ArticleGenome biology2023
A comprehensive map of human glucokinase variant activity.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 54 citations in OpenAlex.
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- Proteome-wide prediction of the functional impact of missense variants with ProteoCast.Nature communications · 2026Article
- Determining the intra-residue correlation of missense variant impact using MAVE scores: implications for the ACMG/AMP PM5 criterion for DNA variant classification.Genome medicine · 2026Article
- The functional landscape of coding variation in the familial hypercholesterolemia geneScience (New York, N.Y.) · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Modelling the effects of human SUR1 R1420H variation on insulin secretory function using isogenic iPSC-derived pancreatic islets.Diabetologia · 2026Article
- Personalized management of glucokinase-related monogenic diabetes (GCK-MODY) during pregnancy: a case report.Frontiers in endocrinology · 2026Article
- Rosace-AA: enhancing interpretation of deep mutational scanning data with amino acid substitution and position-specific insights.Bioinformatics advances · 2026Article
- Article
- Functional Characterization of Glucokinase Variants to Aid Clinical Interpretation of Monogenic Diabetes.International journal of molecular sciences · 2025Article
- MaveMD: A functional data resource for genomic medicine.medRxiv : the preprint server for health sciences · 2025Article
- GC-MS profiling and computational analysis of Balanites aegyptiaca phytoconstituents for antidiabetic activity: insights from network pharmacology and molecular docking.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A probabilistic graphical model for estimating selection coefficients of nonsynonymous variants from human population sequence data.Nature communications · 2025Article
- Variant effect predictor correlation with functional assays is reflective of clinical classification performance.Genome biology · 2025Article
- Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.Biomolecules · 2025Review
- Multi-ancestry genome-wide association analyses: a comparison of meta- and mega-analyses in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.BMC genomics · 2025Article
- Molecular Docking, Pharmacophore Modeling and ADMET Prediction of Novel Heterocyclic Leads as Glucokinase Activators.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2025Article
- Case Report: New insights about clinical manifestations of patients withFrontiers in endocrinology · 2025Article
- Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes.Communications medicine · 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
15 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundGlucokinase (GCK) regulates insulin secretion to maintain appropriate blood glucose levels. Sequence variants can alter GCK activity to cause hyperinsulinemic hypoglycemia or hyperglycemia associated with GCK-maturity-onset diabetes of the young (GCK-MODY), collectively affecting up to 10 million people worldwide. Patients with GCK-MODY are frequently misdiagnosed and treated unnecessarily. Genetic testing can prevent this but is hampered by the challenge of interpreting novel missense variants.
resultHere, we exploit a multiplexed yeast complementation assay to measure both hyper- and hypoactive GCK variation, capturing 97% of all possible missense and nonsense variants. Activity scores correlate with in vitro catalytic efficiency, fasting glucose levels in carriers of GCK variants and with evolutionary conservation. Hypoactive variants are concentrated at buried positions, near the active site, and at a region of known importance for GCK conformational dynamics. Some hyperactive variants shift the conformational equilibrium towards the active state through a relative destabilization of the inactive conformation.
conclusionOur comprehensive assessment of GCK variant activity promises to facilitate variant interpretation and diagnosis, expand our mechanistic understanding of hyperactive variants, and inform development of therapeutics targeting GCK.
Indexed as
Identifiers
What Socratic 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 Socratic graph.