GNAS
MIM.139320 20q13.2
Guanine nucleotide-binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins.
The activity of hormone-sensitive adenylate cyclase is regulated by at least 2 G proteins, 1 stimulatory (Gs) and 1 inhibitory (Gi) (MIM.139310). A third G protein, Go (MIM.139311), is abundant in brain.
Each G protein is a heterotrimer composed of an alpha, beta, and gamma subunit. The GNAS1 gene encodes the alpha subunit of the G stimulatory protein Gs.
Neuroendocrine secretory protein-55 (NESP-55), the latest addition to the chromogranin family, is a product of a genomically imprinted gene transcribed exclusively from the maternal allele.
Expression in tumors
pheochromocytoma
pancreatic endocrine tumors
neuroblastomas (50%) (#12771991#)
Pathology
heterozygous deactivating GNAS1 mutations in Albright hereditary osteodystrophy (AHO)
- Maternally derived mutations are usually associated with resistance to parathyroid hormone termed "pseudohypoparathyroidism type Ia."
- Paternally derived mutations are associated with AHO but usually normal hormone responsiveness, known as "pseudo-pseudohypoparathyroidism."
mutations in fibrous dysplasia
liposclerosing myxofibrous tumor (#14652823#)
mutations of GNAS1
- Albright hereditary osteodystrophy
- pseudohypoparathyroidism type Ia (PHP Ia) vpseudopseudohypoparathyroidism (PPHP)
- pituitary tumors
- fibrous dysplasia
- liposclerosing myxofibrous tumor
- unilateral macro-orchidism without sexual precocity in McCune-Albright syndrome (#17101633#, #16462147#)
Références
Unexpected mosaicism of R201H-GNAS1 mutant-bearing cells in the testes underlie macro-orchidism without sexual precocity in McCune-Albright syndrome. Rey RA, Venara M, Coutant R, Trabut JB, Rouleau S, Lahlou N, Sultan C, Limal JM, Picard JY, Lumbroso S. Hum Mol Genet. 2006 Dec 15;15(24):3538-43.PMID: #17101633#
McCune-Albright syndrome in a boy may present with a monolateral macroorchidism as an early and isolated clinical manifestation. Arrigo T, Pirazzoli P, De Sanctis L, Leone O, Wasniewska M, Messina MF, De Luca F. Horm Res. 2006;65(3):114-9. PMID: #16462147#
Srivastava A, Padilla O, Fischer-Colbrie R, Tischler AS, Dayal Y. Neuroendocrine secretory protein-55 (NESP-55) expression discriminates pancreatic endocrine tumors and pheochromocytomas from gastrointestinal and pulmonary carcinoids. Am J Surg Pathol. 2004 Oct;28(10):1371-8. PMID: #15371954#