GNAS complex locus
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GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit (Gs-α), a key component of many signal transduction pathways.
This gene locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contains a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript exists, and this antisense transcript and one of the transcripts are paternally expressed, produce noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping open reading frame, which encodes a structurally unrelated protein, called ALEX.
The GNAS locus is imprinted and encodes 5 main transcripts:
- A/B transcript
- antisense GNAS transcript
Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (Gs-α), a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular responses. Multiple transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined.
Mutations are associated with:
- Albright hereditary osteodystrophy
- pseudohypoparathyroidism type Ia
- pseudohypoparathyroidism type Ib
- McCune-Albright syndrome
Mutations in this gene also result in progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors.
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