Human Gene GNAS (ENST00000371100.9) from GENCODE V44
Description: Homo sapiens GNAS complex locus (GNAS), transcript variant 2, mRNA. (from RefSeq NM_080425) RefSeq Summary (NM_001077490): 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]. Gencode Transcript: ENST00000371100.9 Gencode Gene: ENSG00000087460.29 Transcript (Including UTRs) Position: hg38 chr20:58,852,716-58,911,192 Size: 58,477 Total Exon Count: 13 Strand: + Coding Region Position: hg38 chr20:58,853,266-58,910,829 Size: 57,564 Coding Exon Count: 13
ID:GNAS1_HUMAN DESCRIPTION: RecName: Full=Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas; AltName: Full=Adenylate cyclase-stimulating G alpha protein; AltName: Full=Extra large alphas protein; Short=XLalphas; FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. XLas isoforms interact with the same set of receptors as Gnas isoforms (By similarity). SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts through its N-terminal region with ALEX which is produced from the same locus in a different open reading frame. This interaction may inhibit its adenylyl cyclase-stimulating activity (By similarity). SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein (By similarity). DISEASE: Defects in GNAS are the cause of GNAS hyperfunction (GNASHYP) [MIM:139320]. This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms. DISEASE: Defects in GNAS are a cause of ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]; also known as adrenal Cushing syndrome due to AIMAH. A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. DISEASE: Genetic variations in GNAS are the cause of pseudohypoparathyroidism type 1B (PHP1B) [MIM:603233]. PHP1B is characterized by parathyroid hormone (PTH)-resistant hypocalcemia and hyperphosphatemia. Patients affected with PHP1B have normal activity of the product of GNAS, lack developmental defects characteristic of AHO, and typically show no other endocrine abnormalities besides resistance to PTH. Note=Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed. DISEASE: Defects in GNAS are the cause of pseudohypoparathyroidism type 1C (PHP1C) [MIM:612462]. It is a disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification. MISCELLANEOUS: This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame (By similarity). MISCELLANEOUS: The GNAS locus is imprinted in a complex manner, giving rise to distinct paternally, maternally and biallelically expressed proteins. The XLas isoforms are paternally derived, the Gnas isoforms are biallelically derived and the Nesp55 isoforms are maternally derived. SIMILARITY: Belongs to the G-alpha family. G(s) subfamily. SEQUENCE CAUTION: Sequence=CAB83215.1; Type=Frameshift; Positions=40; Sequence=CAM28315.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q5JWF2
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LF205101 - JP 2014500723-A/12604: Polycomb-Associated Non-Coding RNAs. MA440678 - JP 2018138019-A/12604: Polycomb-Associated Non-Coding RNAs. LF205103 - JP 2014500723-A/12606: Polycomb-Associated Non-Coding RNAs. MA440680 - JP 2018138019-A/12606: Polycomb-Associated Non-Coding RNAs. LF206050 - JP 2014500723-A/13553: Polycomb-Associated Non-Coding RNAs. MA441627 - JP 2018138019-A/13553: Polycomb-Associated Non-Coding RNAs. BC036081 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:5302402), containing frame-shift errors. AF105253 - Homo sapiens neuroendocrine secretory protein 55 mRNA, complete cds. AK315874 - Homo sapiens cDNA, FLJ79523 complete cds, highly similar to Guanine nucleotide-binding protein G(s)subunit alpha. LF211876 - JP 2014500723-A/19379: Polycomb-Associated Non-Coding RNAs. MA447453 - JP 2018138019-A/19379: Polycomb-Associated Non-Coding RNAs. LF350848 - JP 2014500723-A/158351: Polycomb-Associated Non-Coding RNAs. MA586425 - JP 2018138019-A/158351: Polycomb-Associated Non-Coding RNAs. AJ224867 - Homo sapiens mRNA for GNAS1 protein (IMAGE cDNA clone 359933 (827-k06)). X56009 - Human GSA mRNA for alpha subunit of GsGTP binding protein. AK026564 - Homo sapiens cDNA: FLJ22911 fis, clone KAT05860, highly similar to HSGSA2R Human mRNA for coupling protein G(s) alpha subunit (alpha-S2) (stimulatory regulatory component Gs of adenylyl cyclase). AK225818 - Homo sapiens mRNA for guanine nucleotide binding