ArticleCell2018
Disease-Causing Mutations in the G Protein Gαs Subvert the Roles of GDP and GTP.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Efficacy of antiresorptive agents in fibrous dysplasia and McCune Albright syndrome, a systematic review and meta-analysis.Reviews in endocrine & metabolic disorders · 2023Pooled it
- Structural basis of stepwise G protein activation by the viral chemokine receptor US28.bioRxiv : the preprint server for biology · 2026Article
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Review
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.EMBO molecular medicine · 2025Review
- Fibrous dysplasia/McCune-Albright syndrome: state-of-the-art advances, pathogenesis, and basic/translational research.Orphanet journal of rare diseases · 2025Review
- Proteome-wide assessment of differential missense variant clustering in neurodevelopmental disorders and cancer.Cell genomics · 2025Article
- Contract to kill: GNAS mutation.Molecular cancer · 2025Review
- Structure and function of a near fully-activated intermediate GPCR-Gαβγ complex.Nature communications · 2025Article
- Characterisation of aEndocrine oncology (Bristol, England) · 2025Article
- Grading and staging for pituitary neuroendocrine tumors.Brain pathology (Zurich, Switzerland) · 2025Review
- Molecular and Clinicopathologic Impact of GNAS Variants Across Solid Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Mechanistic insights into G-protein coupling with an agonist-bound G-protein-coupled receptor.Nature structural & molecular biology · 2024Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.NPJ systems biology and applications · 2024Article
- Structure and function of a ligand-free GPCR-Gαβγ intermediate complex.Research square · 2024Article
- Inhibition of adenylyl cyclase by GTPase-deficient GαCell communication and signaling : CCS · 2024Article
- KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance.Current oncology (Toronto, Ont.) · 2024Review
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.Cell · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The single most frequent cancer-causing mutation across all heterotrimeric G proteins is R201C in Gαs. The current model explaining the gain-of-function activity of the R201 mutations is through the loss of GTPase activity and resulting inability to switch off to the GDP state. Here, we find that the R201C mutation can bypass the need for GTP binding by directly activating GDP-bound Gαs through stabilization of an intramolecular hydrogen bond network. Having found that a gain-of-function mutation can convert GDP into an activator, we postulated that a reciprocal mutation might disrupt the normal role of GTP. Indeed, we found R228C, a loss-of-function mutation in Gαs that causes pseudohypoparathyroidism type 1a (PHP-Ia), compromised the adenylyl cyclase-activating activity of Gαs bound to a non-hydrolyzable GTP analog. These findings show that disease-causing mutations in Gαs can subvert the canonical roles of GDP and GTP, providing new insights into the regulation mechanism of G proteins.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.