GNAS

Summary

Gene Symbol: GNAS
Description: GNAS complex locus
Alias: AHO, C20orf45, GNAS1, GPSA, GSA, GSP, NESP, PITA3, POH, SCG6, SgVI, protein ALEX, protein GNAS, protein SCG6 (secretogranin VI), G protein subunit alpha S, adenylate cyclase-stimulating G alpha protein, alternative gene product encoded by XL-exon, extra large alphas protein, guanine nucleotide binding protein (G protein), alpha stimulating activity polypeptide 1, guanine nucleotide regulatory protein, guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas, neuroendocrine secretory protein, secretogranin VI
Species: human
Products:     GNAS

Top Publications

  1. Klagge A, Jessnitzer B, Pfaeffle R, Stumvoll M, Fuhrer D. A novel GNAS1 mutation in a German family with Albright's hereditary osteodystrophy. Exp Clin Endocrinol Diabetes. 2010;118:586-90 pubmed publisher
    ..is an inherited disorder and results from heterozygous loss of function mutation within the human G (s)? gene (GNAS1). AHO appears in two phenotypes, that may occur within the same family...
  2. Klemke M, Kehlenbach R, Huttner W. Two overlapping reading frames in a single exon encode interacting proteins--a novel way of gene usage. EMBO J. 2001;20:3849-60 pubmed
    ..Remarkably, ALEX binds to the XL-domain of XLalphas. Our results reveal a mechanism of gene usage that is without precedent in mammalian genomes. ..
  3. Eisenhardt A, Scherag A, Jockel K, Reis H, Rubben H, Siffert W. Lack of association of the genotype in the GNAS Fok I polymorphism and prostate cancer. Urol Int. 2011;87:80-6 pubmed publisher
    ..The G?s subunit has been considered as an apoptosis factor. In this study the role of GNAS T393C genotypes of the GNAS gene encoding G?s was analyzed for its influence on the development and progression of ..
  4. Landis C, Masters S, Spada A, Pace A, Bourne H, Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989;340:692-6 pubmed
    ..Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP...
  5. de Sanctis L, Vai S, Andreo M, Romagnolo D, Silvestro L, de Sanctis C. Brachydactyly in 14 genetically characterized pseudohypoparathyroidism type Ia patients. J Clin Endocrinol Metab. 2004;89:1650-5 pubmed
    ..a peculiar phenotype reported in subjects with pseudohypoparathyroidism type Ia (PHP-Ia) caused by mutations in the GNAS gene, which encodes for the alpha-subunit of the stimulatory G protein (Gsalpha)...
  6. Fragoso M, Latronico A, Carvalho F, Zerbini M, Marcondes J, Araujo L, et al. Activating mutation of the stimulatory G protein (gsp) as a putative cause of ovarian and testicular human stromal Leydig cell tumors. J Clin Endocrinol Metab. 1998;83:2074-8 pubmed
    ..Other activating mutations of the alpha-subunit of the Gs (gsp) have been identified in GH-secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and all ..
  7. Kacerovska D, Nemcova J, Pomahacova R, Michal M, Kazakov D. Cutaneous and superficial soft tissue lesions associated with Albright hereditary osteodystrophy: clinicopathological and molecular genetic study of 4 cases, including a novel mutation of the GNAS gene. Am J Dermatopathol. 2008;30:417-24 pubmed publisher
    ..One osteoma and the calcifying aponeurotic fibroma-like lesion were analyzed by HUMARA and proved to be clonal. In a family, a novel mutation in the GNAS gene was also identified.
  8. Faust R, Shore E, Stevens C, Xu M, Shah S, Phillips C, et al. Progressive osseous heteroplasia in the face of a child. Am J Med Genet A. 2003;118A:71-5 pubmed
    ..Analysis of DNA from peripheral blood leukocytes showed mutations in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase (GNAS1), confirming the diagnosis of progressive osseous heteroplasia.
  9. Jakobsen A, Ahlman H, Kolby L, Abrahamsson J, Fischer Colbrie R, Nilsson O. NESP55, a novel chromogranin-like peptide, is expressed in endocrine tumours of the pancreas and adrenal medulla but not in ileal carcinoids. Br J Cancer. 2003;88:1746-54 pubmed
    b>Neuroendocrine secretory protein 55, NESP55, is an acidic protein belonging to the chromogranin family. The distribution of NESP55 in human tumours is not known...

More Information

Publications107 found, 100 shown here

  1. Furukawa T, Kuboki Y, Tanji E, Yoshida S, Hatori T, Yamamoto M, et al. Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep. 2011;1:161 pubmed publisher
    ..uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF...
