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GNAS (GNAS complex locus)

Written2012-10Guiomar Pérez de Nanclares, Giovanna Mantovani, Eduardo Fernandez-Rebollo
Molecular (Epi)Genetics Laboratory, Research Unit, Hospital Universitario Araba-Txagorritxu, C/Jose Atxotegi s/n, Q2 Vitoria-Gasteiz, Alava, Spain (GPN); Endocrinology Unit, Deparment of Clinical Sciences, Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, Milan, Italy (GM); Diabetes, Obesity Laboratory, Endocrinology, Nutrition Unit, Institut d'Investigations Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Spain (EFR)

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HGNC Alias symbNESP55
HGNC Alias namesecretogranin VI
 G protein subunit alpha S
HGNC Previous nameGNAS1
HGNC Previous nameguanine nucleotide binding protein (G protein), alpha stimulating activity polypeptide 1
LocusID (NCBI) 2778
Atlas_Id 40727
Location 20q13.32  [Link to chromosome band 20q13]
Location_base_pair Starts at 58891421 and ends at 58911188 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping GNAS.png]
  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).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACTB (7p22.1)::GNAS (20q13.32)ALG6 (1p31.3)::GNAS (20q13.32)CUX1 (7q22.1)::GNAS (20q13.32)
ENC1 (5q13.3)::GNAS (20q13.32)FGB (4q31.3)::GNAS (20q13.32)GNAS (20q13.32)::CHMP2A (19q13.43)
GNAS (20q13.32)::EAF1 (3p25.1)GNAS (20q13.32)::FHIT (3p14.2)GNAS (20q13.32)::GNAS (20q13.32)
GNAS (20q13.32)::STK38L (12p11.23)GNAS (20q13.32)::TRIM61 (4q32.3)HAPLN1 (5q14.3)::GNAS (20q13.32)
HEG1 (3q21.2)::GNAS (20q13.32)IRF3 (19q13.33)::GNAS (20q13.32)KIAA0319L (1p34.3)::GNAS (20q13.32)
LAPTM4A (2p24.1)::GNAS (20q13.32)LOC100130331 (1q43)::GNAS (20q13.32)NDUFS6 (5p15.33)::GNAS (20q13.32)
PTGS1 (9q33.2)::GNAS (20q13.32)PTPRN (2q35)::GNAS (20q13.32)SKA2 (17q22)::GNAS (20q13.32)
TUBGCP3 (13q34)::GNAS (20q13.32)WDR33 (2q14.3)::GNAS (20q13.32)ZBTB20 (3q13.31)::GNAS (20q13.32)
Note The gene encoding the Gsα protein gene GNAS (Guanine Nucleotide binding protein, Alpha Stimulating) is located in one of the most complex locus of the human genome, the GNAS locus, on the long arm of chromosome 20 (20q13.32) (Gejman et al., 1991). The complexity of this locus does not lie only in the four alternative first exons splicing onto common exons 2 to 13, or the antisense transcript that resides in this locus, but this locus also presents an elaborated imprinting pattern. The genomic imprinting is an epigenetic process in which a specific imprint mark is erased in primordial germ cells and then reestablished during oogenesis or spermatogenesis, resulting in suppression of gene expression from one parental allele (Reik and Walter, 2001). This differential gene expression may take whole lifetime or just a limited developmental stage, and can be generalized to all tissues that express the gene or may be tissue dependent (Latham, 1995; Solter, 1998). In most cases, the methylation of the allele is the imprinting mark (addition of methyl groups on cytosine in the CpG dinucleotides), but other times, the imprinting mechanism remains unknown.


  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 5'splice 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.


  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).


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 Mazabraud's 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 ( 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 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 Mazabraud syndrome
Note Very rare association of fibrous dysplasia and myxomas of the soft tissues (Biagini et al., 1987; Dreizin et al., 2012).
Entity 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 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.
