GNAS complex locus

GNAS
Identifiers
Aliases	GNAS, AHO, C20orf45, GNAS1, GPSA, GSA, GSP, NESP, POH, SCG6, SgVI, GNAS complex locus
External IDs	OMIM: 139320 MGI: 95777 HomoloGene: 55534 GeneCards: GNAS
Gene ontology Molecular function • molecular function • nucleotide binding • G-protein beta/gamma-subunit complex binding • GTP binding • signal transducer activity • metal ion binding • protein binding • GTPase activity • guanyl nucleotide binding • insulin-like growth factor receptor binding • mu-type opioid receptor binding • corticotropin-releasing hormone receptor 1 binding • beta-2 adrenergic receptor binding • ionotropic glutamate receptor binding • D1 dopamine receptor binding Cellular component • cytoplasm • perinuclear region of cytoplasm • extracellular region • transport vesicle • cytoplasmic vesicle • nucleus • cytosol • trans-Golgi network membrane • membrane • plasma membrane • heterotrimeric G-protein complex • intrinsic component of membrane • extracellular exosome • ruffle • cell projection • dendrite Biological process • female pregnancy • negative regulation of multicellular organism growth • response to parathyroid hormone • protein secretion • hair follicle placode formation • positive regulation of cAMP biosynthetic process • cellular response to catecholamine stimulus • G-protein coupled receptor signaling pathway • adenylate cyclase-activating dopamine receptor signaling pathway • adenylate cyclase-activating G-protein coupled receptor signaling pathway • cognition • regulation of insulin secretion • cellular response to glucagon stimulus • intracellular transport • positive regulation of cAMP-mediated signaling • activation of adenylate cyclase activity • cellular response to prostaglandin E stimulus • adenylate cyclase-activating adrenergic receptor signaling pathway • sensory perception of smell • positive regulation of GTPase activity • developmental growth • renal water homeostasis • bone development • platelet aggregation • signal transduction • regulation of signal transduction • skeletal system development • genetic imprinting • multicellular organism growth • positive regulation of osteoclast differentiation • endochondral ossification • regulation of parathyroid hormone secretion • post-embryonic development • post-embryonic body morphogenesis • DNA methylation • cartilage development • positive regulation of osteoblast differentiation • tissue homeostasis • sensory perception of chemical stimulus • embryonic cranial skeleton morphogenesis • energy reserve metabolic process • response to drug • skin development • embryonic hindlimb morphogenesis Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2778	14683
Ensembl	ENSG00000087460	ENSMUSG00000027523
UniProt	O95467 P63092 P84996 Q5JWF2	P63094 Q6R0H7 Q9Z0F1 Q6R0H6
RefSeq (mRNA)	NM_000516 NM_001077488 NM_001077489 NM_001077490 NM_001309840 NM_001309842 NM_001309861 NM_001309883 NM_016592 NM_080425 NM_080426	NM_001077507 NM_001077510 NM_010309 NM_010310 NM_019690 NM_022000 NM_201616 NM_201617 NM_201618 NM_001310083 NM_001310085
RefSeq (protein)	NP_000507.1 NP_001070956.1 NP_001070957.1 NP_001296790.1 NP_057676.1 NP_536351.1 NP_000507.1 NP_001070956.1 NP_001070957.1 NP_001070958.1 NP_001296769.1 NP_536350.2 NP_536351.1 NP_001070958.1 NP_001296812.1 NP_001296812.1 NP_536350.2	NP_001070978.1 NP_001297012.1 NP_963910.1 NP_001070975.1 NP_001297014.1 NP_034439.2 NP_963911.1 NP_062664.2 NP_068840.2 NP_001070975.1 NP_001297014.1 NP_963911.1 NP_963912.1
Location (UCSC)	Chr 20: 58.84 – 58.91 Mb	Chr 2: 174.28 – 174.35 Mb
PubMed search	[1]	[2]
Wikidata

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GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit (G_s-α), a key component of many signal transduction pathways.

Gene

This gene 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 contains 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 exists, and this antisense transcript and one of the transcripts are paternally expressed, produce noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping open reading frame, which encodes a structurally unrelated protein, called ALEX.^[3][4]

The GNAS locus is imprinted and encodes 5 main transcripts:

• G_s-α
• XLAS
• NESP55
• A/B transcript
• antisense GNAS transcript

Protein

Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (G_s-α), a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular responses. Multiple transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined.

