Mutations in the Gs alpha gene causing hormone resistance

Giovanna Mantovani, Anna Spada

Research output: Contribution to journalArticlepeer-review


G-protein-coupled receptors (GPCRs) and G proteins mediate the effects of a number of hormones of relevance to endocrinology. Genes encoding these molecules may be targets of loss- or gain-of-function mutations, resulting in endocrine disorders. The only mutational change of G proteins so far unequivocally associated with endocrine disorders occurs in the Gsα gene (GNAS1, guanine nucleotide binding protein α stimulating activity polypeptide 1), which activates cyclic AMP (cAMP)-dependent pathways. Heterozygous loss-of-function mutations of GNAS1 in the active maternal allele cause resistance to hormones acting through Gsα-coupled GPCRs, whereas somatic gain-of-function mutations cause proliferation of endocrine cells recognizing cAMP as mitogen. This review will focus on inactivating mutations leading to hormone resistance syndromes, i.e., pseudohypoparathyroidism types Ia and Ib.

Original languageEnglish
Pages (from-to)501-513
Number of pages13
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Issue number4
Publication statusPublished - Dec 2006


  • Albright's osteodystrophy
  • GNAS1
  • imprinting
  • pseudohypoparathyroidism

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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