Diagnostic Criteria for PHP:
- elevated PTH levels
- hypocalcemia
- 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 Albright's 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).
PHP-Ic: is clinically indistinguishable from PHP-Ia, therefore being characterized by the association of multi-hormone resistance and AHO. Laboratory studies show a decreased cAMP response to infused PTH, but typically no defect in activity of the erythrocyte Gs protein (Thiele et al., 2011).
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.
Table1. Legend: PHP, pseudohypoparathyroidism; PPHP, Pseudo-pseudohypoparathyroidism; AHO, Albright hereditary osteodystrophy; POH, Progressive Osseous Heteroplasia; Gn, gonadotropins; NA, not available.


Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification.
Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ.
Am J Med Genet A. 2008 Jul 15;146A(14):1788-96. doi: 10.1002/ajmg.a.32346.
PMID 18553568
GNAS1 mutational analysis in pseudohypoparathyroidism.
Ahmed SF, Dixon PH, Bonthron DT, Stirling HF, Barr DG, Kelnar CJ, Thakker RV.
Clin Endocrinol (Oxf). 1998 Oct;49(4):525-31.
PMID 9876352
Activating and inactivating mutations in the human GNAS1 gene.
Aldred MA, Trembath RC.
Hum Mutat. 2000 Sep;16(3):183-9. (REVIEW)
PMID 10980525
Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib).
Bastepe M, Altug-Teber O, Agarwal C, Oberfield SE, Bonin M, Juppner H.
Bone. 2011 Mar 1;48(3):659-62. doi: 10.1016/j.bone.2010.10.168. Epub 2010 Oct 19.
PMID 20965295
Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib.
Bastepe M, Frohlich LF, Linglart A, Abu-Zahra HS, Tojo K, Ward LM, Juppner H.
Nat Genet. 2005 Jan;37(1):25-7. Epub 2004 Dec 12.
PMID 15592469
Paternal uniparental isodisomy of chromosome 20q--and the resulting changes in GNAS1 methylation--as a plausible cause of pseudohypoparathyroidism.
Bastepe M, Lane AH, Juppner H.
Am J Hum Genet. 2001 May;68(5):1283-9. Epub 2001 Apr 9.
PMID 11294659
Clinical effect of point mutations in myelodysplastic syndromes.
Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL.
N Engl J Med. 2011 Jun 30;364(26):2496-506. doi: 10.1056/NEJMoa1013343.
PMID 21714648
The Mazabraud syndrome: case report and review of the literature.
Biagini R, Ruggieri P, Boriani S, Picci P.
Ital J Orthop Traumatol. 1987 Mar;13(1):105-11. (REVIEW)
PMID 3319954
Human cDNA clones for four species of G alpha s signal transduction protein.
Bray P, Carter A, Simons C, Guo V, Puckett C, Kamholz J, Spiegel A, Nirenberg M.
Proc Natl Acad Sci U S A. 1986 Dec;83(23):8893-7.
PMID 3024154
Insights into G protein structure, function, and regulation.
Cabrera-Vera TM, Vanhauwe J, Thomas TO, Medkova M, Preininger A, Mazzoni MR, Hamm HE.
Endocr Rev. 2003 Dec;24(6):765-81. (REVIEW)
PMID 14671004
Parental origin of transcription from the human GNAS1 gene.
Campbell R, Gosden CM, Bonthron DT.
J Med Genet. 1994 Aug;31(8):607-14.
PMID 7815417
Polymerase chain reaction-based technique for the selective enrichment and analysis of mosaic arg201 mutations in G alpha s from patients with fibrous dysplasia of bone.
Candeliere GA, Roughley PJ, Glorieux FH.
Bone. 1997 Aug;21(2):201-6.
PMID 9267696
Fibrous dysplasia of bone and McCune-Albright syndrome.
Chapurlat RD, Orcel P.
Best Pract Res Clin Rheumatol. 2008 Mar;22(1):55-69. doi: 10.1016/j.berh.2007.11.004. (REVIEW)
PMID 18328981
Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha-Ggamma interactions.