  2. Zheng H, Radeva G, McCann J, Hendy G, Goodyer C. Galphas transcripts are biallelically expressed in the human kidney cortex: implications for pseudohypoparathyroidism type 1b. J Clin Endocrinol Metab. 2001;86:4627-9 pubmed
    ..These data implicate abnormal imprinting of alternative regions within the GNAS1 locus as a more likely cause of pseudohypoparathyroid type 1b.
  3. Freson K, Jaeken J, Van Helvoirt M, de Zegher F, Wittevrongel C, Thys C, et al. Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation. Hum Mol Genet. 2003;12:1121-30 pubmed
    ..Both phenomena contribute to increased Gs signaling in patients with platelet hypersensitivity towards Gs-agonists and may be accompanied by neurological problems or growth deficiency. ..
  4. Jan de Beur S, Ding C, Germain Lee E, Cho J, Maret A, Levine M. Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1. Am J Hum Genet. 2003;73:314-22 pubmed
    ..molecular basis of pseudohypoparathyroidism type 1b (PHP type 1b) remains unknown, a defect in imprinting at the GNAS1 locus has been suggested by the consistent finding of paternal-specific patterns of DNA methylation on maternally ..
  5. Frey U, Alakus H, Wohlschlaeger J, Schmitz K, Winde G, van Calker H, et al. GNAS1 T393C polymorphism and survival in patients with sporadic colorectal cancer. Clin Cancer Res. 2005;11:5071-7 pubmed
    ..We have recently shown an association between the GNAS1 T393C polymorphism and disease progression in patients with bladder cancer with homozygous TT genotypes displaying ..
  6. Warner D, Gejman P, Collins R, Weinstein L. A novel mutation adjacent to the switch III domain of G(S alpha) in a patient with pseudohypoparathyroidism. Mol Endocrinol. 1997;11:1718-27 pubmed
    ..It is therefore possible that substitution or deletion of this residue may alter guanine nucleotide binding, which could lead to thermolability and impaired function. ..
  7. Mantovani G, Maghnie M, Weber G, De Menis E, Brunelli V, Cappa M, et al. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene. J Clin Endocrinol Metab. 2003;88:4070-4 pubmed
    ..In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary...
  8. Frey U, Lümmen G, Jager T, Jöckel K, Schmid K, Rubben H, et al. The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma. Clin Cancer Res. 2006;12:759-63 pubmed
    ..We have recently shown that TT genotypes of the GNAS1 T393C polymorphism display increased transcription of Galphas and a more favorable clinical course in bladder and ..
  9. Jan De Beur S, O Connell J, Peila R, Cho J, Deng Z, Kam S, et al. The pseudohypoparathyroidism type lb locus is linked to a region including GNAS1 at 20q13.3. J Bone Miner Res. 2003;18:424-33 pubmed
    ..osteodystrophy (AHO) and exhibit resistance to additional hormones because of heterozygous mutations in the GNAS1 gene that lead to a generalized deficiency of the a subunit of Gs, the heterotrimeric G protein that couples ..
  10. Palos Paz F, Perez Guerra O, Cameselle Teijeiro J, Rueda Chimeno C, Barreiro Morandeira F, Lado Abeal J, et al. Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain. Eur J Endocrinol. 2008;159:623-31 pubmed publisher
    ..in the TSH receptor (TSHR) gene, and less frequently in the adenylate cyclase-stimulating G alpha protein (GNAS) gene, are well established causes of TA in Europe...
  11. Kanda M, Knight S, Topazian M, Syngal S, Farrell J, Lee J, et al. Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts. Gut. 2013;62:1024-33 pubmed publisher
    ..Better approaches are needed to characterise these lesions. In this study we evaluated the utility of detecting mutant DNA in secretin-stimulated pancreatic juice...
  12. Liu J, Youn H, Yang J, Du N, Liu J, Liu H, et al. G-protein alpha-s and -12 subunits are involved in androgen-stimulated PI3K activation and androgen receptor transactivation in prostate cancer cells. Prostate. 2011;71:1276-86 pubmed publisher
    ..These data suggest that caveolae-associated G-protein alpha subunits are involved in AR transactivation by modulating the activities of different PI3K isoforms. ..
  13. Hayward B, Moran V, Strain L, Bonthron D. Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins. Proc Natl Acad Sci U S A. 1998;95:15475-80 pubmed
    ..The more 5' of these exons encodes the neuroendocrine secretory protein NESP55, which is expressed exclusively from the maternal allele...
  14. Nishikawa G, Sekine S, Ogawa R, Matsubara A, Mori T, Taniguchi H, et al. Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. Br J Cancer. 2013;108:951-8 pubmed publisher
    ..Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line...
  15. Swaroop A, Agarwal N, Gruen J, Bick D, Weissman S. Differential expression of novel Gs alpha signal transduction protein cDNA species. Nucleic Acids Res. 1991;19:4725-9 pubmed
    ..Differential expression of alternatively spliced Gs alpha species suggests novel signal transducing pathways. ..
