GNAS

(redirected from NESP55)

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 ?
The autosomal dominant form most commonly occurs as result of microdeletions in STX16, the gene encoding syntaxin 16, while the sporadic form has predilection to GNAS microdeletions involving exon NESP55 (6,7).
[4] Nonstandard abbreviations: PTH, parathyroid hormone; PHP, pseudohypoparathyroidism; RI, reference interval; AHO, Albright hereditary osteodystrophy; GNAS, GNAS complex locus; NESP55, neuroendocrine secretory protein-55.
Chromogranin A is a 439-residue-long glycoprotein [15,16], a member of a larger family of soluble secretory proteins (granin proteins) that includes also chromogranin B (CgB), secretogranin (Sg) II (CgC), Sg III (1B1075), Sg IV (HISL-19), Sg V (7B2) and Sg VI (NESP55), Sg VII (VGF), and Sg VIII (proSAAS) [12], localized in secretory granules of neuroendocrine cells, neurons, and the adrenal medulla [17].
GNAS is an imprinted gene which gives rise to multiple gene products, including transcripts that encode the a-subunit of the stimulatory guanine nucleotide-binding protein (G protein) (Gs[alpha]), extra-large Gs[alpha] (XL[alpha]s), and neuroendocrine secretory protein 55 (NESP55), as well as to noncoding A/B (also referred to as 1A) and antisense transcripts (GNAS-AS1).
Other GNAS transcripts NESP55, XL[alpha]s, and A/B, with the exception of GNAS-AS1 consists of distinct exons, and all contain their own, differentially methylated, unique first exons (DMRs), which are spliced onto exon 2 of GNAS.
iPPSD3: Methylation change(s) at one or more GNAS DMRs, associated with or without a genetic deletion (STX16, NESP55, AS etc.) or cytogenetic (UPD) defect.
IMP3, NESP55, TTF-1 and CDX2 serve as an immunohistochemical panel in the distinction among small-cell carcinoma, gastrointestinal carcinoid, and pancreatic endocrine tumor metastasized to the liver.
Of these genes, only 10 genes have been reported to show imprinting in sheep (GTL2, DLK1, DAT, PEG11, antiPEG11, MEG8, MEST, IGF2, H19 and IGF2r; Killian et al., 2001), 8 in cattle (IGF2r, XIST, IGF2, GTL2, NESP55, H19, PEG3 and NNAT) and 3 in pigs (IGF2, IGF2r, and IGF2-AS, DLK1; University of Otago, 2006; Li et al., 2008).