Cherfils J, Chabre M.
Trends Biochem Sci. 2003 Jan;28(1):13-7.
PMID 12517447
Deletion of the noncoding GNAS antisense transcript causes pseudohypoparathyroidism type Ib and biparental defects of GNAS methylation in cis.
Chillambhi S, Turan S, Hwang DY, Chen HC, Juppner H, Bastepe M.
J Clin Endocrinol Metab. 2010 Aug;95(8):3993-4002. doi: 10.1210/jc.2009-2205. Epub 2010 May 5.
PMID 20444925
Imprinting in Albright's hereditary osteodystrophy.
Davies SJ, Hughes HE.
J Med Genet. 1993 Feb;30(2):101-3. (REVIEW)
PMID 8383205
Mazabraud syndrome.
Dreizin D, Glen C, Jose J.
Am J Orthop (Belle Mead NJ). 2012 Jul;41(7):332-5.
PMID 22893885
Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib?
Fernandez-Rebollo E, Perez de Nanclares G, Lecumberri B, Turan S, Anda E, Perez-Nanclares G, Feig D, Nik-Zainal S, Bastepe M, Juppner H.
J Bone Miner Res. 2011 Aug;26(8):1854-63. doi: 10.1002/jbmr.408.
PMID 21523828
Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene.
Fragoso MC, Domenice S, Latronico AC, Martin RM, Pereira MA, Zerbini MC, Lucon AM, Mendonca BB.
J Clin Endocrinol Metab. 2003 May;88(5):2147-51.
PMID 12727968
Genetic mapping of the Gs-alpha subunit gene (GNAS1) to the distal long arm of chromosome 20 using a polymorphism detected by denaturing gradient gel electrophoresis.
Gejman PV, Weinstein LS, Martinez M, Spiegel AM, Cao Q, Hsieh WT, Hoehe MR, Gershon ES.
Genomics. 1991 Apr;9(4):782-3.
PMID 1674732
Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a.
Germain-Lee EL, Ding CL, Deng Z, Crane JL, Saji M, Ringel MD, Levine MA.
Biochem Biophys Res Commun. 2002 Aug 9;296(1):67-72.
PMID 12147228
Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly.
Hayward BE, Barlier A, Korbonits M, Grossman AB, Jacquet P, Enjalbert A, Bonthron DT.
J Clin Invest. 2001 Mar;107(6):R31-6.
PMID 11254676
A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone.
Idowu BD, Al-Adnani M, O'Donnell P, Yu L, Odell E, Diss T, Gale RE, Flanagan AM.
Histopathology. 2007 May;50(6):691-704.
PMID 17493233
Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function.
Iiri T, Herzmark P, Nakamoto JM, van Dop C, Bourne HR.
Nature. 1994 Sep 8;371(6493):164-8.
PMID 8072545
Molecular cloning and characterization of NESP55, a novel chromogranin-like precursor of a peptide with 5-HT1B receptor antagonist activity.
Ischia R, Lovisetti-Scamihorn P, Hogue-Angeletti R, Wolkersdorfer M, Winkler H, Fischer-Colbrie R.
J Biol Chem. 1997 Apr 25;272(17):11657-62.
PMID 9111083
Alternative promoter and 5' exon generate a novel Gs alpha mRNA.
Ishikawa Y, Bianchi C, Nadal-Ginard B, Homcy CJ.
J Biol Chem. 1990 May 25;265(15):8458-62.
PMID 2111318
Activating mutations of the stimulatory g protein in juvenile ovarian granulosa cell tumors: a new prognostic factor?
Kalfa N, Ecochard A, Patte C, Duvillard P, Audran F, Pienkowski C, Thibaud E, Brauner R, Lecointre C, Plantaz D, Guedj AM, Paris F, Baldet P, Lumbroso S, Sultan C.