Clinical significance

Mutations are associated with:

• Albright hereditary osteodystrophy
• pseudohypoparathyroidism type Ia
• pseudohypoparathyroidism type Ib
• pseudopseudohypoparathyroidism
• McCune-Albright syndrome

Mutations in this gene also result in progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors.^[5]

Interactions

GNAS complex locus has been shown to interact with RIC8A.^[6]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Klemke M, Kehlenbach RH, Huttner WB (July 2001). "Two overlapping reading frames in a single exon encode interacting proteins--a novel way of gene usage". The EMBO Journal. 20 (14): 3849–60. doi:10.1093/emboj/20.14.3849. PMC 125537. PMID 11447126.
4. Abramowitz J, Grenet D, Birnbaumer M, Torres HN, Birnbaumer L (June 2004). "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". Proceedings of the National Academy of Sciences of the United States of America. 101 (22): 8366–71. doi:10.1073/pnas.0308758101. PMC 420400. PMID 15148396.
5. "Entrez Gene: GNAS GNAS complex locus".
6. Klattenhoff C, Montecino M, Soto X, Guzmán L, Romo X, García MA, Mellstrom B, Naranjo JR, Hinrichs MV, Olate J (May 2003). "Human brain synembryn interacts with Gsalpha and Gqalpha and is translocated to the plasma membrane in response to isoproterenol and carbachol". Journal of Cellular Physiology. 195 (2): 151–7. doi:10.1002/jcp.10300. PMID 12652642.

Further reading

• Tinschert S, Gerl H, Gewies A, Jung HP, Nürnberg P (March 1999). "McCune-Albright syndrome: clinical and molecular evidence of mosaicism in an unusual giant patient". American Journal of Medical Genetics. 83 (2): 100–8. doi:10.1002/(SICI)1096-8628(19990312)83:2<100::AID-AJMG5>3.0.CO;2-K. PMID 10190480.
• Faivre L, Nivelon-Chevallier A, Kottler ML, Robinet C, Khau Van Kien P, Lorcerie B, Munnich A, Maroteaux P, Cormier-Daire V, LeMerrer M (March 2001). "Mazabraud syndrome in two patients: clinical overlap with McCune-Albright syndrome". American Journal of Medical Genetics. 99 (2): 132–6. doi:10.1002/1096-8628(2000)9999:999<00::AID-AJMG1135>3.0.CO;2-A. PMID 11241472.
• Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacology & Therapeutics. 92 (2-3): 179–212. doi:10.1016/S0163-7258(01)00169-3. PMID 11916537.
• Weinstein LS, Chen M, Liu J (June 2002). "Gs(alpha) mutations and imprinting defects in human disease". Annals of the New York Academy of Sciences. 968: 173–97. doi:10.1111/j.1749-6632.2002.tb04335.x. PMID 12119276.
• Bastepe M, Jüppner H (2005). "GNAS locus and pseudohypoparathyroidism". Hormone Research. 63 (2): 65–74. doi:10.1159/000083895. PMID 15711092.
• de Sanctis L, Delmastro L, Russo MC, Matarazzo P, Lala R, de Sanctis C (May 2006). "Genetics of McCune-Albright syndrome". Journal of Pediatric Endocrinology & Metabolism. 19 Suppl 2: 577–82. PMID 16789620.
• Aldred MA (May 2006). "Genetics of pseudohypoparathyroidism types Ia and Ic". Journal of Pediatric Endocrinology & Metabolism. 19 Suppl 2: 635–40. PMID 16789628.
• Jüppner H, Bastepe M (May 2006). "Different mutations within or upstream of the GNAS locus cause distinct forms of pseudohypoparathyroidism". Journal of Pediatric Endocrinology & Metabolism. 19 Suppl 2: 641–6. PMID 16789629.
• Mantovani G, Spada A (December 2006). "Mutations in the Gs alpha gene causing hormone resistance". Best Practice & Research. Clinical Endocrinology & Metabolism. 20 (4): 501–13. doi:10.1016/j.beem.2006.09.001. PMID 17161328.

External links

• GNAS protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)