  16. Weinstein L, Gejman P, Friedman E, Kadowaki T, Collins R, Gershon E, et al. Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A. 1990;87:8287-90 pubmed
  17. Mantovani G, Ballare E, Giammona E, Beck Peccoz P, Spada A. The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads. J Clin Endocrinol Metab. 2002;87:4736-40 pubmed
    ..The parental origin of Gs alpha was assessed by evaluating neuroendocrine secretory protein 55 and extra large alphas-like protein transcripts, which have been shown to be monoallelically and ..
  18. Abramowitz J, Grenet D, Birnbaumer M, Torres H, Birnbaumer L. XLalphas, the extra-long form of the alpha-subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex. Proc Natl Acad Sci U S A. 2004;101:8366-71 pubmed
    ..XXLb proteins are likely to be found as stable dimers with AlexX. The N-terminally longer proteins may play regulatory roles. ..
  19. Bray P, Carter A, Simons C, Guo V, Puckett C, Kamholz J, et al. Human cDNA clones for four species of G alpha s signal transduction protein. Proc Natl Acad Sci U S A. 1986;83:8893-7 pubmed
    ..S1 nuclease protection experiments revealed at least two forms of alpha s mRNA. A mechanism for generating four species of alpha s mRNA by alternative splicing of precursor RNA is proposed. ..
  20. Hayward B, Kamiya M, Strain L, Moran V, Campbell R, Hayashizaki Y, et al. The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proc Natl Acad Sci U S A. 1998;95:10038-43 pubmed
    The GNAS1 gene encodes the alpha subunit of the G protein Gs, which couples receptor binding by several hormones to activation of adenylate cyclase...
  21. Frey U, Nuckel H, Sellmann L, Siemer D, Kuppers R, Dürig J, et al. The GNAS1 T393C polymorphism is associated with disease progression and survival in chronic lymphocytic leukemia. Clin Cancer Res. 2006;12:5686-92 pubmed
    ..The TT genotype of the GNAS1 T393C polymorphism is associated with increased Galphas transcript levels and a more favorable clinical course in ..
  22. Michienzi S, Cherman N, Holmbeck K, Funari A, Collins M, Bianco P, et al. GNAS transcripts in skeletal progenitors: evidence for random asymmetric allelic expression of Gs alpha. Hum Mol Genet. 2007;16:1921-30 pubmed
    Activating mutations of the Gsalpha gene, encoded by the guanine nucleotide-binding protein, alpha stimulating (GNAS) locus located on chromosome 20q13, underlie different clinical phenotypes characterized by skeletal lesions [fibrous ..
  23. Harris B. Complete cDNA sequence of a human stimulatory GTP-binding protein alpha subunit. Nucleic Acids Res. 1988;16:3585 pubmed
  24. Levine M, Modi W, O Brien S. Mapping of the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase (GNAS1) to 20q13.2----q13.3 in human by in situ hybridization. Genomics. 1991;11:478-9 pubmed
  25. de Sanctis L, Romagnolo D, Olivero M, Buzi F, Maghnie M, Scirè G, et al. Molecular analysis of the GNAS1 gene for the correct diagnosis of Albright hereditary osteodystrophy and pseudohypoparathyroidism. Pediatr Res. 2003;53:749-55 pubmed
    ..Heterozygous mutations in the GNAS1 gene encoding the Gsalpha protein have been identified both in PHP-Ia and in pseudopseudohypoparathyroidism (PPHP),..
  26. Bastepe M, Juppner H. GNAS locus and pseudohypoparathyroidism. Horm Res. 2005;63:65-74 pubmed
    ..Most of these PHP forms are caused by defects in GNAS (20q13.3), an imprinted gene locus with multiple transcriptional units...
  27. Castellone M, Teramoto H, Williams B, Druey K, Gutkind J. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310:1504-10 pubmed
    ..These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer. ..
  28. Wilson C, McIntyre R, Arends M, Adams D. The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways. Oncogene. 2010;29:4567-75 pubmed publisher
    Somatically acquired, activating mutations of GNAS, the gene encoding the stimulatory G-protein Gsalpha subunit, have been identified in kidney, thyroid, pituitary, leydig cell, adrenocortical and, more recently, in colorectal tumours, ..
  29. Schwindinger W, Miric A, Zimmerman D, Levine M. A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy uncouples cell surface receptors from adenylyl cyclase. J Biol Chem. 1994;269:25387-91 pubmed
    Albright hereditary osteodystrophy (AHO) is an autosomal-dominant disorder characterized by decreased expression of Gs alpha and widespread tissue resistance to hormones that activate adenylyl cyclase...
