GNAS

Protein identityUniProt · HPA

UniProt accession

Q5JWF2

Gene

GNAS

Ensembl

ENSG00000087460

Chromosome

20

Canonical length

1037 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Plasma membrane,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1037 residues, UniProt reviewed canonical sequence.

>Q5JWF2|GNAS
     1  MGVRNCLYGN NMSGQRDIPP EIGEQPEQPP LEAPGAAAPG AGPSPAEEME TEPPHNEPIP
    61  VENDGEACGP PEVSRPNFQV LNPAFREAGA HGSYSPPPEE AMPFEAEQPS LGGFWPTLEQ
   121  PGFPSGVHAG LEAFGPALME PGAFSGARPG LGGYSPPPEE AMPFEFDQPA QRGCSQLLLQ
   181  VPDLAPGGPG AAGVPGAPPE EPQALRPAKA GSRGGYSPPP EETMPFELDG EGFGDDSPPP
   241  GLSRVIAQVD GSSQFAAVAA SSAVRLTPAA NAPPLWVPGA IGSPSQEAVR PPSNFTGSSP
   301  WMEISGPPFE IGSAPAGVDD TPVNMDSPPI ALDGPPIKVS GAPDKRERAE RPPVEEEAAE
   361  MEGAADAAEG GKVPSPGYGS PAAGAASADT AARAAPAAPA DPDSGATPED PDSGTAPADP
   421  DSGAFAADPD SGAAPAAPAD PDSGAAPDAP ADPDSGAAPD APADPDAGAA PEAPAAPAAA
   481  ETRAAHVAPA APDAGAPTAP AASATRAAQV RRAASAAPAS GARRKIHLRP PSPEIQAADP
   541  PTPRPTRASA WRGKSESSRG RRVYYDEGVA SSDDDSSGDE SDDGTSGCLR WFQHRRNRRR
   601  RKPQRNLLRN FLVQAFGGCF GRSESPQPKA SRSLKVKKVP LAEKRRQMRK EALEKRAQKR
   661  AEKKRSKLID KQLQDEKMGY MCTHRLLLLG AGESGKSTIV KQMRILHVNG FNGEGGEEDP
   721  QAARSNSDGE KATKVQDIKN NLKEAIETIV AAMSNLVPPV ELANPENQFR VDYILSVMNV
   781  PDFDFPPEFY EHAKALWEDE GVRACYERSN EYQLIDCAQY FLDKIDVIKQ ADYVPSDQDL
   841  LRCRVLTSGI FETKFQVDKV NFHMFDVGGQ RDERRKWIQC FNDVTAIIFV VASSSYNMVI
   901  REDNQTNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR
   961  YTTPEDATPE PGEDPRVTRA KYFIRDEFLR ISTASGDGRH YCYPHFTCAV DTENIRRVFN
  1021  DCRDIIQRMH LRQYELL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GNAS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.56

Highest tissue expression

3,737 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GNAS.

Disease | AllUniProt

Conditions GNAS is implicated in, by any mechanism.

• ACTH-independent macronodular adrenal hyperplasia 1 (AIMAH1) MIM:219080
• Pseudohypoparathyroidism 1B (PHP1B) MIM:603233
• Pseudohypoparathyroidism 1C (PHP1C) MIM:612462

Disease | GeneticClinVar

238 pathogenic / likely-pathogenic of 1,309 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pseudohypoparathyroidism type I A
• GNAS-related disorder
• Pseudopseudohypoparathyroidism
• Pseudohypoparathyroidism
• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on GNAS was assayed in.

• type 1 diabetes mellitus T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.37

gnomAD pLI

0.68

gnomAD missense Z

2.65

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating dopamine receptor signaling pathway
• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• bone development
• developmental growth
• platelet aggregation
• positive regulation of cold-induced thermogenesis
• sensory perception of chemical stimulus

Molecular functions

• adenylate cyclase activator activity
• beta-2 adrenergic receptor binding
• corticotropin-releasing hormone receptor 1 binding
• D1 dopamine receptor binding
• G protein activity
• G-protein beta/gamma-subunit complex binding
• GTP binding
• GTPase activity
• insulin-like growth factor receptor binding
• ionotropic glutamate receptor binding
• metal ion binding
• mu-type opioid receptor binding

Cellular components

• apical plasma membrane
• cytoplasm
• cytosol
• extracellular exosome
• heterotrimeric G-protein complex
• membrane

Protein domainsUniProt · Pfam · InterPro

• G-protein alpha subunit, group S
• Guanine nucleotide binding protein, alpha subunit
• G protein alpha subunit, helical insertion
• P-loop containing nucleoside triphosphate hydrolase
• G-protein alpha subunit

KeywordsUniProt

• ADP-ribosylation
• Cell membrane
• Coiled coil
• Cushing syndrome
• GTP-binding
• Hydrolase
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Transducer

InteractionsUniProt · HPA

Protein binding partners of GNAS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAGED2
• GPR3
• OPRM1
• GPR12
• MC4R
• HRH2
• TSHR
• RIC8B
• ADCY2
• GCGR
• GPR6
• GAS2L2
• ADCY5
• SASH1
• GNB1