gsα-2 and Gsα-4. Introns are represented as dash lines, exons as orange boxes; UTRs as black boxes, serine residue as blue hexagons and splicing pattern as a solid line

Description

The GNAS gene spans over 20-kilobase pair and contains thirteen exons and codifies the α-subunit of the stimulatory G protein (Gsα) (Kozasa et al., 1988).

Transcription

The GNAS locus produces multiple gene products as it has four alternative first exons (NESP55 (Ischia et al., 1997), XLαs (Kehlenbach et al., 1994), A/B (Ishikawa et al., 1990; Swaroop et al., 1991) and E1-Gsα) that splice onto a common exons 2 to 13. These first alternative exons lie within CpG islands and are differently imprinted, while to increase its complexity this locus also has an antisense transcript to NESP55, referred as NESPas (Hayward and Bonthron, 2000) (Figure 1).
Exon A/B or exon 1A, located 2.5 kb centromeric from Gsα exon 1, splices onto common exons 2-13, and is methylated on the maternal allele. In this case, because there is no consensus AUG translational start site in exon A/B, it is thought that the resulting transcript is not translated (Ishikawa et al., 1990; Liu et al., 2000). It has been suggested that this region has a negative regulatory cis-acting element that suppresses the paternal Gsα allele in a tissue specific manner (i.e. renal proximal tubules) (Williamson et al., 2004; Liu et al., 2005).
XLαs alternative first exon, is located about 35 kb centromeric from Gsα exon 1, join exons 2-13 leading a transcript that encodes the extra large protein (XLαs), an isoform of Gsα with similar functions but slightly longer, and its promoter is imprinted on the maternal allele (Hayward et al., 1998b).
Finally, the farthest alternative exon (49kb centromeric from exon 1), together with the other common exons 2-13, makes the transcript encoding the protein NESP55, chromogranin-like protein that is expressed mostly in neuroendocrine tissues and only from the maternal allele, due to methylation on the paternal allele (Hayward et al., 1998b).
Regarding GNAS gene transcripts, by different splicing of exon 3 and/or use of two 5splice sites of exon 4, two long (Gsα-L) and two short (Gsα-S) transcript variants are created, which contain alternatively exon 3 and/or a CAG sequence, respectively (Figure 2) (Bray et al., 1986; Robishaw et al., 1986; Kozasa et al., 1988). It is not methylated on either allele (Kozasa et al., 1988; Hayward et al., 1998a; Peters et al., 1999; Liu et al., 2005).

Pseudogene

No pseudogenes have been identified.

Proteins

Atlas Image
Figure 3. Schematic representation of GNAS gene and Gsα protein. (A) Schematic scaled representation of the 13 coding exons for GNAS gene (Black rectangles represent the exons, grey rectangles the untranslated regions, and the black line the intronic region). (B) Schematic representation of Gsα protein, where the blue rectangles represents the 4 different domains located in the protein (exons 1 and 2 encode for the GTPase activity domain; exons 4 and 5 for the adenylyl cyclase activity domain; exon 9 for the GTP dependent conformational change domain; and exons 12 and 13 for the G-protein coupled receptor interaction domain). The figure also shows the localization of the activating mutations in exon 8 (R201) and exon 9 (Q227).

Description

The Gsα protein has 394 aminoacids with a mass of about 46 kDa. Gα-subunits contain two domains: a GTPase domain that is involved in the binding and hydrolysis of GTP and a helical domain.
The α subunit guanine nucleotide pocket consists of five distinct, highly conserved stretches (G1-G5). The G1, G4 and G5 regions are important for the binding of GTP while the G2 and G3 regions determine the intrinsic GTPase activity of the α subunit. The GDP-bound form binds tightly to bg and is inactive, whereas the GTP-bound form dissociates from bg and serves as a regulator of effector proteins. The receptor molecules cause the activation of G proteins by affecting several steps of the GTP cycle, resulting in the facilitation of the exchange of GTP for GDP on the α subunit (Lania et al., 2001; Cherfils and Chabre, 2003).

Expression

GNAS is biallelically expressed in most tissues studied (Hayward et al., 1998a; Hayward et al., 1998b; Zheng et al., 2001; Mantovani et al., 2004); however, in some tissues (thyroid, renal proximal tubule, pituitary and ovaries) primarily maternal expression is observed leading to a parental-of-origin effect (Davies and Hughes, 1993; Campbell et al., 1994; Hayward et al., 2001; Weinstein, 2001; Mantovani et al., 2002; Germain-Lee et al., 2002; Liu et al., 2003) (Yu et al., 1998).