J Clin Endocrinol Metab. 2006a May;91(5):1842-7. Epub 2006 Feb 28.
PMID 16507630
Activating mutations of Gsalpha in kidney cancer.
Kalfa N, Lumbroso S, Boulle N, Guiter J, Soustelle L, Costa P, Chapuis H, Baldet P, Sultan C.
J Urol. 2006b Sep;176(3):891-5.
PMID 16890646
Progressive osseous heteroplasia: a distinct developmental disorder of heterotopic ossification. Two new case reports and follow-up of three previously reported cases.
Kaplan FS, Craver R, MacEwen GD, Gannon FH, Finkel G, Hahn G, Tabas J, Gardner RJ, Zasloff MA.
J Bone Joint Surg Am. 1994 Mar;76(3):425-36. (REVIEW)
PMID 8126048
XL alpha s is a new type of G protein.
Kehlenbach RH, Matthey J, Huttner WB.
Nature. 1994 Dec 22-29;372(6508):804-9.
PMID 7997272
Galpha(s) is palmitoylated at the N-terminal glycine.
Kleuss C, Krause E.
EMBO J. 2003 Feb 17;22(4):826-32.
PMID 12574119
Isolation and characterization of the human Gs alpha gene.
Kozasa T, Itoh H, Tsukamoto T, Kaziro Y.
Proc Natl Acad Sci U S A. 1988 Apr;85(7):2081-5.
PMID 3127824
Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment.
Krawczak M, Cooper DN.
Hum Genet. 1991 Mar;86(5):425-41.
PMID 2016084
Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein.
Landis CA, Harsh G, Lyons J, Davis RL, McCormick F, Bourne HR.
J Clin Endocrinol Metab. 1990 Dec;71(6):1416-20.
PMID 2121775
GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours.
Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L.
Nature. 1989 Aug 31;340(6236):692-6.
PMID 2549426
G protein mutations in endocrine diseases.
Lania A, Mantovani G, Spada A.
Eur J Endocrinol. 2001 Nov;145(5):543-59. (REVIEW)
PMID 11720871
Stage-specific and cell type-specific aspects of genomic imprinting effects in mammals.
Latham KE.
Differentiation. 1995 Dec;59(5):269-82. (REVIEW)
PMID 8882812
A rare cause of hypertestosteronemia in a 68-year-old patient: a Leydig cell tumor due to a somatic GNAS (guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1)-activating mutation.
Libe R, Fratticci A, Lahlou N, Jornayvaz FR, Tissier F, Louiset E, Guibourdenche J, Vieillefond A, Zerbib M, Bertherat J.
J Androl. 2012 Jul-Aug;33(4):578-84. doi: 10.2164/jandrol.111.013441. Epub 2011 Oct 20.
PMID 22016347
A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS.
Linglart A, Gensure RC, Olney RC, Juppner H, Bastepe M.
Am J Hum Genet. 2005 May;76(5):804-14. Epub 2005 Mar 30.
PMID 15800843
Identification of the control region for tissue-specific imprinting of the stimulatory G protein alpha-subunit.
Liu J, Chen M, Deng C, Bourc'his D, Nealon JG, Erlichman B, Bestor TH, Weinstein LS.
Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5513-8. Epub 2005 Apr 5.
PMID 15811946
The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B.
Liu J, Erlichman B, Weinstein LS.
J Clin Endocrinol Metab. 2003 Sep;88(9):4336-41.
PMID 12970307
A GNAS1 imprinting defect in pseudohypoparathyroidism type IB.
Liu J, Litman D, Rosenberg MJ, Yu S, Biesecker LG, Weinstein LS.
J Clin Invest. 2000 Nov;106(9):1167-74.
PMID 11067869
GNAS epigenetic defects and pseudohypoparathyroidism: time for a new classification?
Mantovani G, Elli FM, Spada A.
Horm Metab Res. 2012 Sep;44(10):716-23. doi: 10.1055/s-0032-1314842. Epub 2012 Jun 6.
