Taxon:

Human

Gene:

GNAS complex locus (GNAS1, Gs alpha, NESP55, XLalpha s, GNAS1-AS(SANG), miR-296, miR-298)

Chromosome:

20

Location:

20q13.2

Description:

The GNAS1 gene contains three imprinted protein-coding transcripts, one non-coding transcript and one imprinted antisense transcript.
1. Gs-alpha (a small GTPases) is maternally expressed the pituitary gland (Hayward BE et al, 2001), thyroid and gonads (Mantovani G et al. 2002; Liu J et al, 2003; Germain-Lee EL et al, 2002), but is biallelically expressed in most other tissues (Hayward BE et al, Aug 1998). It is likely to be imprinted in the renal proximal tubules (Liu J et al, 2000). In clones derived from bone marrow stroma, non-imprinted allelic imbalance was noted in the Gs alpha transcript (Michienzi S et al, 2007).
2. XLalpha s (the extra-large variant of the G protein alpha-subunit) is paternally expressed (Hayward BE et al, Aug 1998). Multiple transcripts and protein isoforms are derived from the XL (XXL) promoter (Abramowitz J et al, 2004).
3. NESP55 (Neuroendocrine secretory protein 55, a chromogranin-like protein) is maternally expressed in multiple fetal tissues (Hayward BE et al, Dec 1998).
4. The exon 1A (exon A/B) transcript is probably not translated and is paternally expressed (Liu J et al, 2000).
5. GNAS1-AS(SANG) is a paternally expressed antisense transcript that spans the upstream NESP55 region (Hayward BE et al, 2000).
This transcript hosts two microRNAs. Robson, JE et al, (2012) provided evidence for exclusive paternal expression of miR-296-5p and miR-298 in two lymphoblastoid human cell lines.

The inheritance pattern of several diseases suggested imprinting of the GNAS1 gene . Albright hereditary osteodystrophy displays various physical abnormalities as well as end organ resistance to various hormones including parathyroid (pseudo-hypoparathyroidism type 1a) when inherited maternally (60 offspring from 33/36 maternal transmitting parents). However when this disease is transmitted paternally, offspring (6) suffer from the physical features of AHO but lack hormone resistance (pseudopseudo-hypoparathyroidism) (Davies SJ et al, 1993). Recent evidence that the Gs-alpha transcript is predominantly maternally expressed in the thyroid gland and gonads is consistent with this inheritance pattern (Mantovani G et al. 2002). Progressive osseous heteroplasia is attributable to paternally inherited mutations of GNAS1 (Shore EM et al, 2002). Abnormal imprinting (loss of methylation) of a region upstream of the Gs alpha promoter in exon 1A (exon A/B) has been identified in 13 of 13 patients with pseudohypoparathyroidism type IB (renal resistance to parathyroid hormone lacking other AHO associated symptoms) (Liu J et al, 2000; Bastepe M et al, 2001). Pseudohypoparathyroidism type IB shows an imprinted inheritance pattern, ie, the disease is always maternally transmitted (Juppner H et al, 1998).
For review summaries see Lalande M, 2001 and Weinstein LS et al, 2002.

Category:

Imprinted genes

Record:

56

Last Modified 8/3/2017

Links:

Gene  OMIM   Detailed Entry


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