Localisation

Cytoplasmatic membrane-associated

Function

Heterotrimeric G proteins are membrane bound GTPases that are linked to seven-transmembrane domain receptors (Kleuss and Krause, 2003). Each G protein contains an alpha-, beta- and gamma-subunit and is bound to GDP in the "off" state (Olate and Allende, 1991). Ligand-receptor binding results in detachment of the G protein, switching it to an "on" state and permitting Gα activation of second messenger signalling cascades (Cabrera-Vera et al., 2003). Gsα mediates the simulation of adenylate cyclase regulated by various peptide hormones (PTH, TSH, gonadotropins, ACTH, GHRH, ADH, glucagon, calcitonin, among others) (Spiegel, 1999; Spiegel and Weinstein, 2004). Gsα-subunits contain two domains: a GTPase domain that is involved in the binding and hydrolysis of GTP and a helical domain that buries the GTP within the core of the protein (Cabrera-Vera et al., 2003).
Exon 5 is thought to codify the highly conserved domain of Gsa that interacts with adenylate cyclase, while exon 13 is responsible for the interaction with the receptor (Pennington, 1994).

Homology

There are several types of Gα proteins; Gsα, Gqα, Gi/oα and G12/13α (Riobo and Manning, 2005). Members of Gsα bind directly to adenylyl cyclase and stimulate its activity, whereas their effects on ion channel activity are restricted to selected cell types; Gi/oα are involved in adenylyl cyclase inhibition, ion channel modulation and phosphatase activation. Finally, G12/13α family is implicated in processes of determination and cell proliferation. Subunits of the Gq/11 class are putative mediators of phospholipase C activation (Landis et al., 1989; Lania et al., 2001).

