Gene: GNAS

Alternate names for this Gene: AHO|C20orf45|GNAS1|GPSA|GSA|GSP|NESP|PITA3|POH|SCG6|SgVI

Gene Summary: This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript is produced from an overlapping locus on the opposite strand. One of the transcripts produced from this locus, and the antisense transcript, are paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein - Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene result in pseudohypoparathyroidism type 1a, pseudohypoparathyroidism type 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors.

Gene is located in Chromosome: 20

Location in Chromosome : 20q13.32

Description of this Gene: GNAS complex locus

Type of Gene: protein-coding

rs121913495 in GNAS gene and Acth-Independent Macronodular Adrenal Hyperplasia PMID 12727968 2003 Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene.

rs13831 in GNAS gene and Adenocarcinoma of large intestine PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs11554273 in GNAS gene and Adenocarcinoma of lung (disorder) PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs11554273 in GNAS gene and Adenocarcinoma of pancreas PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs11554273 in GNAS gene and Adrenocortical carcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs6026580 in GNAS gene and Blood urea nitrogen measurement PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.

PMID 22797727 2012 Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

rs185799410 in GNAS gene and Body Height PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 31562340 2019 Characterizing rare and low-frequency height-associated variants in the Japanese population.

rs13831 in GNAS gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 1 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs13831 in GNAS gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 10 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs13831 in GNAS gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 12 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs13831 in GNAS gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 3 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs13831 in GNAS gene and Colorectal Carcinoma PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs11554273 in GNAS gene and Colorectal Neoplasms PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs11554266 in GNAS gene and Creatinine measurement, serum (procedure) PMID 29124443 2018 Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.

rs11554273 in GNAS gene and Cutaneous Melanoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1407040 in GNAS gene and Diastolic blood pressure PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs76801208 in GNAS gene and Drug-induced neutropenia PMID 28762467 2018 Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.

rs1555891562 in GNAS gene and Dysmorphic features PMID 8383205 1993 Imprinting in Albright's hereditary osteodystrophy.

PMID 23281139 2013 Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations.

PMID 23884777 2013 Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and provide evidence for a role of XLαs in fetal development.

PMID 25802881 2015 A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.

PMID 17161328 2006 Mutations in the Gs alpha gene causing hormone resistance.

PMID 27431290 2017 Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

PMID 11600516 2001 Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy.

PMID 14561710 2003 Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS.

PMID 18796523 2008 Compound heterozygous mutations in the GNAS gene of a boy with morbid obesity, thyroid-stimulating hormone resistance, pseudohypoparathyroidism, and a prothrombotic state.

PMID 10980525 2000 Activating and inactivating mutations in the human GNAS1 gene.

rs11554273 in GNAS gene and Gastric Adenocarcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs11554266 in GNAS gene and Glomerular Filtration Rate PMID 29124443 2018 Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.

PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.

PMID 31015462 2019 Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis.

rs11554266 in GNAS gene and Hyperuricemia PMID 29124443 2018 Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.

rs11554273 in GNAS gene and Liver carcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs13831 in GNAS gene and Malignant neoplasm of large intestine PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs13831 in GNAS gene and Malignant tumor of colon PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs11554273 in GNAS gene and Mammary Neoplasms PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs11554273 in GNAS gene and McCune-Albright Syndrome PMID 23536913 2013 Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing.

PMID 15126527 2004 Activating Gsalpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome--a European Collaborative Study.

PMID 17493233 2007 A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone.

PMID 1944469 1991 Activating mutations of the stimulatory G protein in the McCune-Albright syndrome.

PMID 7751320 1995 Overexpression of Gs alpha subunit in thyroid tumors bearing a mutated Gs alpha gene.

PMID 1594625 1992 Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome.

PMID 10571700 1999 A novel GNAS1 mutation, R201G, in McCune-albright syndrome.

PMID 11029463 2001 Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of G alpha(s). A cause of pseudohypoparathyroidism type Ib.

PMID 8699958 1996 Clinical implications of genetic defects in G proteins. The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy.

rs1407040 in GNAS gene and Mean blood pressure PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs1555891562 in GNAS gene and Multiple congenital anomalies PMID 11600516 2001 Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy.

PMID 14561710 2003 Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS.

PMID 10980525 2000 Activating and inactivating mutations in the human GNAS1 gene.

PMID 17161328 2006 Mutations in the Gs alpha gene causing hormone resistance.