PMID 22674477
Clinical review: Pseudohypoparathyroidism: diagnosis and treatment.
Mantovani G.
J Clin Endocrinol Metab. 2011 Oct;96(10):3020-30. doi: 10.1210/jc.2011-1048. Epub 2011 Aug 3. (REVIEW)
PMID 21816789
Concurrent hormone resistance (pseudohypoparathyroidism type Ia) and hormone independence (testotoxicosis) caused by a unique mutation in the G alpha s gene.
Nakamoto JM, Zimmerman D, Jones EA, Loke KY, Siddiq K, Donlan MA, Brickman AS, Van Dop C.
Biochem Mol Med. 1996 Jun;58(1):18-24.
PMID 8809352
GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation.
Nault JC, Fabre M, Couchy G, Pilati C, Jeannot E, Tran Van Nhieu J, Saint-Paul MC, De Muret A, Redon MJ, Buffet C, Salenave S, Balabaud C, Prevot S, Labrune P, Bioulac-Sage P, Scoazec JY, Chanson P, Zucman-Rossi J.
J Hepatol. 2012 Jan;56(1):184-91. doi: 10.1016/j.jhep.2011.07.018. Epub 2011 Aug 9.
PMID 21835143
Structure and function of G proteins.
Olate J, Allende JE.
Pharmacol Ther. 1991;51(3):403-19. (REVIEW)
PMID 1792242
Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy.
Patten JL, Johns DR, Valle D, Eil C, Gruppuso PA, Steele G, Smallwood PM, Levine MA.
N Engl J Med. 1990 May 17;322(20):1412-9.
PMID 2109828
GTP-binding proteins. 1: heterotrimeric G proteins.
Pennington SR.
Protein Profile. 1994;1(3):169-342. (REVIEW)
PMID 8528903
A cluster of oppositely imprinted transcripts at the Gnas locus in the distal imprinting region of mouse chromosome 2.
Peters J, Wroe SF, Wells CA, Miller HJ, Bodle D, Beechey CV, Williamson CM, Kelsey G.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3830-5.
PMID 10097123
Genomic imprinting: parental influence on the genome.
Reik W, Walter J.
Nat Rev Genet. 2001 Jan;2(1):21-32. (REVIEW)
PMID 11253064
A new deletion ablating NESP55 causes loss of maternal imprint of A/B GNAS and autosomal dominant pseudohypoparathyroidism type Ib.
Richard N, Abeguile G, Coudray N, Mittre H, Gruchy N, Andrieux J, Cathebras P, Kottler ML.
J Clin Endocrinol Metab. 2012 May;97(5):E863-7. doi: 10.1210/jc.2011-2804. Epub 2012 Feb 29.
PMID 22378814
An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph pituitary adenoma.
Riminucci M, Collins MT, Lala R, Corsi A, Matarazzo P, Gehron Robey P, Bianco P.
Mol Pathol. 2002 Feb;55(1):58-60.
PMID 11836449
Receptors coupled to heterotrimeric G proteins of the G12 family.
Riobo NA, Manning DR.
Trends Pharmacol Sci. 2005 Mar;26(3):146-54. (REVIEW)
PMID 15749160
Molecular basis for two forms of the G protein that stimulates adenylate cyclase.
Robishaw JD, Smigel MD, Gilman AG.
J Biol Chem. 1986 Jul 25;261(21):9587-90.
PMID 3015900
Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia.
Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA, Kaplan FS.
N Engl J Med. 2002 Jan 10;346(2):99-106.
PMID 11784876
Inherited human diseases of heterotopic bone formation.
Shore EM, Kaplan FS.
Nat Rev Rheumatol. 2010 Sep;6(9):518-27. doi: 10.1038/nrrheum.2010.122. Epub 2010 Aug 10. (REVIEW)
PMID 20703219
Solter D.