Mutations

Note

Both germinal and somatic, activating and inactivating, genetic and epigenetic alterations have been described at GNAS locus associated with different entities.
Activating mutations: Mutations at Arg201 or Gln227 inhibits the GTPase activity, maintaining Gsα in its active form. The mutant Gsα protein carrying these activating mutations is termed the gsp oncogene (Landis et al., 1989).
In McCune-Albright syndrome, the somatic mutation at Arg201, leading to its change into cysteine or histidine (even serine or glycine), occurs in early embryogenesis, resulting in widespread tissue distribution of abnormalities. The post zygotic mutation is responsible for the mosaic pattern of tissue distribution and the extreme variability of clinical changes (Weinstein et al., 1991).
Endocrine and non-endocrine tumors: Somatic mutations of Arg201 or Gln227 have been identified in human growth hormone-secreting pituitary adenomas, (Landis et al., 1989; Landis et al., 1990), ACTH-secreting pituitary adenomas (Williamson et al., 1995; Riminucci et al., 2002), nonfunctioning pituitary tumors (Tordjman et al., 1993), thyroid tumors (Suarez et al., 1991), Leydig cell tumor (Libe et al., 2012), ovarian granulosa cell tumors (Kalfa et al., 2006a), renal cell carcinoma (Kalfa et al., 2006b), hepatocellular carcinoma (Nault et al., 2012) and myelodysplastic syndromes (Bejar et al., 2011). The mutation at codon 201 (Arg into Cys or His) is more frequent that the mutation at 227 (Gln into Arg, His, Lys or Leu).
Fibrous dysplasia of the bone: Fibrous dysplasia (FD) is a benign intramedullary osteofibrous lesion that may involve either one (monostotic FD) or several (polyostotic FD) bones. FD may occur in isolation or as part of the McCune-Albright syndrome or within Mazabrauds syndrome. Some cases of FD have been found to have a somatic GNAS mutation, mainly R201C and R201H (Riminucci et al., 1997), though R201S (Candeliere et al., 1997) and Q227L (Idowu et al., 2007) has also been reported.
Inactivating mutations: The first reports of germ-line inactivating Gsα mutations were reported in 1990 (Patten et al., 1990; Weinstein et al., 1990). Latter on, many different mutations have been described in literature and summarized in the Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff (www.hgmd.cf.ac.uk) as a cause of a hormonal disorder coupled to Gsα activity characterized by PTH renal resistance called Pseudohypoparathyroidism (PHP).
Mutation types include translation initiation mutations, amino acid substitutions, nonsense mutations, inversions, splice site mutations, insertions or deletions (even intragenic or encompassing the whole gene). Mutations are distributed throughout the Gsα coding region. Although each mutation is usually associated to a single kindred, a mutational hot-spot involving 20% of all mutations so far described has been identified within exon 7 (Weinstein et al., 1992; Yu et al., 1995; Yokoyama et al., 1996; Ahmed et al., 1998; Mantovani et al., 2000; Aldred and Trembath, 2000). It is a 4 bp deletion which coincides with a defined consensus sequence for arrest of DNA polymerase a, a region known to be prone to sporadic deletion mutations (Krawczak and Cooper, 1991; Yu et al., 1995). In most cases it has been found as a de novo mutation, thus representing a recurring new mutation rather than a founder effect.
As mentioned above, in some tissues paternal GNAS allele is silenced, leading to a parental-of-origin effect. In case of maternally inherited mutation, AHO is associated with end-organ resistance to the Gsα-mediated action of different hormones, primarily PTH, TSH, gonadotropin, and GHRH. AHO with endocrinopathy is then termed pseudohypoparathyroidism type Ia (PHP-Ia; MIM: 103580) or pseudohypoparathyroidism type Ic (PHP-Ic; MIM: 612462). In contrast, AHO due to paternally inherited mutation transmission lacks biochemical evidence of hormone resistance and is designated as pseudopseudohypoparathyroidism (PPHP; MIM 612463) (Davies and Hughes, 1993; Campbell et al., 1994; Weinstein, 2001; Weinstein et al., 2004) (see below for further details).
An intriguing missense mutation (Iiri et al., 1994; Nakamoto et al., 1996) localized within the highly conserved G5 region of the Gsα, has been identified in two unrelated males who presented with AHO, PTH resistance and testotoxicosis (Iiri et al., 1994). This substitution (A366S) leads to constitutive activation of adenylyl cyclase by causing accelerated release of GDP, thus increasing the fraction of active GTP-bound Gsα. However, while this mutant protein is stable at the reduced temperature of the testis, it is thermolabile at 37°C, resulting in reduced Gsα activity in almost tissues and AHO phenotype.
Progressive Osseous Heteroplasia (POH; MIM: 166350) is defined by cutaneous ossification, characteristically presenting during childhood, that progresses to involve subcutaneous and deep connective tissues, including muscle and fascia, in the absence of multiple features of Albright hereditary osteodystrophy (AHO) or hormone resistance (Kaplan et al., 1994). Most cases of POH are caused by heterozygous paternally-inherited inactivating mutations of GNAS (Shore et al., 2002; Adegbite et al., 2008).
Epigenetic alterations: Loss of methylation at GNAS exon A/B, sometimes combined with epigenetic defects at other GNAS differentially methylated regions has been associated with pseudohypoparathyroidism type Ib (PHP-Ib; MIM: 603233). The familial form of the disease has been shown to be mostly associated with an exon A/B-only methylation defect and a heterozygous 3-kb or 4.4-kb deletion mutation within the closely linked STX16 gene (Bastepe et al., 2003; Linglart et al., 2005), although four families of AD-PHP-Ib associated with NESP55 and NESPas deletions have also been described, the latter leading to the loss of all maternal GNAS imprints (Bastepe et al., 2005; Chillambhi et al., 2010; Richard et al., 2012). The exon A/B region is known as an imprinting control region and is believed to be critical for the tissue-specific imprinting of Gsα in the renal proximal tubules (Weinstein et al., 2001). The sporadic form of PHP-Ib show complete loss of methylation at the NESPas, XLαs and A/B regions, and no other changes in cis- or trans-acting elements have been found to explain this loss of methylation. In the scientific literature six cases have been described in which there is an association between the complete loss of methylation and partial or complete paternal isodisomy of chromosome 20q covering the GNAS locus (Bastepe et al., 2001; Bastepe et al., 2010; Fernandez-Rebollo et al., 2010). And on the other hand, it has been recently published a new trait of inheritance, an autosomal recessive form, explaining the molecular mechanism underlying the sporadic PHP-Ib in five families (Fernandez-Rebollo et al., 2011).