  30. Klemke M, Pasolli H, Kehlenbach R, Offermanns S, Schultz G, Huttner W. Characterization of the extra-large G protein alpha-subunit XLalphas. II. Signal transduction properties. J Biol Chem. 2000;275:33633-40 pubmed
    ..Our results suggest that in neuroendocrine cells, the two related G proteins, Galphas and XLalphas, exhibit distinct properties with regard to receptor-mediated activation but converge onto the same effector system, adenylyl cyclase. ..
  31. Mantovani G, de Sanctis L, Barbieri A, Elli F, Bollati V, Vaira V, et al. Pseudohypoparathyroidism and GNAS epigenetic defects: clinical evaluation of albright hereditary osteodystrophy and molecular analysis in 40 patients. J Clin Endocrinol Metab. 2010;95:651-8 pubmed publisher
    The two main subtypes of pseudohypoparathyroidism (PHP), PHP-Ia and -Ib, are caused by mutations in GNAS exons 1-13 and methylation defects in the imprinted GNAS cluster, respectively...
  32. Richard N, Abeguilé G, Coudray N, Mittre H, Gruchy N, Andrieux J, et al. A new deletion ablating NESP55 causes loss of maternal imprint of A/B GNAS and autosomal dominant pseudohypoparathyroidism type Ib. J Clin Endocrinol Metab. 2012;97:E863-7 pubmed publisher
    ..They can be either coding [G?s, XL?s, and neuroendocrine secretory protein-55 (NESP55)] or nontranslated (A/B and AS). The paternal AS transcript lies antisense to nesp55.
  33. Weinstein L, Shenker A, Gejman P, Merino M, Friedman E, Spiegel A. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med. 1991;325:1688-95 pubmed
    ..We analyzed DNA from tissues of patients with the McCune-Albright syndrome for the presence of activating mutations of the gene for the alpha subunit of the G protein (Gs alpha) that stimulates cAMP formation...
  34. Schmitz K, Lang H, Frey U, Sotiropoulos G, Wohlschlaeger J, Reis H, et al. GNAS1 T393C polymorphism is associated with clinical course in patients with intrahepatic cholangiocarcinoma. Neoplasia. 2007;9:159-65 pubmed
    The GNAS1 locus encodes the Galphas protein, which stimulates the formation of cyclo-adenosinemonophosphate (cAMP). The cAMP pathway mediates pleiotropic effects, including the regulation of apoptosis and proliferation...
  35. Fernandez Rebollo E, Garcia Cuartero B, Garin I, Largo C, Martinez F, Garcia Lacalle C, et al. Intragenic GNAS deletion involving exon A/B in pseudohypoparathyroidism type 1A resulting in an apparent loss of exon A/B methylation: potential for misdiagnosis of pseudohypoparathyroidism type 1B. J Clin Endocrinol Metab. 2010;95:765-71 pubmed publisher
    ..Mutations affecting G(s)alpha coding exons of GNAS and epigenetic alterations in the same gene are associated with PHP-Ia and -Ib, respectively...
  36. Ideno N, Ohtsuka T, Kono H, Fujiwara K, Oda Y, Aishima S, et al. Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype. Ann Surg. 2013;258:141-51 pubmed publisher
    ..Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types...
  37. Shore E, Ahn J, Jan de Beur S, Li M, Xu M, Gardner R, et al. Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med. 2002;346:99-106 pubmed
    ..AHO is caused by heterozygous inactivating mutations in the GNAS1 gene that result in decreased expression or function of the alpha subunit of the stimulatory G protein (Gsalpha) ..
  38. Frey U, Eisenhardt A, Lümmen G, Rubben H, Jöckel K, Schmid K, et al. The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:871-7 pubmed
    The G protein G(alpha)s pathway is linked to proapoptotic signaling in cancer cell lines. To assess the role of the GNAS1 locus encoding G(alpha)s as a genetic factor for disease progression of transitional cell carcinoma (TCC) of the ..
  39. Klenke S, Siffert W, Frey U. A novel aspect of GNAS imprinting: higher maternal expression of G?s in human lymphoblasts, peripheral blood mononuclear cells, mammary adipose tissue, and heart. Mol Cell Endocrinol. 2011;341:63-70 pubmed publisher
    The human GNAS gene is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in pituitary, thyroid, renal proximal tubules, and gonads, but is supposed to be biallelically expressed with an equal ..
  40. Turan S, Bastepe M. The GNAS complex locus and human diseases associated with loss-of-function mutations or epimutations within this imprinted gene. Horm Res Paediatr. 2013;80:229-41 pubmed publisher
    b>GNAS is a complex imprinted locus leading to several different gene products that show exclusive monoallelic expression...
  41. Kehlenbach R, Matthey J, Huttner W. XL alpha s is a new type of G protein. Nature. 1994;372:804-9 pubmed
    ..Hence, XL alpha s may mediate the effects of cholera toxin on secretory vesicle formation. ..
