Format

Send to:

Choose Destination
    • Showing Current items.

    GNAS GNAS complex locus [ Homo sapiens (human) ]

    Gene ID: 2778, updated on 8-Jul-2021

    Summary

    Official Symbol
    GNASprovided by HGNC
    Official Full Name
    GNAS complex locusprovided by HGNC
    Primary source
    HGNC:HGNC:4392
    See related
    Ensembl:ENSG00000087460 MIM:139320
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AHO; GSA; GSP; POH; GPSA; NESP; SCG6; SgVI; GNAS1; PITA3; C20orf45
    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. [provided by RefSeq, Aug 2012]
    Expression
    Ubiquitous expression in thyroid (RPKM 405.2), brain (RPKM 137.2) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GNAS in Genome Data Viewer
    Location:
    20q13.32
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 20 NC_000020.11 (58839681..58911192)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (57414803..57486247)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene GNAS antisense RNA 1 Neighboring gene microRNA 296 Neighboring gene microRNA 298 Neighboring gene uncharacterized LOC101927932 Neighboring gene uncharacterized LOC107985382 Neighboring gene small integral membrane protein 30-like Neighboring gene negative elongation factor complex member C/D

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    ACTH-independent macronodular adrenal hyperplasia 1
    MedGen: C1857451 OMIM: 219080 GeneReviews: Not available
    Compare labs
    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
    GeneReviews: Not available
    Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
    GeneReviews: Not available
    Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.
    GeneReviews: Not available
    Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide.
    GeneReviews: Not available
    McCune-Albright syndrome Compare labs
    Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.
    GeneReviews: Not available
    Pituitary adenoma 3, multiple types
    MedGen: C4540135 OMIM: 617686 GeneReviews: Not available
    Compare labs
    Progressive osseous heteroplasia
    MedGen: C0334041 OMIM: 166350 GeneReviews: Disorders of GNAS Inactivation
    Compare labs
    Pseudohypoparathyroidism type 1B
    MedGen: C1864100 OMIM: 603233 GeneReviews: Disorders of GNAS Inactivation
    Compare labs
    Pseudohypoparathyroidism type 1C
    MedGen: C2932716 OMIM: 612462 GeneReviews: Disorders of GNAS Inactivation
    Compare labs
    Pseudohypoparathyroidism type I A
    MedGen: C3494506 OMIM: 103580 GeneReviews: Disorders of GNAS Inactivation
    Compare labs
    Pseudopseudohypoparathyroidism
    MedGen: C0033835 OMIM: 612463 GeneReviews: Disorders of GNAS Inactivation
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2021-01-12)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2021-01-12)

    ClinGen Genome Curation PagePubMed

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC33735

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables D1 dopamine receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables G protein-coupled receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables G-protein beta/gamma-subunit complex binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables GTP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables GTPase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables adenylate cyclase activator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables beta-2 adrenergic receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables corticotropin-releasing hormone receptor 1 binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables insulin-like growth factor receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables ionotropic glutamate receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables mu-type opioid receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in extracellular exosome HDA PubMed 
    part_of heterotrimeric G-protein complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     

    General protein information

    Preferred Names
    protein ALEX; protein GNAS; protein SCG6 (secretogranin VI)
    Names
    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

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016194.2 RefSeqGene

      Range
      56682..76450
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000516.7NP_000507.1  protein GNAS isoform GNASL

      See identical proteins and their annotated locations for NP_000507.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) is biallelically expressed and encodes guanine nucleotide binding protein alpha s long (GNASL), also known as alpha-S2, a form of the G-protein alpha subunit.
      Source sequence(s)
      AF105253, AF493897, BC008855, BU857975
      Consensus CDS
      CCDS13472.1
      UniProtKB/Swiss-Prot
      O95467, P63092
      UniProtKB/TrEMBL
      A0A0S2Z3H8
      Related
      ENSP00000360126.3, ENST00000371085.8
      Conserved Domains (1) summary
      cd00066
      Location:41388
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    2. NM_001077488.5NP_001070956.1  protein GNAS isoform f

      See identical proteins and their annotated locations for NP_001070956.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) is biallelically expressed and uses an alternate in frame splice site, compared to variant 1. It encodes isoform f which has an additional amino acid in the internal region compared to isoform GNASL.
      Source sequence(s)
      AF105253, AF493897, BC008855, BC089157, M14631
      Consensus CDS
      CCDS46623.1
      UniProtKB/Swiss-Prot
      O95467, P63092
      UniProtKB/TrEMBL
      Q5FWY2
      Related
      ENSP00000346328.7, ENST00000354359.12
      Conserved Domains (1) summary
      cd00066
      Location:41389
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    3. NM_001077489.4NP_001070957.1  protein GNAS isoform g