Implicated in

Entity name
McCune-Albright syndrome
Note
The McCune-Albright syndrome (MAS) is a rare, sporadic disease characterized by a classical triad of clinical signs: polyostotic fibrous dysplasia (FD), skin hyperpigmentation (cafe-au-lait spots) and endocrine dysfunction. The major endocrine disorders include autonomous hyperfunction of several endocrine glands, such as gonads, thyroid, pituitary and adrenal cortex, i.e. glands sensitive to trophic agents acting through cAMP dependent pathway. Moreover, increasing data drive the attention to non-endocrine affections, including hepatobiliary dysfunction and cardiac disease, which are probably important risk factors for early death.
As mutation detection rates may vary considerably according to the type of tissue analyzed and the detection method used, sensitive and specific molecular methods must be used to look for the mutation from all available affected tissues and from easily accessible tissues, particularly in the presence of atypical and monosymptomatic forms of MAS (Weinstein, 2006; Chapurlat and Orcel, 2008).
Prognosis
The prognosis depends on the severity of each individual endocrine and non-endocrine manifestation and on the age at which each affection appears.
Bisphosphonates are used in the treatment of FD to relieve bone pain and improve lytic lesions, but they are still under clinical evaluation. Calcium, vitamin D and phosphorus supplements may be useful in some patients. Surgery is also helpful to prevent and treat fracture and deformities.
Oncogenesis
Postzygotic, somatic mutations at Arginine 201 of the GNAS gene that results in cellular mosaicism, thus leading to a broad spectrum of clinical manifestations.
Entity name
Mazabraud syndrome
Note
Very rare association of fibrous dysplasia and myxomas of the soft tissues (Biagini et al., 1987; Dreizin et al., 2012).
Entity name
Various endocrine and non-endocrine tumors
Note
Growth hormone-secreting pituitary adenomas (Landis et al., 1989; Landis et al., 1990), ACTH-secreting pituitary adenomas (Williamson et al., 1995; Riminucci et al., 2002), nonfunctioning pituitary tumors (Tordjman et al., 1993), thyroid tumors (Suarez et al., 1991), Leydig cell tumor (Libe et al., 2012), ovarian granulosa cell tumors (Kalfa et al., 2006a), ACTH-independent macronodular adrenal hyperplasia (AIMAH) (Fragoso et al., 2003), renal cell carcinoma (Kalfa et al., 2006b), hepatocellular carcinoma (Nault et al., 2012) and myelodysplastic syndromes (Bejar et al., 2011).
Activating GNAS mutations are a common feature of the above-mentioned endocrine tumors with a maximum frequency in growth hormone-secreting pituitary adenomas (about 30-40%) (Landis et al., 1989), while the same mutations have been only occasionally reported in the other cited tumors.
Oncogenesis
Activating mutations of the α subunit of the stimulatory G protein (Gsα) gene (the gsp oncogene) leading to amino acid substitution of either residue Arg201 or Gln227. These two residues are catalytically important for GTPase activity, their mutation thus causing constitutive activation by disrupting the signalling turn-off mechanism. Growth and hormone release in many endocrine glands are stimulated by trophic hormones that activate Gsα-cAMP pathways, therefore GNAS activating mutations affect those glands sensitive to trophic agents acting through the cAMP-dependent pathway, leading to autonomous hyperfunction in addition to tumorigenesis.
Entity name
Pseudohypoparathyroidism
Note
Pseudohypoparathyroidism (PHP) is a term applied to a heterogeneous group of disorders whose common feature is end-organ resistance to parathyroid hormone (PTH) (Mantovani, 2011).
PTH resistance, the most clinically evident abnormality, usually develops over the first years of life, with hyperphosphatemia and elevated PTH generally preceding hypocalcemia. Renal function is conserved through life and so seems to be bone mineral density.
- elevated PTH levels
- hyperphosphatemia
- absence of hypercalciuria or impaired renal function
- reduced calcemic and phosphaturic response to injected exogenous PTH
Disease
PHP-Ia: in addition to PTH resistance, is characterized by resistance to other hormones, including TSH, gonadotrophins and GHRH. It is associated with Albrights hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation. Laboratory studies show a decreased cAMP response to infused PTH and defects in activity of the erythrocyte Gs protein (Mantovani, 2011).
Pseudo-PHP (PPHP): is characterized by the physical findings of AHO without hormone resistance. Laboratory studies show a defect in Gs protein activity in erythrocytes (Weinstein et al., 2001).
PHP-Ib: is characterized clinically by isolated renal PTH resistance. Patients usually lack the physical characteristics of AHO and typically show no other endocrine abnormalities, although resistance to TSH has been reported. However, patients may rarely show some features of AHO. Laboratory studies show a decreased cAMP response to infused PTH and, most recently reported, sometimes defects in Gs protein activity similarly to PHP-Ia patients (Zazo et al., 2011; Mantovani et al., 2012).
Progressive Osseous Heteroplasia (POH): is characterized by ectopic dermal ossification beginning in infancy, followed by increasing and extensive bone formation in deep muscle and fascia. These patients typically do not show any endocrine abnormality (Shore et al., 2002; Shore and Kaplan, 2010).
Prognosis
In general, PHP patients should be monitored annually for both blood biochemistries (PTH, calcium, phosphate, TSH) and urinary calcium excretion. Particular attention must be given in children to height, growth velocity and pubertal development. Increasing evidences suggest that, independently of growth curve, children should be screened with appropriate provocative tests for GH deficiency in order to eventually start treatment as soon as possible. Weight and BMI should be checked in order to start dietary/exercise intervention when appropriate. Careful physical examination and, when necessary, specific psychological investigations should be performed annually in order to detect and follow the presence/evolution of specific AHO features (in particular heterotopic ossifications and mental retardation). Initial screening should include radiological evaluation of brachydactyly.
The long-term therapy of hypocalcemia, in order to maintain normocalcemia, is with active vitamin D metabolites, preferentially calcitriol, with or without oral calcium supplementation. Patients should be also routinely screened and eventually treated for any associated endocrinopathy, in particular hypothyroidism and hypogonadism. Levothyroxine and sex hormones should be given following the same criteria, doses and follow-up as in any other form of hypothyroidism or hypogonadism.
There are no specific treatments for the various manifestations of AHO, even if subcutaneous ossifications may be surgically removed when particularly large or bothersome.
While prognosis of correctly treated hormone disturbances is very good, POH may end up with deeply invalidating lesions.
Atlas Image
Table1. Legend: PHP, pseudohypoparathyroidism; PPHP, Pseudo-pseudohypoparathyroidism; AHO, Albright hereditary osteodystrophy; POH, Progressive Osseous Heteroplasia; Gn, gonadotropins; NA, not available.