Int J Dev Biol. 1998;42(7):951-4. (REVIEW)
PMID 9853826
Inherited diseases involving g proteins and g protein-coupled receptors.
Spiegel AM, Weinstein LS.
Annu Rev Med. 2004;55:27-39. (REVIEW)
PMID 14746508
Hormone resistance caused by mutations in G proteins and G protein-coupled receptors.
Spiegel AM.
J Pediatr Endocrinol Metab. 1999 Apr;12 Suppl 1:303-9. (REVIEW)
PMID 10698594
gsp mutations in human thyroid tumours.
Suarez HG, du Villard JA, Caillou B, Schlumberger M, Parmentier C, Monier R.
Oncogene. 1991 Apr;6(4):677-9.
PMID 1903197
Differential expression of novel Gs alpha signal transduction protein cDNA species.
Swaroop A, Agarwal N, Gruen JR, Bick D, Weissman SM.
Nucleic Acids Res. 1991 Sep 11;19(17):4725-9.
PMID 1716359
Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα-receptor interaction.
Thiele S, de Sanctis L, Werner R, Grotzinger J, Aydin C, Juppner H, Bastepe M, Hiort O.
Hum Mutat. 2011 Jun;32(6):653-60. doi: 10.1002/humu.21489. Epub 2011 Apr 12.
PMID 21488135
Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.
Tordjman K, Stern N, Ouaknine G, Yossiphov Y, Razon N, Nordenskjold M, Friedman E.
J Clin Endocrinol Metab. 1993 Sep;77(3):765-9.
PMID 8396579
G(s)alpha mutations in fibrous dysplasia and McCune-Albright syndrome.
Weinstein LS.
J Bone Miner Res. 2006 Dec;21 Suppl 2:P120-4. (REVIEW)
PMID 17229000
A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas.
Williamson CM, Ball ST, Nottingham WT, Skinner JA, Plagge A, Turner MD, Powles N, Hough T, Papworth D, Fraser WD, Maconochie M, Peters J.
Nat Genet. 2004 Aug;36(8):894-9. Epub 2004 Jul 25.
PMID 15273687
G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas.
Williamson EA, Ince PG, Harrison D, Kendall-Taylor P, Harris PE.
Eur J Clin Invest. 1995 Feb;25(2):128-31.
PMID 7737262
A 4-base pair deletion mutation of Gs alpha gene in a Japanese patient with pseudohypoparathyroidism.
Yokoyama M, Takeda K, Iyota K, Okabayashi T, Hashimoto K.
J Endocrinol Invest. 1996 Apr;19(4):236-41.
PMID 8862504
Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene.
Yu S, Yu D, Lee E, Eckhaus M, Lee R, Corria Z, Accili D, Westphal H, Weinstein LS.
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8715-20.
PMID 9671744
Gsα activity is reduced in erythrocyte membranes of patients with psedohypoparathyroidism due to epigenetic alterations at the GNAS locus.
Zazo C, Thiele S, Martin C, Fernandez-Rebollo E, Martinez-Indart L, Werner R, Garin I; Spanish PHP Group, Hiort O, Perez de Nanclares G.
J Bone Miner Res. 2011 Aug;26(8):1864-70. doi: 10.1002/jbmr.369.
PMID 21351142
Galphas transcripts are biallelically expressed in the human kidney cortex: implications for pseudohypoparathyroidism type 1b.
Zheng H, Radeva G, McCann JA, Hendy GN, Goodyer CG.
J Clin Endocrinol Metab. 2001 Oct;86(10):4627-9.
PMID 11600515


This paper should be referenced as such :
Pérez, de Nanclares G ; Mantovani, G ; Fernandez-Rebollo, E
GNAS (GNAS complex locus)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(3):178-187.
