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GNAS GNAS complex locus [ Homo sapiens (human) ]

Gene ID: 2778, updated on 1-Jun-2020

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

Genomic context

See GNAS in Genome Data Viewer
Location:
20q13.32
Exon count:
23
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 20 NC_000020.11 (58839681..58911196)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (57414756..57486250)

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
Cushing's syndrome
MedGen: C1857451 OMIM: 219080 GeneReviews: Not available
Compare labs
McCune-Albright syndrome Compare labs
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
MedGen: C3494506 OMIM: 103580 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
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 (2012-07-12)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-07-12)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
NHGRI GWA Catalog
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
NHGRI GWA Catalog
Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.
NHGRI GWA Catalog
Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide.
NHGRI GWA Catalog
Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.
NHGRI GWA Catalog

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
D1 dopamine receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
G protein-coupled receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
G-protein beta/gamma-subunit complex binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
GTP binding IEA
Inferred from Electronic Annotation
more info
 
GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
adenylate cyclase activator activity ISS
Inferred from Sequence or Structural Similarity
more info
 
beta-2 adrenergic receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
corticotropin-releasing hormone receptor 1 binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
insulin-like growth factor receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ionotropic glutamate receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
mu-type opioid receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
DNA methylation IEA
Inferred from Electronic Annotation
more info
 
adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
adenylate cyclase-activating dopamine receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
adenylate cyclase-modulating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
bone development IMP
Inferred from Mutant Phenotype
more info
PubMed 
cartilage development IEA
Inferred from Electronic Annotation
more info
 
developmental growth IMP
Inferred from Mutant Phenotype
more info
PubMed 
embryonic cranial skeleton morphogenesis IEA
Inferred from Electronic Annotation
more info
 
embryonic hindlimb morphogenesis IEA
Inferred from Electronic Annotation
more info
 
endochondral ossification IEA
Inferred from Electronic Annotation
more info
 
energy reserve metabolic process IEA
Inferred from Electronic Annotation
more info
 
genetic imprinting IEA
Inferred from Electronic Annotation
more info
 
multicellular organism growth IEA
Inferred from Electronic Annotation
more info
 
platelet aggregation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of catalytic activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of osteoblast differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of osteoclast differentiation IEA
Inferred from Electronic Annotation
more info
 
post-embryonic body morphogenesis IEA
Inferred from Electronic Annotation
more info
 
regulation of parathyroid hormone secretion IEA
Inferred from Electronic Annotation
more info
 
sensory perception of chemical stimulus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
skin development IEA
Inferred from Electronic Annotation
more info
 
tissue homeostasis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
apical plasma membrane IEA
Inferred from Electronic Annotation
more info
 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol ISS
Inferred from Sequence or Structural Similarity
more info
 
dendrite IEA
Inferred from Electronic Annotation
more info
 
extracellular exosome HDA PubMed 
heterotrimeric G-protein complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
membrane HDA PubMed 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
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
guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
neuroendocrine secretory protein
secretogranin VI

NCBI Reference Sequences (RefSeq)

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_000516.6NP_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, BU857975
    Consensus CDS
    CCDS13472.1
    UniProtKB/Swiss-Prot
    O95467, P63092
    UniProtKB/TrEMBL
    A0A0S2Z3H8
    Related
    ENSP00000360126.3, ENST00000371085.7
    Conserved Domains (1) summary
    cd00066
    Location:41388
    G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
  2. NM_001077488.4NP_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, BC089157, M14631
    Consensus CDS
    CCDS46623.1
    UniProtKB/Swiss-Prot
    O95467, P63092
    UniProtKB/TrEMBL
    Q5FWY2
    Related
    ENSP00000346328.7, ENST00000354359.11
    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_001077490.2NP_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, BQ230306, X04408
    UniProtKB/Swiss-Prot
    P63092, P84996
    Related
    ENSP00000499607.1, ENST00000464624.6
    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
    cl26635
    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
    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
    ENSP00000302237.3, ENST00000306120.3
    Conserved Domains (1) summary
    PHA03247
    Location:125345
    PHA03247; large tegument protein UL36; Provisional
  9. NM_016592.4NP_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, 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_080425.3NP_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, BQ230306, CN295544, X04408
    Consensus CDS
    CCDS46622.1
    UniProtKB/Swiss-Prot
    P63092, Q5JWF2
    Related
    ENSP00000360141.3, ENST00000371100.8
    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.

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..58911196
    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
    ENSP00000499293.1, ENST00000667293.1
    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

  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

  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

    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
    ENSP00000499332.1, ENST00000488546.5
    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

    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
    ENSP00000499380.1, ENST00000657090.1
    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

    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

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

RNA

  1. XR_002958471.1 RNA Sequence

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