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 2778
MIM: 139320
HGNC: 4392
Ensembl: ENSG00000087460

Variants:

dbSNP: 2778
ClinVar: 2778
TCGA: ENSG00000087460
COSMIC: GNAS

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000087460ENST00000265620P63092
ENSG00000087460ENST00000306090A0A0A0MR13
ENSG00000087460ENST00000306120P84996
ENSG00000087460ENST00000313949O95467
ENSG00000087460ENST00000338783A2A2R6
ENSG00000087460ENST00000349036Q5JWE9
ENSG00000087460ENST00000354359P63092
ENSG00000087460ENST00000371075O95467
ENSG00000087460ENST00000371081Q5JWD1
ENSG00000087460ENST00000371085P63092
ENSG00000087460ENST00000371085A0A0S2Z3H8
ENSG00000087460ENST00000371095P63092
ENSG00000087460ENST00000371095A0A0S2Z3S5
ENSG00000087460ENST00000371098O95467
ENSG00000087460ENST00000371099X6R7U9
ENSG00000087460ENST00000371100Q5JWF2
ENSG00000087460ENST00000371102Q5JWF2
ENSG00000087460ENST00000419558H0Y7Z6
ENSG00000087460ENST00000423897H0Y7E8
ENSG00000087460ENST00000450130H0Y7F4
ENSG00000087460ENST00000453292A2A2S1
ENSG00000087460ENST00000461152A0A590UJ46
ENSG00000087460ENST00000462499A0A590UKA1
ENSG00000087460ENST00000464624A0A590UJX6
ENSG00000087460ENST00000464788A0A590UJ22
ENSG00000087460ENST00000464960A0A590UJX3
ENSG00000087460ENST00000467227A0A590UK28
ENSG00000087460ENST00000467321A0A590UJQ2
ENSG00000087460ENST00000468895A0A590UJS2
ENSG00000087460ENST00000469431A0A590UJY8
ENSG00000087460ENST00000470512A0A590UJQ9
ENSG00000087460ENST00000472183S4R3E3
ENSG00000087460ENST00000476935A0A590UJG5
ENSG00000087460ENST00000477931B0AZR9
ENSG00000087460ENST00000478585A0A590UKA9
ENSG00000087460ENST00000480232A0A590UJR6
ENSG00000087460ENST00000480975A0A590UJF0
ENSG00000087460ENST00000481039A0A590UKB4
ENSG00000087460ENST00000481768A0A590UK00
ENSG00000087460ENST00000482112A0A590UKA4
ENSG00000087460ENST00000484504A0A590UJ47
ENSG00000087460ENST00000485673A0A590UJA5
ENSG00000087460ENST00000488546A0A590UJB0
ENSG00000087460ENST00000488652A0A590UJI6
ENSG00000087460ENST00000491348A0A590UJ47
ENSG00000087460ENST00000492907A0A590UJJ0
ENSG00000087460ENST00000493744A0A590UJX3
ENSG00000087460ENST00000494081A0A590UJC9
ENSG00000087460ENST00000603546S4R3V9
ENSG00000087460ENST00000604005S4R3E3
ENSG00000087460ENST00000656419A0A590UJY2
ENSG00000087460ENST00000657090B0AZR9
ENSG00000087460ENST00000663479A0A590UJB7
ENSG00000087460ENST00000667293A0A590UJ58