protein, alpha stimulating activity polypeptide 1 isoform b variant, clone: FCC129A01. BC089157 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:6647888), complete cds. BC008855 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:4106768), complete cds. BC108315 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:6092583), complete cds. BC002722 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:3627815), complete cds. BC104928 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:8143931), complete cds. X04408 - Human mRNA for coupling protein G(s) alpha subunit (alpha-S2) (stimulatory regulatory component Gs of adenylyl cyclase). X04409 - Human mRNA for coupling protein G(s) alpha-subunit (alpha-S1) (stimulatory regulatory component Gs of adenylyl cyclase). X07036 - Human mRNA stimulatory GTP-binding protein alpha subunit. AB385065 - Synthetic construct DNA, clone: pF1KB5212, Homo sapiens GNAS gene for guanine nucleotide-binding protein G, complete cds, without stop codon, in Flexi system. EU832170 - Synthetic construct Homo sapiens clone HAIB:100067199; DKFZo008H0125 GNAS complex locus protein (GNAS) gene, encodes complete protein. EU832264 - Synthetic construct Homo sapiens clone HAIB:100067293; DKFZo004H0126 GNAS complex locus protein (GNAS) gene, encodes complete protein. CU678144 - Synthetic construct Homo sapiens gateway clone IMAGE:100017171 5' read GNAS mRNA. CU679149 - Synthetic construct Homo sapiens gateway clone IMAGE:100017175 5' read GNAS mRNA. KJ905761 - Synthetic construct Homo sapiens clone ccsbBroadEn_15431 GNAS gene, encodes complete protein. HQ448266 - Synthetic construct Homo sapiens clone IMAGE:100071668; CCSB008993_02 GNAS complex locus (GNAS) gene, encodes complete protein. KJ891258 - Synthetic construct Homo sapiens clone ccsbBroadEn_00652 GNAS gene, encodes complete protein. KR710750 - Synthetic construct Homo sapiens clone CCSBHm_00016693 GNAS (GNAS) mRNA, encodes complete protein. KR710751 - Synthetic construct Homo sapiens clone CCSBHm_00016697 GNAS (GNAS) mRNA, encodes complete protein. KR710752 - Synthetic construct Homo sapiens clone CCSBHm_00016711 GNAS (GNAS) mRNA, encodes complete protein. KR710753 - Synthetic construct Homo sapiens clone CCSBHm_00016735 GNAS (GNAS) mRNA, encodes complete protein. KU178095 - Homo sapiens GNAS complex locus isoform 1 (GNAS) mRNA, partial cds. KU178096 - Homo sapiens GNAS complex locus isoform 2 (GNAS) mRNA, partial cds, alternatively spliced. BT009905 - Homo sapiens GNAS complex locus mRNA, complete cds. AF064092 - Homo sapiens mutant guanine nucleotide-binding protein G(s), alpha subunit mRNA, complete cds. AF088184 - Homo sapiens guanine nucleotide-binding protein Gs alpha subunit isoform L2 mRNA, complete cds. AF493897 - Homo sapiens guanine nucleotide binding protein alpha s long (GNASL) mRNA, complete cds. AF493898 - Homo sapiens guanine nucleotide binding protein alpha s short (GNASS) mRNA, complete cds. BC066923 - Homo sapiens GNAS complex locus, mRNA (cDNA clone IMAGE:4814812), complete cds. M14631 - Human guanine nucleotide-binding protein G-s, alpha subunit mRNA, partial cds. AK315860 - Homo sapiens cDNA, FLJ79509 complete cds, highly similar to Guanine nucleotide-binding protein G(s)subunit alpha. BC022875 - Homo sapiens, Similar to GNAS complex locus, clone IMAGE:4108909, mRNA, partial cds. AK093534 - Homo sapiens cDNA FLJ36215 fis, clone THYMU2000684, highly similar to Guanine nucleotide-binding protein G-s-alpha-4. M77026 - Homo sapiens adenyl cyclase mRNA. LF350865 - JP 2014500723-A/158368: Polycomb-Associated Non-Coding RNAs. MA586442 - JP 2018138019-A/158368: Polycomb-Associated Non-Coding RNAs. AK054862 - Homo sapiens cDNA FLJ30300 fis, clone BRACE2003210, highly similar to GUANINE NUCLEOTIDE-BINDING PROTEIN G(S), ALPHA SUBUNIT. JD407185 - Sequence 388209 from Patent EP1572962. AK122771 - Homo sapiens cDNA FLJ16311 fis, clone SPLEN2010187, highly similar to GUANINE NUCLEOTIDE-BINDING PROTEIN G(S), ALPHA SUBUNIT. JD053470 - Sequence 34494 from Patent EP1572962. JD470183 - Sequence 451207 from Patent EP1572962. LF350873 - JP 2014500723-A/158376: Polycomb-Associated Non-Coding RNAs. MA586450 - JP 2018138019-A/158376: Polycomb-Associated Non-Coding RNAs. JD222493 - Sequence 203517 from Patent EP1572962. JD564227 - Sequence 