Free journal version : [ pdf ]   [ DOI ]

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  McCune Albright syndrome

External links


HGNC (Hugo)GNAS   4392
Entrez_Gene (NCBI)GNAS    GNAS complex locus
AliasesAHO; C20orf45; GNAS1; GPSA; 
GeneCards (Weizmann)GNAS
Ensembl hg19 (Hinxton)ENSG00000087460 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000087460 [Gene_View]  ENSG00000087460 [Sequence]  chr20:58891421-58911188 [Contig_View]  GNAS [Vega]
ICGC DataPortalENSG00000087460
Genatlas (Paris)GNAS
SOURCE (Princeton)GNAS
Genetics Home Reference (NIH)GNAS
Genomic and cartography
GoldenPath hg38 (UCSC)GNAS  -     chr20:58891421-58911188 +  20q13.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GNAS  -     20q13.32   [Description]    (hg19-Feb_2009)
GoldenPathGNAS - 20q13.32 [CytoView hg19]  GNAS - 20q13.32 [CytoView hg38]
Genome Data Viewer NCBIGNAS [Mapview hg19]  
OMIM103580   139320   166350   174800   219080   603233   612462   612463   617686   
Gene and transcription
Genbank (Entrez)AA948160 AF064092 AF088184 AF088185 AF105253
RefSeq transcript (Entrez)NM_000516 NM_001077488 NM_001077489 NM_001077490 NM_001309840 NM_001309842 NM_001309861 NM_001309883 NM_016592 NM_080425 NM_080426
Consensus coding sequences : CCDS (NCBI)GNAS
Gene ExpressionGNAS [ NCBI-GEO ]   GNAS [ EBI - ARRAY_EXPRESS ]   GNAS [ SEEK ]   GNAS [ MEM ]
Gene Expression Viewer (FireBrowse)GNAS [ Firebrowse - Broad ]
GenevisibleExpression of GNAS in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2778
GTEX Portal (Tissue expression)GNAS
Human Protein AtlasENSG00000087460-GNAS [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ5JWF2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ5JWF2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ5JWF2
Domaine pattern : Prosite (Expaxy)G_ALPHA (PS51882)   
Domains : Interpro (EBI)Gprotein_alpha_S    Gprotein_alpha_su    GproteinA_insert    P-loop_NTPase   
Domain families : Pfam (Sanger)G-alpha (PF00503)   
Domain families : Pfam (NCBI)pfam00503   
Domain families : Smart (EMBL)G_alpha (SM00275)  
Conserved Domain (NCBI)GNAS
AlphaFold pdb e-kbQ5JWF2   
Human Protein Atlas [tissue]ENSG00000087460-GNAS [tissue]
Protein Interaction databases
IntAct (EBI)Q5JWF2
Ontologies - Pathways
Ontology : AmiGOG protein-coupled receptor binding  GTPase activity  insulin-like growth factor receptor binding  protein binding  GTP binding  cytosol  cytosol  heterotrimeric G-protein complex  adenylate cyclase-modulating G protein-coupled receptor signaling pathway  adenylate cyclase-activating G protein-coupled receptor signaling pathway  adenylate cyclase-activating dopamine receptor signaling pathway  sensory perception of chemical stimulus  adenylate cyclase activator activity  membrane  membrane  membrane  apical plasma membrane  G-protein beta/gamma-subunit complex binding  beta-2 adrenergic receptor binding  D1 dopamine receptor binding  mu-type opioid receptor binding  ionotropic glutamate receptor binding  metal ion binding  developmental growth  corticotropin-releasing hormone receptor 1 binding  bone development  extracellular exosome  platelet aggregation  positive regulation of cold-induced thermogenesis  
Ontology : EGO-EBIG protein-coupled receptor binding  GTPase activity  insulin-like growth factor receptor binding  protein binding  GTP binding  cytosol  cytosol  heterotrimeric G-protein complex  adenylate cyclase-modulating G protein-coupled receptor signaling pathway  adenylate cyclase-activating G protein-coupled receptor signaling pathway  adenylate cyclase-activating dopamine receptor signaling pathway  sensory perception of chemical stimulus  adenylate cyclase activator activity  membrane  membrane  membrane  apical plasma membrane  G-protein beta/gamma-subunit complex binding  beta-2 adrenergic receptor binding  D1 dopamine receptor binding  mu-type opioid receptor binding  ionotropic glutamate receptor binding  metal ion binding  developmental growth  corticotropin-releasing hormone receptor 1 binding  bone development  extracellular exosome  platelet aggregation  positive regulation of cold-induced thermogenesis  
