ArticleNature communications2026
The genetic architecture of an allosteric hormone receptor.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed.
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- The genetic architecture of an allosteric hormone receptor.Nature communications · 2026Article
- Allosteric and energetic remodeling of a PDZ domain by protein domain extensions.Nature communications · 2026Article
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.
Funding
Abstract
Many proteins function as switches, transducing the concentrations of environmental chemicals into cellular responses. It is not well understood how signal processing by switches is genetically encoded. Here, using a massively parallel approach, GluePCA, we present >40,000 measurements and a complete map of how mutations alter the quantitative activation function of a receptor switch, the plant hormone sensor PYL1. Close to 90% of missense variants tune the dose-response of the receptor, often causing correlated changes in sensitivity, basal activity, maximum response and induction steepness. Based on theory we predict and then validate the underlying latent mechanism as a change in protein stability. Beyond this, signalling parameters can be independently tuned, with large effects in interface-distal positions and a modular genetic architecture across the receptor's structure. Rare single amino acid substitutions confer phenotypic innovation, including inverted and band-stop activation functions. Our data demonstrate the feasibility of dose-response profile quantification at massive scale and reveal the remarkable evolutionary malleability of a protein switch.
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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 Socratic graph.