An official website of the United States government

GNAS - GNAS complex locus (human)

Gene
Symbol
Dates
  • Create:
    2016-09-14
  • Modify:
    2025-02-01
Description
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. [provided by RefSeq, Aug 2012]
Enables D1 dopamine receptor binding activity; G protein activity; and adenylate cyclase regulator activity. Involved in several processes, including adenylate cyclase-activating G protein-coupled receptor signaling pathway; hair follicle placode formation; and platelet aggregation. Located in several cellular components, including cytosol; perinuclear region of cytoplasm; and trans-Golgi network membrane. Implicated in several diseases, including ACTH-independent macronodular adrenal hyperplasia 1; obesity; pituitary adenoma 3; progressive osseous heteroplasia; and pseudohypoparathyroidism (multiple). Biomarker of Alzheimer's disease; pancreatic cancer; and pseudohypoparathyroidism type IB.

The GNAS gene provides instructions for making one component, the stimulatory alpha subunit, of a protein complex called a guanine nucleotide-binding protein (G protein). Each G protein is composed of three proteins called the alpha, beta, and gamma subunits.

In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions by regulating the activity of hormones. The G protein made with the subunit produced from the GNAS gene helps stimulate the activity of an enzyme called adenylate cyclase. This enzyme is involved in controlling the production of several hormones that help regulate the activity of endocrine glands such as the thyroid, pituitary gland, ovaries and testes (gonads), and adrenal glands. Adenylate cyclase is also believed to play a key role in signaling pathways that help regulate the development of bone (osteogenesis). In this way, the enzyme helps prevent the body from producing bone tissue in the wrong place (ectopic bone).

1 Names and Identifiers

1.1 Synonyms

  • AHO
  • AIMAH1
  • 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
  • secretogranin VI

1.2 Other Identifiers

1.2.1 HGNC ID

1.2.2 Ensembl ID

1.2.3 Alliance Gene ID

1.2.4 Bgee Gene ID

1.2.5 Enzyme Commission (EC) Number

1.2.6 GenCC ID

1.2.7 KEGG Gene

1.2.8 MIM Number

1.2.9 NCI Thesaurus Code

1.2.10 Open Targets ID

1.2.11 PharmGKB ID

1.2.12 Pharos Target

1.2.13 VEuPathDB ID

1.2.14 Wikidata

3 Proteins

3.1 Protein Function

Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PMID: 12391161, PMID: 17110384, PMID: 21488135, PMID: 26206488, PMID: 8702665, PMID: 10200251). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PMID: 12391161, PMID: 17110384, PMID: 10200251). Signaling by an activated GPCR promotes GDP release and GTP binding (PMID: 12391161, PMID: 17110384, PMID: 10200251). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PMID: 12391161, PMID: 17110384, PMID: 10200251). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PMID: 12391161, PMID: 17110384, PMID: 10200251). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PMID: 17110384, PMID: 26206488, PMID: 26206488, PMID: 8702665). Functions downstream of beta-adrenergic receptors (PMID: 21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PMID: 12391161).
May inhibit the adenylyl cyclase-stimulating activity of guanine nucleotide-binding protein G(s) subunit alpha which is produced from the same locus in a different open reading frame.
Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as Gnas isoforms.

3.2 Protein Isoforms

1 of 3
Isoform
Isoform Nesp55
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-1
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-2
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-3
UniProt ID
RefSeq Accession
Isoform
Isoform Gnas-1
UniProt ID
RefSeq Accession
Isoform
Isoform Gnas-2
UniProt ID
RefSeq Accession
Isoform
Isoform 3
UniProt ID
RefSeq Accession
Isoform
Isoform 4
UniProt ID
RefSeq Accession
2 of 3
Isoform
Isoform Gnas-1
UniProt ID
RefSeq Accession
Isoform
Isoform Gnas-2
UniProt ID
RefSeq Accession
Isoform
Isoform 3
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-1
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-2
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-3
UniProt ID
RefSeq Accession
Isoform
Isoform Nesp55
UniProt ID
RefSeq Accession
Isoform
Isoform 4
UniProt ID
RefSeq Accession
3 of 3
Isoform
Isoform XLas-1
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-2
UniProt ID
RefSeq Accession
Isoform
Isoform XLas-3
UniProt ID
RefSeq Accession
Isoform
Isoform Gnas-1
UniProt ID
RefSeq Accession
Isoform
Isoform 3
UniProt ID
RefSeq Accession
Isoform
Isoform Gnas-2
UniProt ID
RefSeq Accession
Isoform
Isoform Nesp55
UniProt ID
RefSeq Accession
Isoform
Isoform 4
UniProt ID
RefSeq Accession

