GNAS complex locus

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GNAS complex locus
Protein GNAS PDB 1azs.png
PDB rendering based on 1azs.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GNAS ; AHO; C20orf45; GNAS1; GPSA; GSA; GSP; NESP; PHP1A; PHP1B; PHP1C; POH
External IDs OMIM139320 MGI95777 HomoloGene55534 ChEMBL: 4377 GeneCards: GNAS Gene
RNA expression pattern
PBB GE GNAS 200780 x at tn.png
PBB GE GNAS 200981 x at tn.png
PBB GE GNAS 211858 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2778 14683
Ensembl ENSG00000087460 ENSMUSG00000027523
UniProt O95467 Q9Z0F1
RefSeq (mRNA) NM_000516 NM_010310
RefSeq (protein) NP_000507 NP_034440
Location (UCSC) Chr 20:
57.41 – 57.49 Mb
Chr 2:
173.93 – 173.99 Mb
PubMed search [1] [2]

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 (Gs), a key component of many signal transduction pathways.

Gene[edit]

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 ORF, which encodes a structurally unrelated protein.

The GNAS locus is imprinted and encodes 5 main transcripts:

  • Gs
  • XLAS
  • NESP55
  • A/B transcript
  • antisense GNAS transcript

Protein[edit]

Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (Gs), 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[edit]

Deficiencies are associated with:

Mutations in this gene also result in progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors.[1]

Interactions[edit]

GNAS complex locus has been shown to interact with RIC8A.[2]

References[edit]

  1. ^ "Entrez Gene: GNAS GNAS complex locus". 
  2. ^ Klattenhoff, Carla; Montecino Martín; Soto Ximena; Guzmán Leonardo; Romo Ximena; García María Angeles; Mellstrom Britt; Naranjo José Ramón; Hinrichs María Victoria; Olate Juan (May 2003). "Human brain synembryn interacts with Gsalpha and Gqalpha and is translocated to the plasma membrane in response to isoproterenol and carbachol". J. Cell. Physiol. (United States) 195 (2): 151–7. doi:10.1002/jcp.10300. ISSN 0021-9541. PMID 12652642. 

Further reading[edit]

  • Tinschert S, Gerl H, Gewies A, et al. (1999). "McCune-Albright syndrome: clinical and molecular evidence of mosaicism in an unusual giant patient.". Am. J. Med. Genet. 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, et al. (2001). "Mazabraud syndrome in two patients: clinical overlap with McCune-Albright syndrome.". Am. J. Med. Genet. 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, et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction.". Pharmacol. Ther. 92 (2-3): 179–212. doi:10.1016/S0163-7258(01)00169-3. PMID 11916537. 
  • Weinstein LS, Chen M, Liu J (2002). "Gs(alpha) mutations and imprinting defects in human disease.". Ann. N. Y. Acad. Sci. 968: 173–97. doi:10.1111/j.1749-6632.2002.tb04335.x. PMID 12119276. 
  • Bastepe M, Jüppner H (2005). "GNAS locus and pseudohypoparathyroidism.". Horm. Res. 63 (2): 65–74. doi:10.1159/000083895. PMID 15711092. 
  • de Sanctis L, Delmastro L, Russo MC, et al. (2006). "Genetics of McCune-Albright syndrome.". J. Pediatr. Endocrinol. Metab. 19 Suppl 2: 577–82. PMID 16789620. 
  • Aldred MA (2006). "Genetics of pseudohypoparathyroidism types Ia and Ic.". J. Pediatr. Endocrinol. Metab. 19 Suppl 2: 635–40. PMID 16789628. 
  • Jüppner H, Bastepe M (2006). "Different mutations within or upstream of the GNAS locus cause distinct forms of pseudohypoparathyroidism.". J. Pediatr. Endocrinol. Metab. 19 Suppl 2: 641–6. PMID 16789629. 
  • Mantovani G, Spada A (2007). "Mutations in the Gs alpha gene causing hormone resistance.". Best Pract. Res. Clin. Endocrinol. Metab. 20 (4): 501–13. doi:10.1016/j.beem.2006.09.001. PMID 17161328. 

External links[edit]