GNAS

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GNAS

A locus on chromosome 20q13.3 that has a highly complex imprinted expression pattern, giving rise to maternally, paternally and biallelically expressed transcripts derived from four alternative promoters and 5' exons. Some transcripts have a differentially methylated region (DMR) at their 5' exons. This DMR is commonly found in imprinted genes and correlates with transcript expression; one transcript produced from this locus and the antisense transcript are paternally expressed, noncoding RNAs, which may regulate regional imprinting. Alternative splicing of downstream exons results in different forms of the stimulatory G-protein alpha subunit, a key component of the classical signal-transduction pathway linking receptor-ligand interactions to adenylyl cyclase activation and various cellular responses.

Molecular pathology
GNAS mutations have been linked to pseudohypoparathyroidism types 1a and 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone and pituitary tumours.
References in periodicals archive ?
PHP-1b results from changes in methylation that occur at the GNAS complex locus (GNAS) (2).
[4] Nonstandard abbreviations: PTH, parathyroid hormone; PHP, pseudohypoparathyroidism; RI, reference interval; AHO, Albright hereditary osteodystrophy; GNAS, GNAS complex locus; NESP55, neuroendocrine secretory protein-55.
The GNAS complex locus and human diseases associated with loss-of-function mutations or epimutations within this imprinted gene.
The GNAS complex locus encodes the alpha-subunit of the stimulatory G protein (Gs[alpha]), a ubiquitous signaling protein mediating the actions of many hormones, and gives rise to other gene products, most of which exhibit exclusively monoallelic expression.
The most common somatic mutations identified were in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes.
[9] Human genes: JAK3, Janus kinase 3; KRAS, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; GNAS, GNAS complex locus; AKT1, v-akt murine thymoma viral oncogene homolog 1; APC, adenomatous polyposis coli; MET, met protooncogene; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase; RB1, retinoblastoma 1; STK11, serine/threonine kinase 11; TP53, tumor protein p53; SMAD4, SMAD family member 4; ATM, ataxia telangiectasia mutated; IDH1, isocitrate dehydrogenase 1 (NADP+); NRAS, neuroblastoma RAS viral (v-ras) oncogene homolog.
As a proof of principle, the authors correctly detected trisomy 21 by assessing the methylation density of chromosome 21 and correctly deduced the imprinting status of 4 selected loci: H19 [2] [H19, imprinted maternally expressed transcript (non-protein coding)], KCNQ1OT1 [KCNQ1 opposite strand/antisense transcript 1 (non-protein coding)], MEST (mesoderm specific transcript), and GNAS (GNAS complex locus).
[2] Human genes: H19, H19, imprinted maternally expressed transcript (non-protein coding); KCNQ10T1, KCNQ1 opposite strand/antisense transcript 1 (non-protein coding); MEST, mesoderm specific transcript; GNAS, GNAS complex locus; ST0X1, storkhead box 1.
Four loci fulfilled the criteria: H19 [5] [HI9, imprinted maternally expressed transcript (non-protein coding)], KCNQIOTl [KCNQ1 opposite strand/antisense transcript 1 (non-protein coding)], MEST (mesoderm specific transcript), and GNAS (GNAS complex locus).