The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


Detailed entry for Gene:

(see also, Gnasxl, Nesp)


Human Chr20q13.2-q13.3
Mouse Chr2 (distal)


OMIM   Human Entry for GNAS


GNAS1 is variably imprinted in humans (Hayward BE et al, 1998; Hayward BE et al, 1998); and other transcripts in the complex GNAS1 locus are also imprinted (see Nesp, Gnasxl). The expressivity of GNAS1 mutations depends on parent-of-origin and the murine Gs-alpha locus is imprinted based on knockout experiments (Yu S et al, 2001; Yu S et al, 2000; Yu S et al, 1998).

Gene Product:

Gnas1 encodes the alpha subunit of a major heterotrimeric Gs signaling protein. However, the Gnas1 locus is complex, with multiple gene products derived from alternative promoters, alternative splicing and alternative reading frames (see Gnasxl, Nesp); reviewed in (Lalande M, 2001).

Functional Data:

The Gs-alpha subunit is a component of the heterotrimeric stimulatory G-protein that couples multiple hormone receptors (parathyroid hormone receptor and others) to adenylyl cyclase. The associated human genetic disorders are complex: GNAS1 mutations (maternal transmission) in pseudo-hypoparathyroidism type Ia (PHP-Ia); in contrast, pseudo-pseudo-hypoparathyroidism (PPHP) is seen with paternal transmission of GNAS1 mutations. Albright hereditary osteodystrophy is a more general syndrome, seen with either type of transmission of GNAS1 mutations (Lalande M, 2001; Weinstein LS et al, 1999). Gs-alpha knockout mice show an imprinted phenotype, with increased insulin-sensitivity and adipocyte hypertrophy in the null animals (Yu S et al, 2001; Yu S et al, 2000; Yu S et al, 1998). Mice with MatDp2 affecting the distal region containing Gnas are hypoactive and die within a few hours of birth; mice with PatDp2 are hyperactive and survive for several days after birth, but the responsible gene(s) are not known; see (Williamson CM et al, 1998) and references therein.


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