PMID 27431290 2017 Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

PMID 8383205 1993 Imprinting in Albright's hereditary osteodystrophy.

PMID 25802881 2015 A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.

PMID 23281139 2013 Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations.

PMID 23884777 2013 Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and provide evidence for a role of XLαs in fetal development.

PMID 18796523 2008 Compound heterozygous mutations in the GNAS gene of a boy with morbid obesity, thyroid-stimulating hormone resistance, pseudohypoparathyroidism, and a prothrombotic state.

rs11554273 in GNAS gene and Neoplasms PMID 21835143 2012 GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

rs587776829 in GNAS gene and Osteoma cutis PMID 25219572 2015 GNAS mutations in Pseudohypoparathyroidism type 1a and related disorders.

PMID 23796510 2013 Screening for GNAS genetic and epigenetic alterations in progressive osseous heteroplasia: first Italian series.

rs1555891562 in GNAS gene and Overgrowth PMID 8383205 1993 Imprinting in Albright's hereditary osteodystrophy.

PMID 27431290 2017 Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

PMID 17161328 2006 Mutations in the Gs alpha gene causing hormone resistance.

PMID 25802881 2015 A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.

PMID 23884777 2013 Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and provide evidence for a role of XLαs in fetal development.

PMID 11600516 2001 Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy.

PMID 18796523 2008 Compound heterozygous mutations in the GNAS gene of a boy with morbid obesity, thyroid-stimulating hormone resistance, pseudohypoparathyroidism, and a prothrombotic state.

PMID 10980525 2000 Activating and inactivating mutations in the human GNAS1 gene.

PMID 23281139 2013 Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations.

PMID 14561710 2003 Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS.

rs397514456 in GNAS gene and Pseudohypoparathyroidism Type 1C PMID 21488135 2011 Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα-receptor interaction.

rs137854531 in GNAS gene and Pseudohypoparathyroidism, Type Ia PMID 8702665 1996 Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation.

PMID 9159128 1997 Conditional activation defect of a human Gsalpha mutant.

PMID 11600516 2001 Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy.

PMID 9727013 1998 A novel mutation in the switch 3 region of Gsalpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation.

PMID 12624854 2003 Analysis of GNAS1 and overlapping transcripts identifies the parental origin of mutations in patients with sporadic Albright hereditary osteodystrophy and reveals a model system in which to observe the effects of splicing mutations on translated and untranslated messenger RNA.

PMID 9328353 1997 A novel mutation adjacent to the switch III domain of G(S alpha) in a patient with pseudohypoparathyroidism.

PMID 11450852 2001 Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia.

PMID 7523385 1994 A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy uncouples cell surface receptors from adenylyl cyclase.

PMID 8388883 1993 Heterogeneous mutations in the gene encoding the alpha-subunit of the stimulatory G protein of adenylyl cyclase in Albright hereditary osteodystrophy.

PMID 15817905 2005 Early manifestation of calcinosis cutis in pseudohypoparathyroidism type Ia associated with a novel mutation in the GNAS gene.

PMID 25802881 2015 A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.

PMID 21488135 2011 Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα-receptor interaction.

PMID 23533243 2013 Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients with pseudohypoparathyroidism.

PMID 11092390 2000 Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification.

PMID 26633545 2016 Molecular diagnostic experience of whole-exome sequencing in adult patients.

PMID 21525160 2011 Increased prevalence of carpal tunnel syndrome in albright hereditary osteodystrophy.

rs137854535 in GNAS gene and Pseudopseudohypoparathyroidism PMID 9727013 1998 A novel mutation in the switch 3 region of Gsalpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation.

PMID 25802881 2015 A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.

PMID 26633545 2016 Molecular diagnostic experience of whole-exome sequencing in adult patients.

PMID 23533243 2013 Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients with pseudohypoparathyroidism.

PMID 11092390 2000 Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification.

PMID 21525160 2011 Increased prevalence of carpal tunnel syndrome in albright hereditary osteodystrophy.

rs11554273 in GNAS gene and Squamous cell carcinoma of the head and neck PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs11554266 in GNAS gene and Uric acid measurement (procedure) PMID 29124443 2018 Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.

PMID 31578528 2019 Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

rs11554273 in GNAS gene and Uterine Cervical Neoplasm PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs117041046 in GNAS gene and response to bronchodilator PMID 26634245 2015 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.