  42. Ischia R, Lovisetti Scamihorn P, Hogue Angeletti R, Wolkersdorfer M, Winkler H, Fischer Colbrie R. Molecular cloning and characterization of NESP55, a novel chromogranin-like precursor of a peptide with 5-HT1B receptor antagonist activity. J Biol Chem. 1997;272:11657-62 pubmed
    ..We describe here the molecular characterization of NESP55 (neuroendocrine secretory protein of Mr 55,000), a novel member of the chromogranins...
  43. Warner D, Weng G, Yu S, Matalon R, Weinstein L. A novel mutation in the switch 3 region of Gsalpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation. J Biol Chem. 1998;273:23976-83 pubmed
    Albright hereditary osteodystrophy (AHO), a disorder characterized by skeletal abnormalities and obesity, is associated with heterozygous inactivating mutations in the gene for Gsalpha...
  44. Yu D, Yu S, Schuster V, Kruse K, Clericuzio C, Weinstein L. Identification of two novel deletion mutations within the Gs alpha gene (GNAS1) in Albright hereditary osteodystrophy. J Clin Endocrinol Metab. 1999;84:3254-9 pubmed
    ..cyclase stimulation, and in a number of cases heterozygous loss of function mutations within the Gs alpha gene (GNAS1) have been identified...
  45. Freson K, Hoylaerts M, Jaeken J, Eyssen M, Arnout J, Vermylen J, et al. Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to Gs hyperfunction in platelets and is a risk factor for bleeding. Thromb Haemost. 2001;86:733-8 pubmed
    Alternatively spliced GNAS1 and XL-GNAS1, encoding respectively the stimulatory G-protein alpha-subunit (Gsalpha) and the extra-large stimulatory G-protein alpha-subunit (XLsalpha), are located on the imprinted chromosomal region 20q13...
  46. Germain Lee E, Ding C, Deng Z, Crane J, Saji M, Ringel M, et al. Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. Biochem Biophys Res Commun. 2002;296:67-72 pubmed
    Albright hereditary osteodystrophy (AHO) is characterized by multiple somatic defects secondary to mutations in the GNAS1 gene. AHO patients with mutations on maternally inherited alleles are resistant to multiple hormones (e.g...
  47. Chen C, Liu J, Cheng S, Chang F, Yuh Y. McCune-Albright syndrome associated with pituitary microadenoma: patient report. J Pediatr Endocrinol Metab. 2004;17:365-9 pubmed
    ..Ovarian cysts may be detected on pelvic ultrasound. Our patient was also found to have pituitary microadenoma, evidenced by dynamic magnetic resonance imaging. ..
  48. Plagge A, Kelsey G. Imprinting the Gnas locus. Cytogenet Genome Res. 2006;113:178-87 pubmed
    b>Gnas is an enigmatic and rather complex imprinted gene locus. A single transcription unit encodes three, and possibly more, distinct proteins...
  49. Taboada G, Tabet A, Naves L, de Carvalho D, Gadelha M. Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience. Pituitary. 2009;12:165-9 pubmed publisher
    ..Exons 8 and 9 (including codons 201 and 227, respectively) of the GNAS gene were amplified by polymerase chain reaction (PCR)...
  50. Crane J, Shamblott M, Axelman J, Hsu S, Levine M, Germain Lee E. Imprinting status of Galpha(s), NESP55, and XLalphas in cell cultures derived from human embryonic germ cells: GNAS imprinting in human embryonic germ cells. Clin Transl Sci. 2009;2:355-60 pubmed publisher
    b>GNAS is a complex gene that through use of alternative first exons encodes signaling proteins Galpha(s) and XLalphas plus neurosecretory protein NESP55...
  51. Maupetit Méhouas S, Mariot V, Reynès C, Bertrand G, Feillet F, Carel J, et al. Quantification of the methylation at the GNAS locus identifies subtypes of sporadic pseudohypoparathyroidism type Ib. J Med Genet. 2011;48:55-63 pubmed publisher
    Pseudohypoparathyroidism type Ib (PHP-Ib) is due to epigenetic changes at the imprinted GNAS locus, including loss of methylation at the A/B differentially methylated region (DMR) and sometimes at the XL and AS DMRs and gain of ..
  52. Zazo C, Thiele S, Martin C, Fernandez Rebollo E, Martinez Indart L, Werner R, et al. Gs? activity is reduced in erythrocyte membranes of patients with psedohypoparathyroidism due to epigenetic alterations at the GNAS locus. J Bone Miner Res. 2011;26:1864-70 pubmed publisher
    ..In PHP-Ia, inactivating mutations of the GNAS gene lead to haploinsufficiency in some tissues with biallelic expression, so in addition to PHP, Albright's ..
