GNAS2_HUMAN
Source:
PM19886704
BSc_CH
Marked as 'Membrane associated protein'
Confidence:
medium (present in either hRBCD or BSc_CH or PM22954596)
Search PubMed for
(RBC AND this entry)
Gene names:
GNAS
, GNAS1, GSP
Protein names and data:
GNAS2_HUMAN
, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
, Adenylate cyclase-stimulating G alpha protein
Lenght: 394 a.a.
Mass: 45665 Da
fasta formatted sequence
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. Stimulates the Ras signaling pathway via RAPGEF2.
Disease:
( OMIM:
102200
103580
139320
166350
174800
219080
603233
612462
)
Albright hereditary osteodystrophy (AHO) [MIM:103580]: A disorder characterized by short stature, obesity, round facies, brachydactyly and subcutaneous calcification. It is often associated with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels. Note=The disease is caused by mutations affecting the gene represented in this entry. Pseudohypoparathyroidism 1A (PHP1A) [MIM:103580]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry. McCune-Albright syndrome (MAS) [MIM:174800]: Characterized by polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The mutations producing MAS lead to constitutive activation of GS alpha. Note=The disease is caused by mutations affecting the gene represented in this entry. Growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]: Pituitary adenomas include somatotropinoma and prolactinoma. Note=The disease is caused by mutations affecting the gene represented in this entry. Progressive osseous heteroplasia (POH) [MIM:166350]: Rare autosomal dominant disorder characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue. Note=The disease is caused by mutations affecting the gene represented in this entry. ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]: 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 truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Note=The disease is caused by mutations affecting the gene represented in this entry. Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH. Note=The disease is caused by mutations affecting the gene represented in this entry. 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. 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. Note=The disease is caused by mutations affecting the gene represented in this entry. Pseudohypoparathyroidism 1C (PHP1C) [MIM:612462]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Cellular location:
Cell membrane; Lipid-anchor (By similarity).
Genetic variants
99 - 99
L -> P (in AHO). VAR_003439
106 - 106
I -> S (in AHO/PHP1A). VAR_031872
115 - 115
P -> L (in AHO). VAR_017843
156 - 156
D -> N (in PHP1A). VAR_031873
159 - 159
V -> M (in PHP1A). VAR_031874
165 - 165
R -> C (in AHO). VAR_003440
201 - 201
R -> C (in MAS and somatotrophinoma; dbSNP:rs11554273). VAR_003442
11554273
201 - 201
R -> G (in MAS). VAR_017844
201 - 201
R -> H (in MAS, somatotrophinoma and AIMAH). VAR_003441
201 - 201
R -> L (in non-MAS endocrine tumors). VAR_017845
201 - 201
R -> S (in AIMAH, pituitary tumor and polyostotic fibrous dysplasia). VAR_017846
227 - 227
Q -> H (in pituitary adenoma; ACTH- secreting adenoma; in a patient with severe Cushing syndrome complicated by psychosis). VAR_017847
227 - 227
Q -> R (in somatotrophinoma). VAR_003443
231 - 231
R -> H (in AHO; impairs the ability to mediate hormonal stimulation). VAR_017848
242 - 242
T -> I (in AHO). VAR_031875
246 - 246
F -> S (in AHO). VAR_031876
250 - 250
S -> R (in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function). VAR_017849
258 - 258
R -> W (in AHO; defective GDP binding resulting in increased thermolability and decreased activation). VAR_015388
259 - 259
E -> V (in AHO). VAR_031877
280 - 280
R -> G (in PHP1A). VAR_031878
280 - 280
R -> K (in PHP1A). VAR_031879
281 - 281
W -> R (in POH). VAR_031880
338 - 338
K -> N (in PHP1A). VAR_031881
366 - 366
A -> S (in AHO; paradoxical combination of AHO and testotoxicosis; constitutively activates adenylyl cyclase in vitro; accounts for the testotoxicosis phenotype; mutant form is quite stable at testis temperature; rapidly degraded at 37 degrees explaining the AHO phenotype caused by loss of Gs activity). VAR_017850
380 - 380
R -> L (in dbSNP:rs8986). VAR_049358
8986
382 - 382
Missing (unable to interact with the receptor for PTH). VAR_034744
385 - 385
R -> H (in AHO; uncouples receptors from adenylyl cyclases). VAR_003444
388 - 388
L -> R (in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation). VAR_066387
392 - 392
E -> K (in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation). VAR_066388
Database cross-references
UniProt:
P63092
Ensembl:
ENST00000265620
Ensembl:
ENST00000306090
Ensembl:
ENST00000354359
Ensembl:
ENST00000371085
Ensembl:
ENST00000371095
MIM:
102200
MIM:
103580
MIM:
139320
MIM:
166350
MIM:
174800
MIM:
219080
MIM:
603233
MIM:
612462
neXtProt:
NX_P63092
Antibodypedia:
P63092
(may not find the protein thus also not any antibody)
Local full text data:
click here
Users' comments
Login to add a comment.