      See identical proteins and their annotated locations for NP_001070957.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) is biallelically expressed and lacks an alternate in-frame coding exon, compared to variant 1. It encodes isoform g, which lacks an internal segment, compared to isoform GNASL.
      Source sequence(s)
      AF105253, AF493897, BC066923, BC089157
      Consensus CDS
      CCDS42892.1
      UniProtKB/Swiss-Prot
      O95467, P63092
      UniProtKB/TrEMBL
      Q5FWY2
      Related
      ENSP00000265620.7, ENST00000265620.11
      Conserved Domains (1) summary
      cd00066
      Location:41373
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    4. NM_001077490.3NP_001070958.1  protein ALEX isoform Alex

      See identical proteins and their annotated locations for NP_001070958.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as GNASXL), is paternally expressed and includes an alternate 5' exon, compared to variant 1. This variant includes two overlapping ORFs encoding XLas and Alex, respectively. This RefSeq represents Alex (also known as alexX), which has no similarity to other proteins encoded by this gene. It interacts with XLas, and their interaction is essential for G-protein signaling in neuroendocrine cells.
      Source sequence(s)
      AL132655, BQ029639, X04408
      UniProtKB/Swiss-Prot
      P63092, P84996
      Conserved Domains (1) summary
      PHA03247
      Location:125345
      PHA03247; large tegument protein UL36; Provisional
    5. NM_001309840.2NP_001296769.1  protein ALEX isoform h

      See identical proteins and their annotated locations for NP_001296769.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) is paternally expressed, contains an alternate 5' terminal exon (A/B or Exon 1A) and uses a downstream start codon, compared to variant 1. Variants 9 and 11 encode the same isoform h (described in PMID:21713996), which has a shorter N-terminus, compared to isoform GNASL.
      Source sequence(s)
      AL537118, CN403086, X04408, X56009
      UniProtKB/Swiss-Prot
      P63092
      UniProtKB/TrEMBL
      B0AZR9, Q14455
      Related
      ENSP00000499660.1, ENST00000477931.5
      Conserved Domains (1) summary
      cd00066
      Location:1329
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    6. NM_001309842.2NP_001296771.1  protein ALEX isoform i

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) contains an alternate 3' exon structure, compared to variant 1. It encodes isoform i, which has a shorter and distinct C-terminus, compared to isoform GNASL.
      Source sequence(s)
      AA948160, BC089157, BF800576, BF879848, CB530031, DB483472
      Consensus CDS
      CCDS82633.1
      UniProtKB/TrEMBL
      Q5FWY2, Q5JWD1
      Related
      ENSP00000360122.1, ENST00000371081.5
      Conserved Domains (1) summary
      smart00275
      Location:2071
      G_alpha; G protein alpha subunit
    7. NM_001309861.2NP_001296790.1  protein ALEX isoform h

      See identical proteins and their annotated locations for NP_001296790.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (11) contains an alternate 5' terminal exon, compared to variant 1. Variants 9 and 11 encode the same isoform h (described in PMID:21713996), which has a shorter N-terminus, compared to isoform GNASL.
      Source sequence(s)
      AF105253, AK315874, CN273438
      UniProtKB/Swiss-Prot
      O95467
      UniProtKB/TrEMBL
      B0AZR9
      Related
      ENSP00000499673.2, ENST00000472183.6
      Conserved Domains (1) summary
      cd00066
      Location:1329
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    8. NM_001309883.1NP_001296812.1  protein ALEX isoform Alex

      See identical proteins and their annotated locations for NP_001296812.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (12) contains an alternate 5' exon structure compared to variant 1. It encodes the protein Alex (also known as alexX), which has no similarity to other proteins encoded by this gene. It interacts with XLas, and their interaction is essential for G-protein signaling in neuroendocrine cells. Variants 2 and 12 encode the same protein (Alex).
      Source sequence(s)
      AA948160, AJ224867, AL132655, BF800576, BF879848
      UniProtKB/Swiss-Prot
      P84996, Q5JWF2
      Related
      ENSP00000302237.4, ENST00000306120.4
      Conserved Domains (1) summary
      PHA03247
      Location:125345
      PHA03247; large tegument protein UL36; Provisional
    9. NM_016592.5NP_057676.1  protein SCG6 (secretogranin VI) isoform SCG6

      See identical proteins and their annotated locations for NP_057676.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) is maternally expressed and encodes secretogranin VI (SCG6, also known as NESP55), which localizes to large secretory vesicles of endocrine cells and neurons. Its coding region is within the 5'-most exon and does not overlap the coding regions used by other transcripts; thus SCG6 has no similarity to isoforms of the G-protein alpha subunit. This variant has an antisense transcript, GNAS-AS1.
      Source sequence(s)
      AF105253, AL132655, BC008855, BC036081
      Consensus CDS
      CCDS13471.1
      UniProtKB/Swiss-Prot
      O95467
      Related
      ENSP00000360115.3, ENST00000371075.7
      Conserved Domains (1) summary
      pfam06390
      Location:1245
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
    10. NM_080425.4NP_536350.2  protein GNAS isoform XLas