  53. Elli F, deSanctis L, Ceoloni B, Barbieri A, Bordogna P, Beck Peccoz P, et al. Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations. Hum Mutat. 2013;34:411-6 pubmed publisher
    ..parathyroid hormone due to partial deficiency of the ? subunit of the stimulatory G protein (Gs?), encoded by the GNAS gene...
  54. Molin M, Matthaei H, Wu J, Blackford A, Debeljak M, Rezaee N, et al. Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg Oncol. 2013;20:3802-8 pubmed publisher
    ..The recent identification of activating GNAS mutations at codon 201 in IPMNs is a promising target for early detection and therapy...
  55. Richard N, Molin A, Coudray N, Rault Guillaume P, Juppner H, Kottler M. Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and provide evidence for a role of XL?s in fetal development. J Clin Endocrinol Metab. 2013;98:E1549-56 pubmed publisher
    Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia (POH) when paternally inherited...
  56. Kozasa T, Itoh H, Tsukamoto T, Kaziro Y. Isolation and characterization of the human Gs alpha gene. Proc Natl Acad Sci U S A. 1988;85:2081-5 pubmed
    ..In the 5' flanking region, there are several blocks of sequences that are similar to the sequences of the 5' flanking region of the human c-Ki-ras2 gene. ..
  57. Campbell R, Gosden C, Bonthron D. Parental origin of transcription from the human GNAS1 gene. J Med Genet. 1994;31:607-14 pubmed
    ..hereditary osteodystrophy (AHO) determined by the parent of transmission, suggests that the human Gs alpha gene (GNAS1), in which mutations occur in AHO, may be under imprinted control...
  58. Iiri T, Herzmark P, Nakamoto J, Van Dop C, Bourne H. Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function. Nature. 1994;371:164-8 pubmed
    ..In vitro experiments indicate that accelerated release of GDP causes both the constitutive activity and the thermolability of alpha s-A366S. ..
  59. Ahmed S, Barr D, Bonthron D. GNAS1 mutations and progressive osseous heteroplasia. N Engl J Med. 2002;346:1669-71 pubmed
  60. Yang W, White B, Spicer E, Weinstein B, Hildebrandt J. Complex haplotype structure of the human GNAS gene identifies a recombination hotspot centred on a single nucleotide polymorphism widely used in association studies. Pharmacogenetics. 2004;14:741-7 pubmed
    ..The haplotype structure of the GNAS locus warrants reevaluation of previous association studies that used marker rs7121 and affects choice of SNP ..
  61. Mantovani G, Spada A. Mutations in the Gs alpha gene causing hormone resistance. Best Pract Res Clin Endocrinol Metab. 2006;20:501-13 pubmed
    ..change of G proteins so far unequivocally associated with endocrine disorders occurs in the Gsalpha gene (GNAS1, guanine nucleotide binding protein alpha stimulating activity polypeptide 1), which activates cyclic AMP (cAMP)-..
  62. Thiele S, de Sanctis L, Werner R, Grötzinger J, Aydin C, Juppner H, et al. Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gs?-receptor interaction. Hum Mutat. 2011;32:653-60 pubmed publisher
    Pseudohypoparathyroidism type Ia (PHPIa) is caused by GNAS mutations leading to deficiency of the ?-subunit of stimulatory G proteins (Gs?) that mediate signal transduction of G protein-coupled receptors via cAMP...
  63. Elli F, Barbieri A, Bordogna P, Ferrari P, Bufo R, Ferrante E, et al. Screening for GNAS genetic and epigenetic alterations in progressive osseous heteroplasia: first Italian series. Bone. 2013;56:276-80 pubmed publisher
    ..Most cases of POH are caused by paternally inherited inactivating mutations of GNAS gene...
  64. Tsai J, Yuan R, Chen Y, Liau J, Jeng Y. GNAS Is frequently mutated in a specific subgroup of intraductal papillary neoplasms of the bile duct. Am J Surg Pathol. 2013;37:1862-70 pubmed publisher
    ..Approximately two thirds of IPMNs have activating point mutations of GNAS at codon 201. The role of GNAS mutation is unclear in IPN-B...
  65. Sasaki M, Matsubara T, Nitta T, Sato Y, Nakanuma Y. GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct. PLoS ONE. 2013;8:e81706 pubmed publisher
    ..Although activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of IPMNs of the pancreas, there have been few studies ..
  66. Weiss U, Ischia R, Eder S, Lovisetti Scamihorn P, Bauer R, Fischer Colbrie R. Neuroendocrine secretory protein 55 (NESP55): alternative splicing onto transcripts of the GNAS gene and posttranslational processing of a maternally expressed protein. Neuroendocrinology. 2000;71:177-86 pubmed
    ..This locus encoded for the Neuroendocrine Secretory Protein with an apparent molecular weight of 55,000 (NESP55), which is transcribed exclusively from the ..
