Genomic imprinting

Gene: GNAS

The mode of inheritance of this gene should ideally be set to both MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) AND MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) since the gene has both paternally and maternally imprinted transcripts. However, this is not currently possible in PanelApp.

With the current mode of inheritance of MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown variants in imprinted transcripts will only be tiered under the 'incomplete penetrance' mode.

We are currently looking at the best options for updating the mode of inheritance to cover the maternal and paternal imprinting seen in this gene.

Created: 17 Apr 2026, 12:08 p.m. | Last Modified: 17 Apr 2026, 12:08 p.m.

Panel Version: 0.157

I don't know

Comment on mode of inheritance: Differential expression of the different GNAS transcripts:
• Gs-alpha transcript (α-subunit of G protein)
o Not imprinted (non-methylated) - biallelic expression, except:
 renal proximal tubules, thyroid, gonads, pituitary – maternally expressed
o Nearly all tissues - ubiquitously expressed
• XLAS
o paternally expressed
o promoter in DMRs
o neuroendocrine tissues and the nervous system
o promoter in DMRs
• NESP55
o maternally expressed
o promoter in DMRs
• A/B transcript
o paternally expressed
o ubiquitously expressed
o noncoding transcript
o promoter in DMRs
• antisense GNAS transcript (GNASAS)
o paternally expressed
o ubiquitously expressed
o noncoding transcript
o promoter in DMRs

Created: 11 Oct 2022, 3:11 p.m. | Last Modified: 11 Oct 2022, 3:11 p.m.

Panel Version: 0.146

Comment on phenotypes: Pseudohypoparathyroidism Ia, OMIM:103580, Pseudohypoparathyroidism Ib, OMIM:603233 & Pseudohypoparathyroidism Ic, OMIM:612462 are all caused by maternally-inherited GNAS1 variants. Osseous heteroplasia, progressive, OMIM:166350 & Pseudopseudohypoparathyroidism, OMIM:612463 are caused by paternally-inherited GNAS1 variants

Created: 18 Jan 2022, 12:22 p.m. | Last Modified: 18 Jan 2022, 12:22 p.m.

Panel Version: 0.105

GNAS complex locus includes: NESP55, GNASXL, Exon-1A (STX16), GS-alpha listed in supplimentary table (PMID 30794780)HGNC::4392)

Created: 22 Dec 2020, 6:10 p.m. | Last Modified: 4 Jan 2021, 3:15 p.m.

Panel Version: 0.26

the regulatory region of GNAS is >100kb and includes elements subject to parent-of-origin specific regulation. Indels and rearrangements of the region are well-established causes of disease, associated in some but not all cases with alterations of DNA methylation marks.http://omim.org/entry/139320?search=gnas&highlight=gnas. This is (a) gene in imprinted regions, in which point mutations / indels are associated with disease (e.g. CDKN1C); (b) gene for which alteration of effective copy number is associated with disease (though mutations in the transcript are currently not identified).

Created: 4 May 2017, 2:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)

Phenotypes
From the Craniosynostosis syndromes phenotypes gene panel