      See identical proteins and their annotated locations for NP_536350.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as GNASXL) is paternally expressed and includes an alternate 5' exon, compared to variant 1. This variant includes two overlapping open reading frames encoding isoforms XLas and Alex, respectively. This RefSeq represents isoform XLas (also known as alpha sXXL), which is a neuroendocrine-specific G-protein alpha subunit. The encoded isoform has a distinct and longer N-terminus, compared to isoform GNASL. Variants 2 and 12 both encode the same isoform (Alex).
      Source sequence(s)
      AL132655, BQ029639, CN295544, X04408
      Consensus CDS
      CCDS46622.1
      UniProtKB/Swiss-Prot
      P63092, Q5JWF2
      Related
      ENSP00000360141.3, ENST00000371100.9
      Conserved Domains (2) summary
      cd00066
      Location:6841031
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
      smart00275
      Location:6631034
      G_alpha; G protein alpha subunit
    11. NM_080426.4NP_536351.1  protein GNAS isoform GNASS

      See identical proteins and their annotated locations for NP_536351.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is biallelically expressed. It lacks an internal exon and uses an alternate splice site, compared to variant 1. It encodes isoform GNASS, also known as alpha-S1, which differs in an internal region and has identical N- and C-termini, compared to isoform GNASL.
      Source sequence(s)
      AF105253, AF493897, BC089157
      Consensus CDS
      CCDS46624.1
      UniProtKB/Swiss-Prot
      O95467, P63092
      UniProtKB/TrEMBL
      A0A0S2Z3S5, Q5FWY2
      Related
      ENSP00000360136.3, ENST00000371095.7
      Conserved Domains (1) summary
      cd00066
      Location:41374
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)

    RNA

    1. NR_132272.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (13) contains alternate 5' and 3' terminal exons, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AA948160, AL121917, BF800576, BF879848, HY141824
    2. NR_132273.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (14) contains alternate 5' and 3' terminal exons, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AA948160, AL121917, AV751821, BF800576, BF879848, BM894355
      Related
      ENST00000464960.5

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p13 Primary Assembly

      Range
      58839681..58911192
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017027821.1XP_016883310.1  protein SCG6 (secretogranin VI) isoform X9

      UniProtKB/Swiss-Prot
      O95467
      Conserved Domains (1) summary
      pfam06390
      Location:1245
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
    2. XM_017027822.1XP_016883311.1  protein SCG6 (secretogranin VI) isoform X9

      UniProtKB/Swiss-Prot
      O95467
      Related
      ENSP00000360139.2, ENST00000371098.6
      Conserved Domains (1) summary
      pfam06390
      Location:1245
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
    3. XM_024451872.1XP_024307640.1  protein GNAS isoform X4

      Related
      ENSP00000304472.12, ENST00000306090.12
      Conserved Domains (1) summary
      cd00066
      Location:5356
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    4. XM_017027815.1XP_016883304.1  protein GNAS isoform X5

      Conserved Domains (1) summary
      cd00066
      Location:5341
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    5. XM_017027812.2XP_016883301.1  protein GNAS isoform X1

      Related
      ENSP00000504675.2, ENST00000676826.2
    6. XM_017027813.2XP_016883302.1  protein GNAS isoform X2

      UniProtKB/Swiss-Prot
      Q5JWF2
      Related
      ENSP00000360143.4, ENST00000371102.8
    7. XM_017027814.2XP_016883303.1  protein GNAS isoform X3

      Related
      ENSP00000265621.6, ENST00000349036.9
    8. XM_017027817.1XP_016883306.1  protein ALEX isoform X8

      Related
      ENSP00000499392.1, ENST00000480975.5
      Conserved Domains (1) summary
      cd00066
      Location:1314
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    9. XM_024451875.1XP_024307643.1  protein ALEX isoform X6

      Related
      ENSP00000474219.2, ENST00000604005.6
      Conserved Domains (1) summary
      cd00066
      Location:1329
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    10. XM_017027819.1XP_016883308.1  protein ALEX isoform X8

      Related
      ENSP00000499794.2, ENST00000482112.6
      Conserved Domains (1) summary
      cd00066
      Location:1314
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    11. XM_017027816.1XP_016883305.1  protein ALEX isoform X7

      Conserved Domains (1) summary
      cd00066
      Location:11314
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    12. XM_017027818.2XP_016883307.1  protein ALEX isoform X8

      Related
      ENSP00000499409.2, ENST00000476935.6
      Conserved Domains (1) summary
      cd00066
      Location:1314
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    13. XM_024451873.1XP_024307641.1  protein ALEX isoform X6

      Related
      ENSP00000499435.2, ENST00000488652.6
      Conserved Domains (1) summary
      cd00066
      Location:1329
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    14. XM_024451874.1XP_024307642.1  protein ALEX isoform X6

      Related
      ENSP00000474802.2, ENST00000603546.2
      Conserved Domains (1) summary
      cd00066
      Location:1329
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
    15. XM_017027820.1XP_016883309.1  protein ALEX isoform X7

      Related
      ENSP00000507069.1, ENST00000682803.1
      Conserved Domains (1) summary
      cd00066
      Location:11314
      G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)

    RNA

    1. XR_002958471.1 RNA Sequence

    Support Center