  67. Liu J, Nealon J, Weinstein L. Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB. Hum Mol Genet. 2005;14:95-102 pubmed
    Pseudohypoparathyroidism type IB (PHPIB) is associated with abnormal imprinting of GNAS, the gene encoding the heterotrimeric G protein Gsalpha and other alternative products...
  68. Linglart A, Mahon M, Kerachian M, Berlach D, Hendy G, Juppner H, et al. Coding GNAS mutations leading to hormone resistance impair in vitro agonist- and cholera toxin-induced adenosine cyclic 3',5'-monophosphate formation mediated by human XLalphas. Endocrinology. 2006;147:2253-62 pubmed
    Most loss of function mutations of GNAS identified in different forms of pseudohypoparathyroidism disrupt not only the stimulatory G protein alpha-subunit (Gsalpha), but also its paternally expressed variant, XLalphas...
  69. Long D, McGuire S, Levine M, Weinstein L, Germain Lee E. Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab. 2007;92:1073-9 pubmed
    Obesity is a prominent feature of Albright hereditary osteodystrophy (AHO), a disorder caused by heterozygous GNAS mutations that disrupt the stimulatory G protein alpha-subunit Galpha(s)...
  70. Lee S, Jeong E, Soung Y, Lee J, Yoo N, Lee S. Absence of GNAS and EGFL6 mutations in common human cancers. Pathology. 2008;40:95-7 pubmed
  71. Adegbite N, Xu M, Kaplan F, Shore E, Pignolo R. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A. 2008;146A:1788-96 pubmed publisher
    ..hereditary osteodystrophy (AHO) or hormone resistance, clinical manifestations that are also associated with GNAS inactivation...
  72. Lebrun M, Richard N, Abeguile G, David A, Coeslier Dieux A, Journel H, et al. Progressive osseous heteroplasia: a model for the imprinting effects of GNAS inactivating mutations in humans. J Clin Endocrinol Metab. 2010;95:3028-38 pubmed publisher
    Heterozygous GNAS inactivating mutations are known to induce pseudohypoparathyroidism type 1a when maternally inherited and pseudopseudohypoparathyroidism when paternally inherited...
  73. Fernandez Rebollo E, Perez de Nanclares G, Lecumberri B, Turan S, Anda E, Pérez Nanclares G, et al. Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib?. J Bone Miner Res. 2011;26:1854-63 pubmed publisher
    ..dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B...
  74. Nault J, Fabre M, Couchy G, Pilati C, Jeannot E, Tran Van Nhieu J, et al. GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation. J Hepatol. 2012;56:184-91 pubmed publisher
    Mosaic G-protein alpha-subunit (GNAS)-activating mutations are responsible for the McCune-Albright (MCA) syndrome...
  75. Hsu M, Sasaki M, Igarashi S, Sato Y, Nakanuma Y. KRAS and GNAS mutations and p53 overexpression in biliary intraepithelial neoplasia and intrahepatic cholangiocarcinomas. Cancer. 2013;119:1669-74 pubmed publisher
    ..this study, the authors investigated the status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) mutations and tumor protein 53 (p53) overexpression in the stepwise process of ..
  76. Regard J, Malhotra D, Gvozdenovic Jeremic J, Josey M, Chen M, Weinstein L, et al. Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med. 2013;19:1505-12 pubmed publisher
    ..In progressive osseous heteroplasia, a human disease caused by null mutations in GNAS, which encodes Gαs, Hedgehog signaling is upregulated in ectopic osteoblasts and progenitor cells...
  77. Elli F, de Sanctis L, Bollati V, Tarantini L, Filopanti M, Barbieri A, et al. Quantitative analysis of methylation defects and correlation with clinical characteristics in patients with pseudohypoparathyroidism type I and GNAS epigenetic alterations. J Clin Endocrinol Metab. 2014;99:E508-17 pubmed publisher
    ..G protein (Gs?) exons 1-13, encoded by the guanine nucleotide binding-protein ?-stimulating activity polypeptide 1 (GNAS), whereas the majority of PHP-Ib patients, who classically display hormone resistance limited to PTH and TSH with ..
  78. Schwindinger W, Francomano C, Levine M. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci U S A. 1992;89:5152-6 pubmed
    ..Further, these results suggest that the molecular basis of MAS is a postzygotic mutation in Gs alpha that causes constitutive activation of adenylyl cyclase...
  79. Pohlenz J, Ahrens W, Hiort O. A new heterozygous mutation (L338N) in the human Gsalpha (GNAS1) gene as a cause for congenital hypothyroidism in Albright's hereditary osteodystrophy. Eur J Endocrinol. 2003;148:463-8 pubmed
    ..DNA analysis detected a new heterozygous mutation (L338N) in the Gsalpha protein (GNAS1) gene...