545251 from Patent EP1572962. JD346797 - Sequence 327821 from Patent EP1572962. LF350875 - JP 2014500723-A/158378: Polycomb-Associated Non-Coding RNAs. MA586452 - JP 2018138019-A/158378: Polycomb-Associated Non-Coding RNAs. JD497214 - Sequence 478238 from Patent EP1572962. JD024595 - Sequence 5619 from Patent EP1572962. LF350876 - JP 2014500723-A/158379: Polycomb-Associated Non-Coding RNAs. MA586453 - JP 2018138019-A/158379: Polycomb-Associated Non-Coding RNAs. JD411168 - Sequence 392192 from Patent EP1572962. LF350877 - JP 2014500723-A/158380: Polycomb-Associated Non-Coding RNAs. MA586454 - JP 2018138019-A/158380: Polycomb-Associated Non-Coding RNAs. AF088185 - Homo sapiens guanine nucleotide-binding protein Gs alpha subunit isoform L3 mRNA, complete cds. JD185607 - Sequence 166631 from Patent EP1572962. LF350878 - JP 2014500723-A/158381: Polycomb-Associated Non-Coding RNAs. MA586455 - JP 2018138019-A/158381: Polycomb-Associated Non-Coding RNAs. JD211591 - Sequence 192615 from Patent EP1572962. LF350879 - JP 2014500723-A/158382: Polycomb-Associated Non-Coding RNAs. MA586456 - JP 2018138019-A/158382: Polycomb-Associated Non-Coding RNAs. JD347865 - Sequence 328889 from Patent EP1572962. JD359538 - Sequence 340562 from Patent EP1572962. JD389681 - Sequence 370705 from Patent EP1572962. JD389682 - Sequence 370706 from Patent EP1572962. LF350880 - JP 2014500723-A/158383: Polycomb-Associated Non-Coding RNAs. MA586457 - JP 2018138019-A/158383: Polycomb-Associated Non-Coding RNAs. JD303514 - Sequence 284538 from Patent EP1572962. LF350881 - JP 2014500723-A/158384: Polycomb-Associated Non-Coding RNAs. MA586458 - JP 2018138019-A/158384: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_chrebpPathway - ChREBP regulation by carbohydrates and cAMP h_erkPathway - Erk1/Erk2 Mapk Signaling pathway h_gcrPathway - Corticosteroids and cardioprotection h_bArrestin-srcPathway - Roles of ¿-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling h_bArrestinPathway - ¿-arrestins in GPCR Desensitization h_raccPathway - Ion Channels and Their Functional Role in Vascular Endothelium h_agpcrPathway - Attenuation of GPCR Signaling h_barr-mapkPathway - Role of ¿-arrestins in the activation and targeting of MAP kinases h_CCR3Pathway - CCR3 signaling in Eosinophils
Reactome (by CSHL, EBI, and GO)
Protein Q5JWF2 (Reactome details) participates in the following event(s):
R-HSA-751013 Inactive G alpha (s) reassociates with G beta:gamma R-HSA-164381 G alpha (s) auto-inactivates by hydrolysing GTP to GDP R-HSA-163617 G alpha (s) activates adenylate cyclase R-HSA-381704 G(s):GTP activates Adenylyl cyclase R-HSA-392874 Dissociation of the Prostacyclin receptor:Gs complex R-HSA-422320 Heterotrimeric G(s) complex dissociates R-HSA-744886 The Ligand:GPCR:Gs complex dissociates R-HSA-825631 Glucagon:GCGR mediates GTP-GDP exchange R-HSA-392852 Activated prostacyclin receptor binds G-protein Gs R-HSA-744887 Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs R-HSA-381706 GLP-1R:GLP-1 activates G(s) R-HSA-381612 Glucagon-like Peptide-1 Receptor (GLP1R) binds Glucagon-like peptide-1 R-HSA-432188 AVP:AVPR2 Complex binds inactive heterotrimeric G(s) complex R-HSA-392870 Gs activation by prostacyclin receptor R-HSA-379044 Liganded Gs-activating GPCR acts as a GEF for Gs R-HSA-432195 AVP:AVPR2:heterotrimeric G(s) complex exchanges GDP for GTP R-HSA-164377 Activated Adenylate cyclase catalyses cAMP synthesis R-HSA-381607 Activated Adenylyl cyclase synthesizes cyclic AMP R-HSA-418555 G alpha (s) signalling events R-HSA-163359 Glucagon signaling in metabolic regulation R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-HSA-392851 Prostacyclin signalling through prostacyclin receptor R-HSA-420092 Glucagon-type ligand receptors R-HSA-388396 GPCR downstream signalling R-HSA-163685 Energy Metabolism R-HSA-445717 Aquaporin-mediated transport R-HSA-422356 Regulation of insulin secretion R-HSA-418346 Platelet homeostasis R-HSA-373080 Class B/2 (Secretin family receptors) R-HSA-372790 Signaling by GPCR R-HSA-164378 PKA activation in glucagon signalling R-HSA-1430728 Metabolism R-HSA-382551 Transport of small molecules R-HSA-109582 Hemostasis R-HSA-500792 GPCR ligand binding R-HSA-162582 Signal Transduction
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