3.3 Protein 3D Structures

3.3.1 PDB Structures

3.3.2 NCBI Protein Structures

3.3.3 AlphaFold Structures

Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605

3.4 Protein Targets

4 Chemicals and Bioactivities

4.1 Tested Compounds

5 BioAssays

5.1 Small-Molecule BioAssays

5.2 RNAi BioAssays

6 Diseases and Phenotypes

6.1 GHR Health Conditions

6.2 KEGG Diseases

6.3 OMIM Phenotypes

6.4 MedGen Diseases

6.5 Gene-Disease Associations

7 Interactions and Pathways

7.1 Chemical-Gene Interactions

7.2 Interactions

7.3 Pathways

8 Biochemical Reactions

9 Cell Lines

10 Expression

11 Target Development Level

12 Literature

12.1 Consolidated References

12.2 Gene-Chemical Co-Occurrences in Literature

12.3 Gene-Gene Co-Occurrences in Literature

12.4 Gene-Disease Co-Occurrences in Literature

13 Patents

13.1 Gene-Chemical Co-Occurrences in Patents

13.2 Gene-Gene Co-Occurrences in Patents

13.3 Gene-Disease Co-Occurrences in Patents

14 Classification

14.1 Gene Family

14.2 NCI Thesaurus Tree

14.3 Gene Ontology: Biological Process

14.4 Gene Ontology: Cellular Component

14.5 Gene Ontology: Molecular Function

14.6 ChEMBL Target Tree

15 Information Sources

  1. NCBI Gene
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  2. PubChem
  3. Alliance of Genome Resources
    LICENSE
    All annotations and data produced by Alliance members that are accessible from alliancegenome.org are distributed under a CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
    https://www.alliancegenome.org/privacy-warranty-licensing
  4. MedlinePlus Genetics
    LICENSE
    Terms and conditions of use apply to all persons or organizations that publish or distribute content from the MedlinePlus website.
    https://medlineplus.gov/about/using/usingcontent/
  5. BioGRID
    LICENSE
    The MIT License (MIT); Copyright Mike Tyers Lab
    https://wiki.thebiogrid.org/doku.php/terms_and_conditions
  6. STRING: functional protein association networks
  7. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  8. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  9. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  10. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  11. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  12. Dependency Map (DepMap)
  13. Gene Curation Coalition (GenCC)
    LICENSE
    The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication.
    https://thegencc.org/terms.html
    GNAS
  14. HUGO Gene Nomenclature Committee (HGNC)
    LICENSE
    No restrictions are imposed on access to, or use of, the data provided by the HGNC, which are provided to enhance knowledge and encourage progress in the scientific community.
    https://www.genenames.org/about/
  15. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  16. NCBI Gene Expression Omnibus (GEO)
  17. NCBI MedGen
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  18. NCBI Structure
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  19. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  20. Online Mendelian Inheritance in Man (OMIM)
    LICENSE
    The OMIM database is made available to the general public subject to certain restrictions.
    https://omim.org/help/copyright
  21. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  22. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  23. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  24. Swiss Institute of Bioinformatics Bgee
    LICENSE
    Creative Commons Zero license (CC0)
    https://www.bgee.org/about/
  25. UniProt
    LICENSE
    We have chosen to apply the Creative Commons Attribution (CC BY 4.0, http://creativecommons.org/licenses/by/4.0/) License to all copyrightable parts of our databases.
    https://www.uniprot.org/help/license
  26. VEuPathDB: The Eukaryotic Pathogen, Vector and Host Informatics Resource
    LICENSE
    All data on VEuPathDB websites are provided freely for public use.
    https://veupathdb.org/veupathdb/app/static-content/about.html
  27. Wikidata
  28. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  29. Gene Ontology (GO)
    LICENSE
    Gene Ontology Consortium data and data products are licensed under the Creative Commons Attribution 4.0 Unported License (https://creativecommons.org/licenses/by/4.0/legalcode)
    http://geneontology.org/docs/go-citation-policy/
  30. AlphaFold DB
    LICENSE
    All of the data provided is freely available for both academic and commercial use under Creative Commons Attribution 4.0 (CC-BY 4.0) licence terms.
    https://alphafold.ebi.ac.uk/faq
  31. Rhea - annotated reactions database
    LICENSE
    Rhea has chosen to apply the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). This means that you are free to copy, distribute, display and make commercial use of the database in all legislations, provided you credit (cite) Rhea.
    https://www.rhea-db.org/help/license-disclaimer
CONTENTS