  80. Bastepe M, Fröhlich L, Linglart A, Abu Zahra H, Tojo K, Ward L, et al. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nat Genet. 2005;37:25-7 pubmed
    Epigenetic defects in the imprinted GNAS cluster are associated with pseudohypoparathyroidism type Ib...
  81. Freson K, Izzi B, Labarque V, Van Helvoirt M, Thys C, Wittevrongel C, et al. GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets. J Clin Endocrinol Metab. 2008;93:4851-9 pubmed publisher
    b>GNAS is an imprinted region that gives rise to several transcripts, antisense transcripts, and noncoding RNAs, including transcription of RNA encoding the alpha-subunit of the stimulatory G protein (Gsalpha)...
  82. Choi Y, Kim S, Oh J, Juhnn Y. Stimulatory heterotrimeric G protein augments gamma ray-induced apoptosis by up-regulation of Bak expression via CREB and AP-1 in H1299 human lung cancer cells. Exp Mol Med. 2009;41:592-600 pubmed publisher
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    Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas...
  84. Fernandez Rebollo E, Lecumberri B, Gaztambide S, Martinez Indart L, Perez de Nanclares G, Castano L. Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients with pseudohypoparathyroidism. J Clin Endocrinol Metab. 2013;98:E996-1006 pubmed publisher
  85. Weinstein L, Gejman P, De Mazancourt P, American N, Spiegel A. A heterozygous 4-bp deletion mutation in the Gs alpha gene (GNAS1) in a patient with Albright hereditary osteodystrophy. Genomics. 1992;13:1319-21 pubmed
    Several heterozygous mutations within the gene encoding the alpha-subunit of Gs (GNAS1), the G protein that stimulates adenylyl cyclase, have been previously identified in patients with Albright hereditary osteodystrophy (AHO)...
  86. Freda P, Chung W, Matsuoka N, Walsh J, Kanibir M, Kleinman G, et al. Analysis of GNAS mutations in 60 growth hormone secreting pituitary tumors: correlation with clinical and pathological characteristics and surgical outcome based on highly sensitive GH and IGF-I criteria for remission. Pituitary. 2007;10:275-82 pubmed
    ..pituitary tumor formation are not well understood, mutations in the alpha-subunit of the stimulatory G gene, GNAS, have been identified in up to 40%...
  87. Mariot V, WU J, Aydin C, Mantovani G, Mahon M, Linglart A, et al. Potent constitutive cyclic AMP-generating activity of XL?s implicates this imprinted GNAS product in the pathogenesis of McCune-Albright syndrome and fibrous dysplasia of bone. Bone. 2011;48:312-20 pubmed publisher
    ..skin lesions, precocious puberty, and fibrous dyslasia of bone, carry postzygotic heterozygous mutations of GNAS causing constitutive cAMP signaling...
  88. Yamada M, Sekine S, Ogawa R, Taniguchi H, Kushima R, Tsuda H, et al. Frequent activating GNAS mutations in villous adenoma of the colorectum. J Pathol. 2012;228:113-8 pubmed publisher
    To elucidate the role of GNAS mutations in colorectal tumourigenesis, we performed a mutation analysis in a total of 234 colorectal tumours, including adenomas, serrated lesions and adenocarcinomas...
  89. Patten J, Johns D, Valle D, Eil C, Gruppuso P, Steele G, et al. Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. N Engl J Med. 1990;322:1412-9 pubmed
    ..We conclude that in at least some patients with Albright's hereditary osteodystrophy, the disease is caused by a single-base substitution in the Gs alpha gene and is thus due to an inherited mutation in a human G protein...
  90. Ahmed S, Dixon P, Bonthron D, Stirling H, Barr D, Kelnar C, et al. GNAS1 mutational analysis in pseudohypoparathyroidism. Clin Endocrinol (Oxf). 1998;49:525-31 pubmed
    Mutations of the GNAS1 gene, which is located on chromosome 20q13...
  91. Hayward B, Bonthron D. An imprinted antisense transcript at the human GNAS1 locus. Hum Mol Genet. 2000;9:835-41 pubmed
    ..The most 5' of these is maternally expressed, and encodes neuroendocrine secretory protein 55 (NESP55), whose coding region does not overlap with that of G(s)alpha...
  92. Ahrens W, Hiort O, Staedt P, Kirschner T, Marschke C, Kruse K. Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy. J Clin Endocrinol Metab. 2001;86:4630-4 pubmed
    ..Different inactivating mutations of the gene GNAS1 encoding Gsalpha lead to a reduced Gsalpha protein activity in patients with AHO and pseudohypoparathyroidism type ..