Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences

The Catalogue for Transmission Genetics in Arabs CTGA Database

GNAS Complex Locus

Alternative Names adenylate cyclase enzyme. As adenylate cyclase is GNAS believed to play a key role in signaling pathways GNAS1 Gene, Formerly that help regulate osteogenesis and hormone GNAS1, Formerly production, the is essential for the Guanine Nucleotide-Binding Protein, Alpha- regulation of these processes. Stimulating Activity Polypeptide 1, Gs, Alpha Subunit The gene is associated with several disorders, Stimulatory G Protein namely: somatic acromegaly, ACTH-independent Adenylate Cyclase Stimulatory Protein, Alpha macronodular adrenal hyperplasia, somatic mosaic Subunit McCune-Albright syndrome, progressive osseous Secretogranin VI heteroplasia, (types Ia, Neuroendocrine Secretory Protein 55 Ib and Ic) and pseudopseudohypoparathyroidism. NESP55 XL-Alpha-S Molecular Genetics XLAS The GNAS gene, located on the long arm of A/B Transcript 20, spans a length of 71.4 kb. Its Alternative Gene Product Encoded by The XL coding sequence is spread across 22 exons and it Exon encodes a 28 kDa protein product made up of 245 ALEX amino acids. GNAS is a complex imprinted locus and the presence of alternative promoters as well as Record Category alternative splicing results in multiple isoforms of Gene locus the protein. The Gs-alpha transcript, responsible for encoding the alpha subunit of the stimulatory WHO-ICD guanine nucleotide-binding protein, is expressed N/A to gene loci biallelically in most tissues of the body. The remaining GNAS transcripts are all expressed Incidence per 100,000 Live Births exclusively from either the paternal or maternal N/A to gene loci allele. Inactivating loss-of-function mutations in the GNAS1 gene result in pseudohypoparathyroidism OMIM Number Ia, pseudopseudohypoparathyroidism and 139320 progressive osseous heteroplasia, while activating gain-of-function mutations in the GNAS1 gene Mode of Inheritance result in McCune-Albright syndrome, polyostotic N/A to gene loci fibrous dysplasia and various endocrine tumors.

Gene Map Locus Epidemiology in the Arab World 20q13.32 Saudi Arabia Anazi et al. (2016) attempted to study the Description effectiveness of genomic tools in the diagnosis of The GNAS gene encodes the stimulatory alpha Intellectual Disability (ID) cases. 337 ID patients subunit of a protein complex called a guanine were subjected to molecular karyotyping, exome nucleotide-binding protein (G protein). G proteins sequencing or sequencing by a gene panel are involved in , the process of comprised of neurologically associated genes. transmitting signals from a variety of stimuli Genomic tools were found to have a higher outside a cell to its interior. The G protein diagnostic yield than standard clinical evaluations containing the GNAS encoded subunit is (58% vs 16%). In one patient, the analysis helped responsible for stimulating the activity of the uncover a de novo mutation (c.2405T>C,

Copyright © Centre for Arab Genomic Studies 1 p.Val802Ala) in the GNAS gene. It was further Altassan N, Arold ST, Abouelhoda M, Wakil SM, noted that the patient presented atypical features not Monies D, Shaheen R, Alkuraya FS. Clinical consistent with a GNAS phenotype such as metopic genomics expands the morbid genome of craniosynostosis, hydronephrosis, brain heterotopia, intellectual disability and offers a high diagnostic thinning of corpus callosum and thyroid agenesis. yield. Mol Psychiatry. 2016 Jul 19. PMID: 27431290. References Anazi S, Maddirevula S, Faqeih E, Alsedairy H, Related CTGA Records Alzahrani F, Shamseldin HE, Patel N, Hashem M, McCune-Albright Syndrome (OMIM 174800) Ibrahim N, Abdulwahab F, Ewida N, Alsaif HS, Al Sharif H, Alamoudi W, Kentab A, Bashiri FA, External Links Alnaser M, AlWadei AH, Alfadhel M, Eyaid W, http://www.genecards.org/cgi- Hashem A, Al Asmari A, Saleh MM, AlSaman A, bin/carddisp.pl?gene=GNAS Alhasan KA, Alsughayir M, Al Shammari M, Mahmoud A, Al-Hassnan ZN, Al-Husain M, Contributors Osama Khalil R, Abd El Meguid N, Masri A, Ali R, Sayeeda Hana Ben-Omran T, El Fishway P, Hashish A, Ercan 26.01.2017 Sencicek A, State M, Alazami AM, Salih MA,

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