Pathways : BIOCARTAChREBP regulation by carbohydrates and cAMP [Genes]    Erk1/Erk2 Mapk Signaling pathway [Genes]    Corticosteroids and cardioprotection [Genes]    Roles of ?-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling [Genes]    ?-arrestins in GPCR Desensitization [Genes]    Ion Channels and Their Functional Role in Vascular Endothelium [Genes]    Attenuation of GPCR Signaling [Genes]    Role of ?-arrestins in the activation and targeting of MAP kinases [Genes]    CCR3 signaling in Eosinophils [Genes]   
Pathways : KEGGRap1 signaling pathway    Calcium signaling pathway    Adrenergic signaling in cardiomyocytes    Vascular smooth muscle contraction    Gap junction    Circadian entrainment    Glutamatergic synapse    Serotonergic synapse    Dopaminergic synapse    Long-term depression    Taste transduction    Insulin secretion    GnRH signaling pathway    Ovarian steroidogenesis    Estrogen signaling pathway    Melanogenesis    Thyroid hormone synthesis    Endocrine and other factor-regulated calcium reabsorption    Vasopressin-regulated water reabsorption    Salivary secretion    Gastric acid secretion    Pancreatic secretion    Bile secretion    Cocaine addiction    Amphetamine addiction    Morphine addiction    Alcoholism    Vibrio cholerae infection    Chagas disease (American trypanosomiasis)    Amoebiasis    Dilated cardiomyopathy   
REACTOMEQ5JWF2 [protein]
REACTOME PathwaysR-HSA-5610787 [pathway]   
NDEx NetworkGNAS
Atlas of Cancer Signalling NetworkGNAS
Wikipedia pathwaysGNAS
Orthology - Evolution
GeneTree (enSembl)ENSG00000087460
Phylogenetic Trees/Animal Genes : TreeFamGNAS
Homologs : HomoloGeneGNAS
Homology/Alignments : Family Browser (UCSC)GNAS
Gene fusions - Rearrangements
Fusion : MitelmanACTB::GNAS [7p22.1/20q13.32]  
Fusion : QuiverGNAS
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGNAS [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GNAS
Exome Variant ServerGNAS
GNOMAD BrowserENSG00000087460
Varsome BrowserGNAS
ACMGGNAS variants
Genomic Variants (DGV)GNAS [DGVbeta]
DECIPHERGNAS [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGNAS 
ICGC Data PortalGNAS 
TCGA Data PortalGNAS 
Broad Tumor PortalGNAS
OASIS PortalGNAS [ Somatic mutations - Copy number]
Cancer Gene: CensusGNAS 
Somatic Mutations in Cancer : COSMICGNAS  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DGNAS
Mutations and Diseases : HGMDGNAS
intOGen PortalGNAS
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)GNAS
DoCM (Curated mutations)GNAS
CIViC (Clinical Interpretations of Variants in Cancer)GNAS
NCG (London)GNAS
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM103580    139320    166350    174800    219080    603233    612462    612463    617686   
Orphanet279    18374    2516    12218    12219    11471    11470    11469    12558   
Genetic Testing Registry GNAS
NextProtQ5JWF2 [Medical]
Target ValidationGNAS
Huge Navigator GNAS [HugePedia]
ClinGenGNAS (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTDGNAS
Pharm GKB GenePA175
Pharm GKB PathwaysPA152530845   PA154444041   PA161749006   PA2024   
Drug Sensitivity GNAS
Clinical trialGNAS
DataMed IndexGNAS
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

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