Expression (GTEx)

0
500
1000
1500

Pathways

PathwaySourceExternal ID
Calcium signaling pathwayKEGGko04020
Gap junctionKEGGko04540
Long-term depressionKEGGko04730
GnRH signaling pathwayKEGGko04912
MelanogenesisKEGGko04916
Vibrio cholerae infectionKEGGko05110
Calcium signaling pathwayKEGGhsa04020
Gap junctionKEGGhsa04540
Long-term depressionKEGGhsa04730
GnRH signaling pathwayKEGGhsa04912
MelanogenesisKEGGhsa04916
Vibrio cholerae infectionKEGGhsa05110
Pathways in cancerKEGGhsa05200
Vascular smooth muscle contractionKEGGhsa04270
Vascular smooth muscle contractionKEGGko04270
Dilated cardiomyopathyKEGGko05414
Dilated cardiomyopathyKEGGhsa05414
Vasopressin-regulated water reabsorptionKEGGko04962
Vasopressin-regulated water reabsorptionKEGGhsa04962
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
Salivary secretionKEGGko04970
Salivary secretionKEGGhsa04970
Gastric acid secretionKEGGko04971
Gastric acid secretionKEGGhsa04971
AmoebiasisKEGGko05146
AmoebiasisKEGGhsa05146
Pancreatic secretionKEGGko04972
Pancreatic secretionKEGGhsa04972
Bile secretionKEGGko04976
Bile secretionKEGGhsa04976
Endocrine and other factor-regulated calcium reabsorptionKEGGko04961
Endocrine and other factor-regulated calcium reabsorptionKEGGhsa04961
Glutamatergic synapseKEGGko04724
Glutamatergic synapseKEGGhsa04724
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Serotonergic synapseKEGGhsa04726
Cocaine addictionKEGGhsa05030
Cocaine addictionKEGGko05030
Amphetamine addictionKEGGhsa05031
Amphetamine addictionKEGGko05031
Morphine addictionKEGGhsa05032
Morphine addictionKEGGko05032
AlcoholismKEGGhsa05034
AlcoholismKEGGko05034
Circadian entrainmentKEGGhsa04713
Circadian entrainmentKEGGko04713
Insulin secretionKEGGhsa04911
Ovarian steroidogenesisKEGGhsa04913
Ovarian steroidogenesisKEGGko04913
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
Thyroid hormone synthesisKEGGhsa04918
Thyroid hormone synthesisKEGGko04918
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Adrenergic signaling in cardiomyocytesKEGGhsa04261
Adrenergic signaling in cardiomyocytesKEGGko04261
Inflammatory mediator regulation of TRP channelsKEGGhsa04750
Inflammatory mediator regulation of TRP channelsKEGGko04750
Platelet activationKEGGhsa04611
Oxytocin signaling pathwayKEGGhsa04921
Oxytocin signaling pathwayKEGGko04921
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
cAMP signalingKEGGhsa_M00695
cAMP signalingKEGGM00695
Glucagon signaling pathwayKEGGhsa04922
Glucagon signaling pathwayKEGGko04922
Regulation of lipolysis in adipocytesKEGGhsa04923
Renin secretionKEGGhsa04924
Renin secretionKEGGko04924
HemostasisREACTOMER-HSA-109582
Platelet homeostasisREACTOMER-HSA-418346
Prostacyclin signalling through prostacyclin receptorREACTOMER-HSA-392851
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class B/2 (Secretin family receptors)REACTOMER-HSA-373080
Glucagon-type ligand receptorsREACTOMER-HSA-420092
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (s) signalling eventsREACTOMER-HSA-418555
G alpha (i) signalling eventsREACTOMER-HSA-418594
G alpha (z) signalling eventsREACTOMER-HSA-418597
Signaling by HedgehogREACTOMER-HSA-5358351
Hedgehog 'off' stateREACTOMER-HSA-5610787
Transmembrane transport of small moleculesREACTOMER-HSA-382551
Aquaporin-mediated transportREACTOMER-HSA-445717
Vasopressin regulates renal water homeostasis via AquaporinsREACTOMER-HSA-432040
MetabolismREACTOMER-HSA-1430728
Integration of energy metabolismREACTOMER-HSA-163685
Regulation of insulin secretionREACTOMER-HSA-422356
Glucagon-like Peptide-1 (GLP1) regulates insulin secretionREACTOMER-HSA-381676
Glucagon signaling in metabolic regulationREACTOMER-HSA-163359
PKA activation in glucagon signallingREACTOMER-HSA-164378
Aldosterone synthesis and secretionKEGGhsa04925
Aldosterone synthesis and secretionKEGGko04925
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164741137ADCY3GenePathwayassociated20938371
PA24560ADCY1GenePathwayassociated19741567
PA24561ADCY2GenePathwayassociated19741567
PA24562ADCY4GenePathwayassociated
PA24563ADCY5GenePathwayassociated
PA27ADCY6GenePathwayassociated
PA28ADCY7GenePathwayassociated
PA285PTGDRGenePathwayassociated20938371
PA287PTGER2GenePathwayassociated20938371
PA29ADCY8GenePathwayassociated
PA291PTGIRGenePathwayassociated20938371
PA29457HRH2GenePathwayassociated
PA29557HTR4GenePathwayassociated19741567
PA29560HTR6GenePathwayassociated19741567
PA29561HTR7GenePathwayassociated19741567
PA30ADCY9GenePathwayassociated
PA34361RGS1GenePathwayassociated
PA39ADRB2GenePathwayassociated
PA449381dobutamineChemicalClinicalAnnotationassociatedPD19542315

