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

Gene: GNAS-AS1

Alternate names for this Gene: GNAS-AS|GNAS1AS|GNASAS|NCRNA00075|NESP-AS|NESPAS|SANG

Gene Summary: This gene produces a paternally-imprinted antisense RNA transcript that helps regulate the GNAS complex locus, which encodes the alpha subunit of the stimulatory G protein. Defects in this gene are a cause of pseudohypoparathyroidism type Ib.

Gene is located in Chromosome: 20

Location in Chromosome : 20q13.32

Description of this Gene: GNAS antisense RNA 1

Type of Gene: ncRNA

rs1555868362 in GNAS;GNAS-AS1 gene and Dysmorphic features 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 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 27431290 2017 Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

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

PMID 8383205 1993 Imprinting in Albright's hereditary osteodystrophy.

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

rs3761263 in GNAS;GNAS-AS1 gene and Leukemia, Myelocytic, Acute PMID 27903959 2017 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.

rs79067846 in GNAS;GNAS-AS1 gene and Platelet Component Distribution Width Measurement PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.