References

Pubmed IDYearTitleCitations
378283972024The mystery of transient pregnancy-induced cushing's syndrome: a case report and literature review highlighting GNAS somatic mutations and LHCGR overexpression.0
380977402024Compartment-specific multiomic profiling identifies SRC and GNAS as candidate drivers of epithelial-to-mesenchymal transition in ovarian carcinosarcoma.1
382459232024DNA methylation landscape reveals GNAS as a decitabine-responsive marker in patients with acute myeloid leukemia.0
382900082024GNAS AS2 methylation status enables mechanism-based categorization of pseudohypoparathyroidism type 1B.0
383191572024GNAS mutation inhibits growth and induces phosphodiesterase 4D expression in colorectal cancer cell lines.0
383192862024Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.0
383756342024Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.0
384808812024Time-resolved cryo-EM of G-protein activation by a GPCR.6
386646772024Identification of a novel GNAS mutation in a family with pseudohypoparathyroidism type 1A.0
378283972024The mystery of transient pregnancy-induced cushing's syndrome: a case report and literature review highlighting GNAS somatic mutations and LHCGR overexpression.0
380977402024Compartment-specific multiomic profiling identifies SRC and GNAS as candidate drivers of epithelial-to-mesenchymal transition in ovarian carcinosarcoma.1
382459232024DNA methylation landscape reveals GNAS as a decitabine-responsive marker in patients with acute myeloid leukemia.0
382900082024GNAS AS2 methylation status enables mechanism-based categorization of pseudohypoparathyroidism type 1B.0
383191572024GNAS mutation inhibits growth and induces phosphodiesterase 4D expression in colorectal cancer cell lines.0
383192862024Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.0

Citation

Guiomar Pérez de Nanclares ; Giovanna Mantovani ; Eduardo Fernandez-Rebollo

GNAS (GNAS complex locus)

Atlas Genet Cytogenet Oncol Haematol. 2012-10-01

Online version: http://atlasgeneticsoncology.org/gene/40727/img/teaching-explorer/js/lib/bootstrap.min.js